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Welcome to the Renal Cell
Carcinoma File
Patients all over the world
have used the information in The Renal Cell Carcinoma File since
1992, when the Center for Current Researchone of the first
80 companies on the Internetwas founded. Our highly trained
researchers (all of whom hold Ph.D.s) have searched the advanced
medical database at the National Library of Medicine and compiled
a comprehensive collection of research descriptions on Renal
Cell Carcinoma and its care.
As you will see, the following research descriptions detail the
findings published in the most respected journals in the field.
Because the research descriptions are written in medical terms,
most people will bring all or parts of the Renal Cell Carcinoma
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you need it.
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hope the information fosters better health.
Sincerely,
Gregory A. Fraser, Ph.D.
Director of Research
Important Note: The following information
is provided for your education. It should not be relied upon for
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Previous Renal Cell Carcinoma
Research: 2002-2006
The
Renal Cell Carcinoma
File also contains summaries of past
research that has shown promise and may still be standard
practice among many physicians.
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Cell Carcinoma, click
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Latest Research on
Renal Cell Carcinoma
Genetika. 2008 Feb;44(2):250-6.
[Human chromosome 3P regions of putative tumor-suppressor genes
in renal, breast, and ovarian carcinomas]
[Article in Russian]
Loginov VI, Bazov IV, Khodyrev DS, Pronina IV, Kazubskaia TP, Ermilova VD,
Gar'kavtseva RF, Zbarovskiĭ ER, Braga EA.
Allelic imbalances (AI) of polymorphic markers at the short arm of chromosome 3
(3p) were mapped using DNA samples of renal cell carcinoma (RCC, 80 cases),
breast carcinoma (BC, 95 cases), and epithelial ovarian cancer (EOC, 50 cases)
at the same dense panel of markers (up to 24 loci). Six regions with the
increased AI frequency (versus the average values determined for all the
analyzed 3p markers) at RCC, BC or EOC were found in 3p chromosome. Four 3p
regions presumably contain suppressor genes of tumor growth (TSG) observed in
the epithelial tumors of various types. Region between D3S2409 and D3S3667
markers in the 3q21.31 region was identified in this study for the first time.
The AI peak in D3S2409-D3S3667 region was statistically significant (P < 0.001,
according to Fisher) when representative sample of 95 BC patients was analyzed.
The data on increased frequency of polymorphic marker allele amplification
suggest that the D3S2409-D3S3667 region contains both putative TSG and
protooncogenes.
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Lancet. 2008 Jul 12;372(9633):145-54. Epub 2008 Jul 3. Comment in: Lancet. 2008
Jul 12;372(9633):92-3.
An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen)
versus observation alone for patients at high risk of recurrence after
nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised
phase III trial.
Wood C, Srivastava P, Bukowski R, Lacombe L, Gorelov AI, Gorelov S, Mulders P,
Zielinski H, Hoos A, Teofilovici F, Isakov L, Flanigan R, Figlin R, Gupta R,
Escudier B; C-100-12 RCC Study Group.
M D Anderson Cancer Center, Houston, TX, USA. cgwood@mdanderson.org
BACKGROUND: Treatment of localised renal cell carcinoma consists of partial or
radical nephrectomy. A substantial proportion of patients are at risk for
recurrence because no effective adjuvant therapy exists. We investigated the use
of an autologous, tumour-derived heat-shock protein (glycoprotein 96)-peptide
complex (HSPPC-96; vitespen) as adjuvant treatment in patients at high risk of
recurrence after resection of locally advanced renal cell carcinoma. METHODS: In
this open-label trial, patients were randomly assigned to receive either
vitespen (n=409) or observation alone (n=409) after nephrectomy. Randomisation
was done in a one to one ratio by a computer-generated pseudo-random number
generator, with a block size of four, and was stratified by performance score,
lymph node status, and nuclear grade. Vitespen was given intradermally once a
week for 4 weeks, then every 2 weeks until vaccine depletion. The primary
endpoint was recurrence-free survival. The final analysis of recurrence-free
survival was planned to take place after 214 or more events of disease
recurrence or deaths before recurrence had occurred. Analysis was by intention
to treat (ITT). This study is registered with ClinicalTrials.gov, number
NCT00033904. FINDINGS: 48 patients in the vitespen group and 42 in the
observation group were excluded from the ITT population because they did not
meet post-surgery inclusion criteria; the ITT population thus consisted of 361
patients in the vitespen group and 367 in the observation group. Final analysis
of recurrence-free survival was triggered in November, 2005. Re-review of all
patients in the ITT population by the clinical events committee identified 149
actual recurrences (73 in the vitespen group and 76 in the observation group),
nine deaths before recurrence (two in the vitespen group and seven in the
observation group), and 124 patients with baseline metastatic or residual
disease (61 in the vitespen group and 63 in the observation group). Thus, after
a median follow-up of 1.9 years (IQR 0.9-2.5) in the ITT population, recurrence
events were reported in 136 (37.7%) patients in the vitespen group and 146
(39.8%) in the observation group (hazard ratio 0.923, 95% CI 0.729-1.169;
p=0.506). After continued follow-up until March, 2007, there had been 70 deaths
in the vitespen group and 72 in the observation group (p=0.896); however,
overall survival data were not mature, and patients continue to be followed up
for survival. In predefined exploratory analyses by AJCC stage, recurrence
events in patients with stage I or II disease were reported in 19 (15.2%)
patients in the vitespen group and 31 (27.0%) in the observation group (hazard
ratio 0.576, 95% CI 0.324-1.023; p=0.056). The most commonly reported adverse
events in the vitespen group were injection-site erythema (n=158) and
injection-site induration (n=153). One serious adverse event-autoimmune
thyroiditis of grade 2 severity-was reported in the vitespen group; no
treatment-related grade 3 or 4 adverse events were reported. INTERPRETATION: No
difference in recurrence-free survival was seen between patients given vitespen
and those who received no treatment after nephrectomy for renal cell carcinoma.
A possible improvement in recurrence-free survival in patients with early stage
disease who received vitespen will require further validation.
------
Urol Int. 2008;80(4):372-7. Epub 2008 Jun 27.
Activation of PI3K is associated with reduced survival in renal
cell carcinoma.
Merseburger AS, Hennenlotter J, Kuehs U, Simon P, Kruck S, Koch E, Stenzl
A, Kuczyk MA.
Department of Urology, Eberhard Karls University Tübingen, Tübingen, Germany.
OBJECTIVES: The epidermal growth factor receptor- (EGFR) activated
phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway is
associated with tumorigenesis and progression. The aims of the present study
were to determine the expression patterns of Akt pathway parameters PI3K,
phosphatase and tensin homolog (PTEN), phosphor-Akt (p-Akt) and their
combination, for their possible prognostic value in renal cell carcinoma (RCC).
PTEN dephosphorylates the liquid product of PI3K. METHODS: Tumor samples from
176 RCC patients were investigated for PTEN, p-Akt and PI3K expression by
immunohistochemistry. Expression levels were correlated to clinical variables
and postoperative outcome by uni- and multivariate statistical analysis.
RESULTS: The various expression levels within the tumor samples were independent
of histological grade and tumor stage, due to different levels of activation of
the PI3K/p-Akt pathway. The activation of PI3K protein was found to be
significantly associated with reduced survival times (p = 0.0304, multivariate
analysis). Analysis of combined biomarker expressions showed that decreased
long-term survival was correlated with PTEN low/p-Akt high expression (p <
0.05). CONCLUSIONS: Activation of the PI3K pathway is significantly associated
with adverse clinical outcome in RCC. Analysis of biomarker combinations might
identify high-risk patients and a subsequent need to adapt treatment modalities.
Molecular pathways regulating PI3K activation appear to be promising targets for
drug development in the clinical management of RCC patients. 2008 S. Karger AG,
Basel.
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Urol Int. 2008;80(4):367-71. Epub 2008 Jun 27.
Cytokine therapy response as a selection criterion for
cytoreductive nephrectomy in metastatic renal clear-cell carcinoma of
intermediate prognosis. Results and conclusions from a combined analysis.
Bex A, Haanen JB, Vyth-Dreese FA, Horenblas S, de Gast GC.
Department of Urology, The Netherlands Cancer Institute, Amsterdam, The
Netherlands. a.bex@nki.nl
AIMS: To assess the strategy of using an absence of progression at metastatic
sites following initial cytokine therapy outcome as a selection criterion for
nephrectomy in patients with synchronous metastatic renal carcinoma and an
intermediate prognosis according to the Memorial Sloan Kettering prognostic
index classification. MATERIALS AND METHODS: A combined retrospective analysis
of patients with clear-cell subtype from studies of initial cytokine treatment
response to assist with selection of patients for nephrectomy. We analyzed
survival times, UCLA integrated staging system scores, number of nephrectomies
and risk of progression to unresectability of the primary tumor during
treatment. RESULTS: There were 33 patients in total. Nephrectomies were not
performed in 10 (30%) patients whose cancers had progressed at metastatic sites.
Median survival time was 4 months with none of the patients dying of local tumor
progression. The median survival time of the 21 patients with nonprogressive
cancer and the primary removed was 17 months. Of those, 8 had a survival time <
or =1 year (median 8.5 months) and a progression-free survival time of 4 months
and 13 had a survival time >1 year (median 25 months). The median
progression-free survival time was 7 months (4-57 months). Four of the 5
objective responses at metastatic sites (5/33, 14%) occurred in those surviving
>1 year. CONCLUSIONS: We propose that progression at metastatic sites during
initial immunotherapy may be used to identify patients with a short survival
time and who are unlikely to benefit from nephrectomy. 2008 S. Karger AG, Basel.
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Praxis (Bern 1994). 2008 Apr 16;97(8):427-30.
[Current aspects in the therapy of renal cell cancer]
[Article in German]
Heynemann H.
Univ.-Klinik und Poliklinik für Urologie, Klinikum Medizinischen Fakultät,
Martin-Luther-Universität Halle-Wittenberg, Halle. hans.heynemann@medizin.uni-halle.de
The nephron-sparing partial nephrectomy has become the gold standard in the
surgical therapy of small renal tumors (4-7 cm). In metastased renal cell
cancers it is reasonable to perform a nephrectomy or a partial nephrectomy in
combination with cytokine-therapy (clear cell type) and/or a targeted therapy
with Angiogenesis-Inhibition, in presence of a Karnofsky-Index > 70%. A surgical
standard procedure for organ-confined renal cell cancers and an immunological
standard therapy for metastased renal cell cancers are no more proper; in fact
nowadays exists a spectrum of different efficient therapies. Surgery in
metastased diseases is indicated if it can improve the quality of life of the
patient.
------
Int J Cancer. 2008 Sep 1;123(5):1080-8.
Global analysis of metastasis-associated gene expression in
primary cultures from clinical specimens of clear-cell renal-cell carcinoma.
Tan X, Zhai Y, Chang W, Hou J, He S, Lin L, Yu Y, Xu D, Xiao J, Ma L,
Wang G, Cao T, Cao G.
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Metastatic clear-cell renal-cell carcinoma (ccRCC) has a poor prognosis and
unpredictable course, and there are no molecular markers that reliably predict
ccRCC metastasis. In this study, ccRCC specimens from 84 patients were directly
cultured in vitro. Primary cultures from 38 of 94 specimens contained more than
90% tumor cells at the fourth passage. After identification by immunostaining,
the primary cultures of metastatic and nonmetastatic ccRCC specimens from the
age- and gender-matched patients were subjected to cDNA microarray assays. A
total of 842 differentially expressed genes with a FDR (false discovery rate) of
4.79% were identified. Pathway analysis and co-occurrence with "cancer",
"metastasis" and "invasion" in the literature annotations functionally enriched
the 842 genes and provided an indication of the reliability of our microarray
assays. Novel genes associated with metastasis were selected based on
protein-protein interactions between 205 differentially expressed genes that
co-occurred with "metastasis" and those that did not co-occur with "metastasis"
on Medline, and the results of co-expression analysis between the co-occurred
genes and unpublished genes. FSTL1, AV722783, SLC15A1, DDX17, ORC2L and PKMYT1
were found to be potential ccRCC metastasis-associated novel genes, according to
expression patterns in cultures and tumor tissues. Interestingly, the
upregulated genes (CAV1, PKMYT1 and ORC2L) were also upregulated and the
downregulated genes (FSTL1, GSTM3, CYR61, SLC15A1 and AV722783) were also
downregulated in the primary ccRCC specimens compared with expression in
adjacent renal tissues in 37 patients. This study has identified new candidate
biomarkers and targets for the early diagnosis and treatment of ccRCC
metastasis.
------
Int J Cancer. 2008 Sep 1;123(5):1126-32.
A three-gene expression signature model to predict clinical
outcome of clear cell renal carcinoma.
Yao M, Huang Y, Shioi K, Hattori K, Murakami T, Sano F, Baba M, Kondo K,
Nakaigawa N, Kishida T, Nagashima Y, Yamada-Okabe H, Kubota Y.
Department of Urology and Molecular Genetics, Yokohama City University Graduate
School of Medicine, Yokohama, Japan. masayao@med.yokohama-cu.ac.jp
Renal cell carcinomas (RCCs) are morphologically and genetically heterogeneous
tumors and present diverse clinical courses. We developed a scoring system using
levels of gene expression to predict the outcome for clear cell RCC patients. We
selected differentially expressed genes from the DNA microarray data of 27 clear
cell RCCs; 16 were metastasis phenotypes and 11 were not. We compared the
selected gene set with previously published data and identified 33 overlapping
genes closely associated with patient outcome. We selected the 12 top-ranked
genes and confirmed the level of expression using quantitative reverse
transcriptase PCR. Multivariate Cox analysis revealed that 3 genes-vascular cell
adhesion molecule 1 (VCAM1), endothelin receptor type B (EDNRB), and regulator
of G-protein signaling 5 (RGS5)-were the most tightly associated with
cancer-specific survival and that higher expression of the 3 genes correlated
with better outcome. A formula for an outcome predictor was generated from
integration of the measurements of the expression levels of the 3 genes.
Multivariate Cox models combined with a split-sample cross-validation method in
a cohort of 386 clear cell RCC patients demonstrated that the derived score for
outcome prediction was an independent predictor in cancer-specific survival
tests. The accuracy of the prediction of cancer death after nephrectomy was
improved by the inclusion of this score in receiver operating characteristic
analysis from multivariate logistic regression models, suggesting that a scoring
system based on the expression levels of these 3 genes is useful in the
prediction of survival for patients with clear cell RCC.
------
Expert Rev Anticancer Ther. 2008 Jun;8(6):921-7.
Laparoscopic partial nephrectomy in the treatment of renal cell
carcinoma: a minimally invasive means to nephron preservation.
Blitstein J, Ghavamian R.
Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA.
jbliste@montefiore.org
With the advent of cross-sectional imaging, the incidence of asymptomatic
detected small renal masses, 'incidentalomas', has increased in the past 20
years. Recent studies have demonstrated that patients with renal masses have
worse renal function at baseline and have more comorbidities than the general
population. Nephron-sparing surgery allows for maximal preservation of
functioning nephrons with comparable oncologic outcomes. Recently, laparoscopic
partial nephrectomy has emerged as a minimally invasive nephron-sparing surgical
option for treating the appropriately selected renal mass. While open-partial
nephrectomy has undisputedly become standard of care for the management of the
small renal mass (<4 cm), laparoscopic partial nephrectomy is becoming the
preferred option for select patients in institutions in which advanced
laparoscopic experience is available.
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Expert Rev Anticancer Ther. 2008 Jun;8(6):907-19.
Immunotherapy for renal cell cancer in the era of targeted
therapy.
Coppin C.
Medical Oncology, University of British Columbia & BC Cancer Agency, Vancouver,
Canada. ccoppin@bccancer.bc.ca
Until recently, cytokine therapy has been the only validated option for patients
with advanced renal cancer. IFN-alpha is one of very few treatments that have
demonstrated improved median survival compared with the appropriate control. In
patients with synchronous metastases at diagnosis, debulking nephrectomy prior
to interferon, further improves overall survival. High-dose IL-2 appears to be
able to cure a small percentage of highly selected patients. There is potential
to further improve patient selection for these options. The demonstrated value
of cytokines should not be overlooked in the rush to use new drugs. In the
adjuvant setting, vaccine therapy has provided the only systemic approach that
has any promise. New insights into the complexities of the immune system at the
molecular level, as well as the ingenuity and enthusiasm of immunotherapists,
will undoubtedly lead to continuing attempts to identify and overcome obstacles
to achieve the grail of human tumor rejection in clinical practice. Targets
within the immune regulatory system and the use of vaccines as targeting agents
may bring together the fields of immunotherapy and targeted therapy in the near
future.
------
Expert Rev Anticancer Ther. 2008 Jun;8(6):895-905.
Molecular genetics of hereditary renal cancer: new genes and
diagnostic and therapeutic opportunities.
Hansel DE, Rini BI.
Department of Anatomic Pathology, Glickman Urological & Kidney Institute and
Taussig Cancer Institute, The Cleveland Clinic, 9500 Euclid Avenue, Desk L25,
Cleveland, OH 44195, USA. hanseld@ccf.org
Renal cell carcinoma may be sporadic or occur in the setting of an inherited
cancer syndrome, such as von Hippel-Lindau or Birt-Hogg-Dube syndrome. Although
the clinical spectrum of heritable renal cancer syndromes varies significantly,
commonalities include the often young age of presentation, multifocal and
bilateral nature of renal lesions, and autosomal dominant pattern of
inheritance. Molecular studies have recently begun to elucidate the genetic
abnormalities and subsequent alterations in downstream intracellular signaling
cascades that underlie the development of these syndromes. This review will
highlight the clinicopathologic and molecular features associated with the
diverse array of heritable renal cancer syndromes and emphasize the potential
cellular pathways that may be utilized to develop novel treatment strategies for
patients with these syndromes.
------
Expert Rev Anticancer Ther. 2008 Jun;8(6):887-93.
Chemokines as therapeutic targets in renal cell carcinoma.
Reckamp KL, Strieter RM, Figlin RA.
Divisions of Medical Oncology and Therapeutics Research & Hematology, City of
Hope and Beckman Research Institute, 1500 E Duarte Road, MOB 1001, Duarte, CA
91010, USA. kreckamp@coh.org
Targeting novel pathways associated with tumor angiogenesis, invasion and
immunity, may lead to improvement in patient outcomes for renal cell carcinoma.
Chemokines potentiate tumor growth, metastasis, angiogenesis and immune evasion
through interactions with stromal cells and neoplastic cells. Further
understanding of the mechanisms involved in chemokine-mediated angiogenesis and
metastasis may lead to improved therapeutic strategies in this disease.
Interactions between chemokine expression and signaling, and the VEGF and
hypoxia-inducible factor pathways offer important opportunities to intervene in
the process of renal cell carcinoma proliferation, angiogenesis and invasion.
Modulation of the CXCR3/CXCR3-ligand or the CXCR4/CXCL12 biologic axis may be
potential therapeutic targets for the treatment of renal cell carcinoma.
Furthermore, combination treatment with agents targeting chemokine signaling
with therapies directed at angiogenesis and tumor immunity may lead to improved
outcomes in this disease.
------
Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006017.
Targeted therapy for advanced renal cell carcinoma.
Coppin C, Le L, Porzsolt F, Wilt T.
BACKGROUND: Advanced renal cell carcinoma has been resistant to drug therapy of
different types and new types of drug therapy are needed. Targeted agents
inhibit known molecular pathways involved in cellular proliferation and
neoangiogenesis, the induction by the tumour of host microvascular networks.
Angiogenesis is of special interest in the clear cell histologic subtype of
renal cancer because of its vascularity and constitutively activated
hypoxia-inducible path in the majority of tumours. OBJECTIVES: 1) To provide a
systematic review of studies testing targeted agents.2) To identify the type and
degree of clinical benefit, if any, of targeted agents over the prior standard
of care, particularly any impact on overall survival. SEARCH STRATEGY: 1)
Electronic search of CENTRAL, MEDLINE and EMBASE databases.2) Hand search of
international cancer meeting abstract and other sources specified in the
protocol. SELECTION CRITERIA: Randomized controlled studies of targeted agents
in patients with advanced renal cell cancer reporting major remission rate or
overall survival by allocation. Progression-free survival (PFS) was adopted as
an additional outcome because PFS was a commonly chosen primary outcome, and
because several pivotal studies allowed crossover from the control to the
investigational arm after closure to accrual thereby making overall survival a
problematic endpoint. DATA COLLECTION AND ANALYSIS: Nineteen fully eligible
studies tested ten different targeted agents (Table 04). One additional study
was excluded because no outcome data by allocation have been reported (Hutson
2007). For purposes of comparison, the studies were divided into three groups:
Group 1 studies compared different doses of the same agents; Group 2 studies
examined the impact of targeted agents in patients who had received prior
cytokine or other systemic therapy; and Group 3 studies tested targeted agents
in systemically naive patients, either against standard inter
feron-alfa or against another control therapy. Meta-analysis was not utilized
because there were very few situations where the same agents had been tested in
the same group in more than one study. MAIN RESULTS: In systemically untreated
patients in studies using subcutaneous interferon-alfa as control therapy, the
major findings were: 1) An improvement in overall survival has been demonstrated
only with the use of weekly intravenous temsirolimus in patients with unselected
renal cancer histology and adverse prognostic features (median survival 10.9
months versus 7.3 months for temsirolimus or interferon-alfa respectively, HR
0.73, P = 0.008 log rank, Hudes 2007). However, the chance of major remission
was low and not improved with temsirolimus. 2) In patients with mostly good or
intermediate prognostic risk with clear cell renal cancer, oral sunitinib
improves the chance of major remission, the probability of symptomatic
improvement, and freedom from disease progression (Motzer 2007); in a similar
setting, the addition of biweekly intravenous bevacizumab to interferon-alfa
also improved the chance of major remission and prolonged progression-free
survival (Escudier 2007b); overall survival had not changed at the time of
interim reporting of either study.In patients with clear cell renal cancers who
had failed prior cytokine therapy, oral sorafenib gives a better quality of life
than placebo as well as improved chance of being free of disease progression;
overall survival may have improved but is hard to evaluate because of crossover
of placebo-assigned patients after the study closed to accrual (Escudier 2007a).
AUTHORS' CONCLUSIONS: Based on less than a decade of experience, some targeted
agents with specified molecular targets have demonstrated clinically useful
benefits over the previous standard of care for patients with advanced renal
cancer. Much more research is required to fully establish the role of targeted
agents in this condition.
-----
Br J Cancer. 2008 Apr 22;98(8):1336-41. Epub 2008 Mar 25.
Vaccination of metastatic renal cell carcinoma patients with
autologous tumour-derived vitespen vaccine: clinical findings.
Jonasch E, Wood C, Tamboli P, Pagliaro LC, Tu SM, Kim J, Srivastava P, Perez C,
Isakov L, Tannir N.
1Department of Genitourinary Medical Oncology, University of Texas MD Anderson
Cancer Center, 1515 Holcombe Boulevard, Unit 1374, Houston, Texas 77030, USA.
The aim of this study was to evaluate the clinical efficacy as determined by
time to progression and response rate (RR) of autologous vitespen (formerly
HSPPC-96; Oncophage, Antigenics Inc., New York, NY, USA) with and without
interleukin-2 (IL-2; Proleukin: Chiron, Emoryville, CA, USA) in stage IV
metastatic renal cell carcinoma (RCC) patients undergoing nephrectomy.
Eighty-four patients were enrolled on study, and then underwent nephrectomy and
harvest of tumour tissue for use in autologous vaccine manufacture. Initial
treatment schedule started approximately 4 weeks after surgery and consisted of
six injections: once weekly for 4 weeks, then two injections biweekly (vaccines
administered at weeks 1, 2, 3, 4, 6, 8), followed by restaging at or around week
10. Patients who had stable or responsive disease continued to receive vaccine,
with four more vaccinations biweekly (at weeks 10, 12, 14, 16). Patients who had
progressive disease at week-10 evaluation received four consecutive
5-day-per-week courses of 11 x 10(6) U of IL-2 subcutaneously (weeks 10, 11, 12,
13), with four doses of vitespen at 2-week intervals (at weeks 10, 12, 14, 16).
At the next evaluation (week 18), patients with a complete response received two
further cycles of vitespen (with IL-2 if also received during prior cycle) or
until vaccine supply was exhausted. Patients with stable disease or partial
response repeated their prior cycle of therapy. Disease progressors who had not
yet received IL-2 began IL-2 treatment, and progressors who had already received
IL-2 came off study. Of 60 evaluable patients, 2 demonstrated complete response
(CR), 2 showed partial response (PR), 7 showed stable disease, and 33 patients
progressed. Sixteen patients had unconfirmed stable disease. Two patients who
progressed on vaccine alone experienced disease stabilisation when IL-2 was
added. Treatment with vitespen did not result in a discernable benefit in the
majority of patients with metastatic RCC treated in this study. Use in
combination with immunoregulatory agents may enhance the efficacy of
vitespen.British Journal of Cancer (2008) 98, 1336-1341.
doi:10.1038/sj.bjc.6604266 www.bjcancer.com Published online 25 March 2008.
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J Clin Oncol. 2008 Apr 20;26(12):2034-9. Epub 2008 Mar 17.
Phase I study of recombinant interleukin-21 in patients with
metastatic melanoma and renal cell carcinoma.
Thompson JA, Curti BD, Redman BG, Bhatia S, Weber JS, Agarwala SS, Sievers EL,
Hughes SD, DeVries TA, Hausman DF.
Seattle Cancer Care Alliance, 825 Eastlake Ave East, Mailstop G4-830, Seattle,
WA 98109-1023, USA. jat@u.washington.edu
PURPOSE: A phase I study of patients with metastatic malignant melanoma (MM) and
renal cell carcinoma (RCC) evaluated the safety and maximum tolerated dose (MTD),
pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of
recombinant human interleukin-21 (rIL-21). PATIENTS AND METHODS: Patients who
had one or fewer prior systemic treatments for metastatic MM or RCC were treated
with rIL-21 administered for two 5-day cycles on days 1 through 5 and 15 through
19 of a treatment course; rIL-21 was administered by rapid intravenous infusion
in an outpatient setting. Cohorts of patients received doses ranging from 3 to
100 microg/kg/dose, and an expanded cohort was treated at the MTD. Patients with
stable disease (SD) or better could receive additional treatment cycles.
RESULTS: Forty-three patients were treated (24 MM; 19 RCC), including 28 in the
expanded cohort. Dose-limiting toxicities consisted primarily of transient grade
3 laboratory abnormalities. The MTD was estimated to be 30 microg/kg. The most
common adverse events included flu-like symptoms, pruritus, and rash. Twelve
patients received up to five additional two-cycle courses of treatment without
cumulative toxicity, except for one patient with reversible grade 4
hepatotoxicity. Serum concentrations of rIL-21 increased in a dose-proportional
manner. Dose-dependent increases in soluble CD25 reflected lymphocyte
activation. Antitumor activity was observed in both MM (one complete response
and 11 SD) and RCC (four partial responses, 13 SD). CONCLUSION: Outpatient
therapy with rIL-21 at 30 microg/kg was well tolerated, had dose-dependent
pharmacokinetics and pharmacodynamics, and was associated with antitumor
activity in patients with MM and RCC.
-----
J Urol. 2008 Apr 16 [Epub ahead of print]
Waiting Time From Initial Urological Consultation to Nephrectomy
for Renal Cell Carcinoma-Does it Affect Survival?
Stec AA, Coons BJ, Chang SS, Cookson MS, Herrell SD, Smith JA Jr, Clark PE.
Department of Urology, Vanderbilt University Medical Center, Nashville,
Tennessee.
PURPOSE: We report survival and recurrence outcomes in all patients undergoing
radical or partial nephrectomy for renal cell carcinoma, as related to surgical
waiting time. MATERIALS AND METHODS: We retrospectively reviewed the records of
722 patients who underwent surgical resection for renal cell carcinoma. Patients
were subdivided by waiting time from the initial urology visit until surgery.
Surgical waiting time was evaluated as a continuous variable and by monthly
subgroups. Univariate and multivariate analyses were performed to evaluate
factors associated with overall, disease specific and recurrence-free survival.
RESULTS: Mean time from the first visit to surgery was 1.2 months with 64.1% and
94.3% of patients undergoing surgery within 30 days and within 3 months,
respectively. Overall and disease specific survival was not affected by surgical
waiting time regardless of how time was analyzed. On univariate analysis 5-year
recurrence-free survival was poorer in patient
s undergoing surgery within 1 month vs more than 1 month (75.7% vs 88.4%, p =
0.02). On multivariate analysis T stage (p <0.0001), grade (p = 0.009), lymph
node involvement (p = 0.0001) and histology (p = 0.006) were independent
predictors of recurrence-free survival, while surgical waiting time was not (p =
0.18). Surgical waiting time less than 1 month was associated with higher stage
and higher grade tumors (p <0.0001 and 0.0006, respectively). CONCLUSIONS:
Surgical waiting time from initial urological consultation to operative
intervention does not adversely affect the outcome of renal cell carcinoma
within the time frames analyzed in this study, in which 94% of cases occurred
within 3 months. Individual urologist judgment remains a critical factor in the
appropriate and timely care of the patient with a suspicious renal mass.
-----
J Urol. 2008 Apr 16 [Epub ahead of print]
Percutaneous Renal Cryoablation: Experience Treating 115 Tumors.
Atwell TD, Farrell MA, Leibovich BC, Callstrom MR, Chow GK, Blute ML, Charboneau
JW.
Department of Radiology (TDA, MAF, MRC, JWC), Mayo Clinic, Rochester, Minnesota.
PURPOSE: We determined technical feasibility, safety and short-term outcomes
following percutaneous renal cryoablation. MATERIALS AND METHODS: We performed a
retrospective review of 115 renal tumors in 110 patients treated with
percutaneous cryoablation. Specific attention was directed to tumor
characteristics, hospital course, complications, technical success and treatment
success based on followup imaging. RESULTS: Mean tumor size was 3.3 cm (range
1.5 to 7.3), including 29 tumors 4.0 cm or larger and 21 tumors in the anterior
kidney. Of 90 renal mass biopsies performed 52 (58%) showed renal cell
carcinoma. All patients were admitted to the hospital following cryoablation and
most (87%) were discharged home the next day (range 1 to 12 days). There were 7
major complications associated with the 113 cryoablation procedures (6%).
Technical success was achieved in 112 of the 115 (97%) treated tumors and 3
residual tumors were seen on 3 month followup imaging. In 80 tumors followed 3
months or longer (mean 13.3 months) There has been no local progression of (100%
treatment success). CONCLUSIONS: Percutaneous renal cryoablation is technically
feasible and relatively safe. With experience many anterior tumors and tumors
larger than 4 cm can be successfully treated. Long-term followup remains
necessary to prove treatment durability.
-----
Oncology. 2008 Apr 16;73(3-4):204-209 [Epub ahead of print]
Safety and Activity of Sorafenib in Different Histotypes of
Advanced Renal Cell Carcinoma.
Procopio G, Verzoni E, Gevorgyan A, Mancin M, Pusceddu S, Catena L, Platania M,
Guadalupi V, Martinetti A, Bajetta E.
Medical Oncology Unit 2, Fondazione IRCCS ‘Istituto Nazionale dei Tumori’,
Milano, Italy.
Background: The aim of our study was to evaluate the efficacy and safety in
unresectable or advanced renal carcinoma treated with sorafenib, in a situation
closely similar to the everyday medical practice. Patients and Methods: One
hundred and thirty-six patients have been treated with 400 mg b.i.d. of
sorafenib administered orally until disease progression or unacceptable
toxicity. They were either previously untreated or relapsed after one or more
previous treatments with systemic therapy. Most of them had clear cell renal
carcinoma (RCC), but other histological types such as papillary, chromophobe,
Bellini ducts, sarcomatoid and mixed forms were also represented. Results:
Overall disease control of 70.6% was achieved with 7.9% of partial remissions.
Response was observed in the majority of patients with RCC, but also in some
patients with non-clear cell RCC. Safety was acceptable, with the most common
adverse events consisting of hand-foot skin reaction, cutaneous rash, diarrhoea,
fatigue and hypertension. Conclusions: The results confirm previous ones
reported in the literature concerning the efficacy and the safety of sorafenib
as second-line treatment in patients with RCC. In addition, they disclose the
hypothesis that sorafenib could be effective also in patients who underwent
multiple previous treatments and in those with histology different from clear
cells. Copyright (c) 2008 S. Karger AG, Basel.
-----
BJU Int. 2008 Apr 10 [Epub ahead of print]
Renal tumour surgery in elderly patients.
Roos FC, Pahernik S, Melchior SW, Thüroff JW.
Department of Urology, Johannes Gutenberg-University, Medical School, Mainz,
Germany.
OBJECTIVE To analyse morbidity, renal function and oncological outcome in
patients aged >/=80 years who had surgery for renal tumours, as in the elderly
such surgery is controversial in relation to life-expectancy and other causes of
death. PATIENTS AND METHODS Between 1990 and 2006, in our institution 1625
patients had surgery to treat solid renal tumours suspected to be renal cell
carcinoma (RCC); 62 (4%) were aged >/=80 years (mean 82.5), and 73% of these
elderly patients had radical nephrectomy (RN) and 27% nephron-sparing surgery (NSS).
Results The median (range) follow-up was 3.1 (0.2-14.1) years (89% of the
patients). There was no perioperative mortality. There were only minor
complications in 47% of patients, most (34%) being temporary increases in serum
creatinine level. Histopathologically, 10% of the 62 patients had benign lesions
and 90% had RCC. Of the 56 patients with RCC, the stage was pT1a in 34%, pT1b in
25%, pT2 in 5% and pT3 in 36%. For those treated with RN the median (range)
serum creatinine level before and after RN was 1.0 (0.7-1.8) and 1.4 (1.0-2.8)
mg/dL (P < 0.05), and for those treated with NSS were 1.1 (0.7-4.4) and 1.2
(0.7-4.8) mg/dL (not significant), respectively. The 5-year overall survival was
68% and the cancer-specific survival was 85%. CONCLUSIONS Surgery for renal
tumours is safe in elderly patients, with a low perioperative morbidity and a
good overall survival rate. Patients should be selected carefully according to
comorbidities, biological age and social support.
-----
BJU Int. 2008 Apr 2 [Epub ahead of print]
Enucleation of renal cell carcinoma with ablation of the tumour
base.
Kutikov A, Vanarsdalen KN, Gershman B, Fossett LK, Guzzo TJ, Wein AJ, Malkowicz
SB.
Division of Urology, Department of Surgery, Hospital of the University of
Pennsylvania, Philadelphia, PA, USA.
OBJECTIVE To retrospectively assess the effectiveness of cancer control with
enucleation of renal cell carcinoma (RCC), which is surgically expedient, allows
preservation of maximal renal parenchyma, and makes intraoperative renal
ischaemia unnecessary, by two surgeons routinely enucleating renal tumours and
ablating the tumour bed with argon beam and the Nd-YAG laser. PATIENTS AND
METHODS Between 1996 and 2006 at our institution, 97 patients had RCC
enucleated, with ablation of the tumour base. Patients with lesions other than
RCC and those with von Hippel-Lindau disease or Birt-Hogg-Dube syndrome were
excluded from the study. The mean follow-up was 24.9 months. Patients were
evaluated for RCC recurrence with cross-sectional imaging at least every 6
months for the first 2 years and then annually thereafter. RESULTS The mean
(median, range) tumour size was 2.8 (2.5, 0.8-7.0) cm. Of the 97 patients only
one had disease progression after a mean follow-up of 24.9 months. This pa
tient presented with a solitary grade 2 clear cell RCC and had a local
recurrence 30 months after original surgery. CONCLUSIONS The present series and
other available clinical data suggest that enucleation with cavity ablation is
an oncologically sound approach that is simple, versatile and obviates the need
for renal ischaemia.
-----
Expert Rev Anticancer Ther. 2008 Mar;8(3):481-90.
Improving outcomes in patients with advanced renal cell
carcinoma.
Sosman JA.
Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN
37232, USA. jeff.sosman@vanderbilt.edu
The emergence of targeted therapies for advanced renal cell carcinoma has been a
dramatic turning point in improving outcomes for the majority of patients with
this disease. In study populations comprising primarily good- and
intermediate-risk patients with clear cell renal cell carcinoma and prior
nephrectomy, prolonged progression-free survival was demonstrated for three
angiogenesis-targeted agents: sunitinib (compared with interferon [IFN]),
bevacizumab plus IFN (vs IFN alone) and sorafenib (vs placebo in
cytokine-refractory patients). As a first-line treatment for patients with
multiple poor-risk factors, temsirolimus, which inhibits mTOR, has improved not
only progression-free survival compared with IFN but, more importantly, overall
survival. Further studies are needed to determine whether combinations and/or
sequencing of these targeted agents can further improve outcomes.
-----
Urol Oncol. 2008 Jan-Feb;26(1):102.
Intermediate comparison of partial nephrectomy and radiofrequency ablation for
clinical T1a renal tumors.
Stern JM, Svatek R, Park S, Hermann M, Lotan Y, Sagalowsky AI, Cadeddu JA,
Department of Urology, University of Texas, Southwestern Medical Center, Dallas,
TX.Boorjian SA, Blute ML.
OBJECTIVE: To compare the intermediate term outcomes of patients with clinical
T1a renal tumors who were treated with nephron-sparing surgery by partial
nephrectomy (PN), the preferred approach for small (cT1a) renal tumors, or
radiofrequency ablation (RFA), recently offered to selected patients as an
alternative, less morbid technique. PATIENTS AND METHODS: We identified patients
with stage T1a renal masses who had >/=2 years of follow-up; those with
bilateral synchronous or metachronous tumors, metastatic disease at
presentation, or a family history of renal cell carcinoma were excluded. From
July 1996 to January 2004, 110 PNs were identified in our database; 37 patients
who fulfilled the inclusion criteria had either open (30) or laparoscopic PN
(7), and 40 had either percutaneous (26) or laparoscopic (14) RFA. RESULTS: The
mean (range) follow-up for the RFA and PN groups was 30 (18-42) and 47 (24-93)
months, respectively; the respective mean tumor size was 2.41 and 2.43 c
m. There was 1 incomplete ablation and 2 local recurrences in the RFA group, and
2 recurrences in the PN group (1 local and 1 in the contralateral kidney). There
were no disease-specific deaths. The overall actuarial disease-free probability
for the PN and RFA groups, respectively, was 95.8% and 93.4% (P = 0.67).
CONCLUSIONS: This initial 3-year actuarial analysis showed that RFA for cT1a
renal tumors has comparable oncological outcomes to PN; however, longer term
data are still needed.
-----
Urol Oncol. 2008 Jan-Feb;26(1):102-3.
Renal cell carcinoma clinically involving adjacent organs: Experience with
aggressive surgical management.
Margulis V, Sánchez-Ortiz RF, Tamboli P, Cohen DD, Swanson DA, Wood CG,
Department of Urology, University of Texas, M.D. Anderson Cancer Center,
Houston, TX.Russo P.
BACKGROUND: Historically, patients with nonmetastatic renal cell carcinoma (RCC)
involving adjacent organs have been considered inoperable and incurable. The
oncologic efficacy of an aggressive surgical approach was evaluated in a
selected subpopulation of RCC patients. Further, an attempt was made to define
the clinical and pathologic characteristics predictive of surgical failure.
METHODS: With Institutional Review Board approval, the institutional nephrectomy
database of 3,470 patients treated at M. D. Anderson Cancer Center from 1990 to
2006 was searched for RCC patients treated with radical nephrectomy and
resection of at least 1 adjacent organ thought to be directly involved by RCC.
Patients with nonmetastatic RCC and a minimum follow-up of 6 months were
included in the analysis. RESULTS: In all, 30 patients with clinical T4NxM0 RCC
and median follow-up of 32.3 months (range, 8.5-140.1) met the study inclusion
criteria and comprise the dataset for the analysis. On pathologic evaluation 60% of patients were clinically overstaged, as only 12 (40%) of
30 patients demonstrated direct invasion into adjacent organs resected. None of
the clinical tumor characteristics predicted a finding of pathologic T4 RCC.
Nodal involvement and pathologic T stage were significant independent predictors
of disease recurrence (hazard ratio [HR] 3.726, P = 0.043, and HR 2.414, P =
0.045, respectively) and cancer-specific survival (HR 17.145, P = 0.002, and HR
3.791, P = 0.024, respectively). Disease recurred in 11 of 18 (61.1%) of <pT4
patients and in 10 of 12 (83.3%) of pT4 patients at a median 13.3 and 2.3
months, respectively; 13 (73.3%) <pT4 patients and 5 (41.7%) pT4 patients were
alive at the time of analysis. CONCLUSIONS: True pathologic involvement of
adjacent organs by RCC cannot be predicted from pre- or intraoperative
parameters. A significant proportion of patients clinically suspected of having
T4 RCC are downstaged, and benefit from aggressive surgical resection with en bloc removal of involved organs.
-----
Urol Oncol. 2008 Jan-Feb;26(1):101-2.
A prospective randomized EORTC intergroup Phase 3 study comparing the
complications of elective nephron-sparing surgery and radical nephrectomy for
low-stage renal cell carcinoma.
Van Poppel H, Da Pozzo L, Albrecht W, Matveev V, Bono A, Borkowski A, Marechal
JM, Klotz L, Skinner E, Keane T, Claessens I, Sylvester R, European Organization
for Research and Treatment of Cancer (EORTC); National Cancer Institute of
Canada Clinical Trials Group (NCIC CTG); Southwest Oncology Group (SWOG);
Eastern Cooperative Oncology Group (ECOG). Department of Urology, University
Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium.Boorjian
SA, Blute ML.
OBJECTIVES: This study compared the complications and the cancer control of
elective nephron-sparing surgery (NSS) and radical nephrectomy (RN) in patients
with a small (</=5 cm), solitary, low-stage N0 M0 tumor suspicious for renal
cell carcinoma (RCC), and a normal contralateral kidney. METHODS: Five hundred
forty-one patients were randomized in a prospective, multicenter, Phase 3 trial
to undergo NSS (n = 268) or RN (n = 273) together with a limited lymph node
dissection. RESULTS: This publication reports only on the complications reported
for both surgical methods. The rate of perioperative blood loss was slightly
higher after RN (96.0% vs. 87.2%) and the rate of severe hemorrhage was slightly
higher after NSS (3.1% vs. 1.2%). Ten patients (4.4%), all of whom were treated
with NSS, developed urinary fistulas. Pleural damage (11.5% for NSS vs. 9.3% for
RN) and spleen damage (0.4% for NSS and 0.4% for RN) were observed with similar
rates in both groups. Postoperative computed tomography scanning abnormalities were seen in 5.8% of NSS and 2.0% of RN
patients. Reoperation for complications was necessary in 4.4% of NSS and 2.4% of
RN patients. CONCLUSIONS: NSS for small, easily resectable, incidentally
discovered RCC in the presence of a normal contralateral kidney can be performed
safely with slightly higher complication rates than after RN. The oncologic
results are eagerly awaited to confirm that NSS is an acceptable approach for
small asymptomatic RCC.
-----
J Clin Oncol. 2008 Jan 1;26(1):127-31.
Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe
renal cell carcinoma.
Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, Zhou M, Rini
BI, Bukowski RM, Escudier B.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Toni_Choueiri@dfci.harvard.edu
PURPOSE: Sunitinib and sorafenib are novel tyrosine kinase inhibitors (TKIs)
that have shown significant clinical activity in metastatic clear cell renal
cell carcinoma (RCC). The activity of sunitinib and sorafenib in non-clear cell
histologies has not been evaluated. PATIENTS AND METHODS: Clinical features at
study entry and treatment outcomes were evaluated in patients with metastatic
papillary RCC (PRCC) and chromophobe RCC (ChRCC) who received either sunitinib
or sorafenib as their initial TKI treatment in five US and French institutions.
Response rate and survival were documented. Fisher's exact test was used for
categoric variables, and the Kaplan-Meier method was used to estimate survival.
RESULTS: Fifty-three patients were included. The number of patients with
papillary and chromophobe histologies was 41 (77%) and 12 (23%), respectively.
Response rate, progression-free survival (PFS) time, and overall survival time
for the entire cohort were 10%, 8.6 months, and 19.6
months, respectively. Three (25%) of 12 ChRCC patients achieved a response (two
patients treated with sorafenib and one treated with sunitinib), and PFS was
10.6 months. Two (4.8%) of 41 PRCC patients achieved a response (both patients
were treated with sunitinib). PFS for the whole cohort was 7.6 months. Sunitinib-treated
PRCC patients had a PFS of 11.9 months compared with 5.1 months for sorafenib-treated
patients (P < .001). CONCLUSION: Patients with PRCC and ChRCC may have prolonged
PFS from sunitinib and sorafenib, although clinical responses remain overall low
in PRCC. Additional prospective trials with these agents in non-clear cell RCC
will further clarify their use in the future.
-----
Lancet. 2007 Dec 22;370(9605):2103-11.
Comment in:
Lancet. 2007 Dec 22;370(9605):2071-3.
Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell
carcinoma: a randomised, double-blind phase III trial.
Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C,
Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I,
Jagiello-Gruszfeld A, Moore N; AVOREN Trial investigators.
Department of Medicine, Institut Gustave Roussy, Villejuif, France. escudier@igr.fr
BACKGROUND: Vascular endothelial growth factor (VEGF) inhibition is a valid
therapeutic approach in renal cell carcinoma. Therefore, an investigation of the
combination treatment of the humanised anti-VEGF monoclonal antibody bevacizumab
with interferon alfa was warranted. METHODS: In a multicentre, randomised,
double-blind, phase III trial, 649 patients with previously untreated metastatic
renal cell carcinoma were randomised to receive interferon alfa-2a (9 MIU
subcutaneously three times weekly) and bevacizumab (10 mg/kg every 2 weeks;
n=327) or placebo and interferon alfa-2a (n=322). The primary endpoint was
overall survival. Secondary endpoints included progression-free survival and
safety. An interim analysis of overall survival was prespecified after 250
deaths. On the basis of new second-line therapies that became available while
the trial was in progress, which could have confounded analyses of overall
survival data, we agreed with regulatory agencies that the pre-planned final analysis of progression-free survival would be acceptable for
regulatory submission. The protocol was amended to allow the study to be
unblinded at this point. The final analysis of progression-free survival is
reported here. Efficacy analyses were done by intention to treat. This trial is
registered with centerwatch.com, number BO17705E. FINDINGS: 325 patients in the
bevacizumab plus interferon alfa group and 316 in the placebo plus interferon
alfa group received at least one dose of study treatment. At the time of
unblinding, 230 progression events had occurred in the bevacizumab plus
interferon alfa group and 275 in the control group; there were 114 deaths in the
bevacizumab plus interferon alfa group and 137 in the control group. Median
duration of progression-free survival was significantly longer in the
bevacizumab plus interferon alfa group than it was in the control group (10.2
months vs 5.4 months; HR 0.63, 95% CI 0.52-0.75; p=0.0001). Increases in progression-free survival were seen with bevacizumab plus interferon alfa irrespective
of risk group or whether reduced-dose interferon alfa was received. Deaths due
to adverse events were reported in eight (2%) patients who received one or more
doses of bevacizumab and seven (2%) of those who did not receive the drug. Only
three deaths in the bevacizumab arm were considered by investigators to be
possibly related to bevacizumab. The most commonly reported grade 3 or worse
adverse events were fatigue (40 [12%] patients in the bevacizumab group vs 25
[8%] in the control group) and asthenia (34 [10%] vs 20 [7%]). INTERPRETATION:
The combination of bevacizumab with interferon alfa as first-line treatment in
patients with metastatic renal cell carcinoma results in a significant
improvement in progression-free survival, compared with interferon alfa alone.
-----
Expert Rev Anticancer Ther. 2007 Dec;7(12):1749-61.
Current status of cytoreductive nephrectomy in metastatic renal cell carcinoma.
Harshman LC, Srinivas S.
Fellow, Medical Oncology, Stanford University School of Medicine, Division of
Medical Oncology, 875 Blake Wilbur Drive, Stanford, CA 94305, USA.
laurenhs@stanford.edu
The incidence of metastatic renal cell carcinoma (mRCC) continues to rise. While
treatment options have increased dramatically in the last few years, few
patients achieve a cure. The standard of care for mRCC in cytokine-eligible
candidates is nephrectomy followed by high-dose IL-2. High-dose IL-2 can induce
durable complete remissions, but only select patients can enjoy its benefits
owing to toxicities. While not curative, the newer targeted therapies offer a
broader patient population the chance for treatment response and prolonged
survival. This review highlights the historical background of cytoreductive
nephrectomy in mRCC, discusses the available treatment options and considers
alternative treatment paradigms, such as the integration of the targeted agents
with nephrectomy and the use of systemic therapy as medical selection for
determining appropriate nephrectomy candidates.
-----
Urology. 2007 Nov;70(5):900-4; discussion 904.
Surgical resection provides excellent outcomes for patients with cystic clear
cell renal cell carcinoma.
Webster WS, Thompson RH, Cheville JC, Lohse CM, Blute ML, Leibovich BC.
Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA.
OBJECTIVES: Previous observations suggest that cystic clear cell renal cell
carcinoma (RCC) is cured with surgical resection. However, long-term outcome
data are lacking. We reviewed our experience with RCC and report on pathologic
features and patient outcome associated with the cystic variant. METHODS: We
identified 2431 patients treated with nephrectomy for unilateral, sporadic clear
cell RCC between 1970 and 2002. A single urologic pathologist (J.C.C.) reviewed
all of the microscopic slides without knowledge of patient outcome. Cystic clear
cell RCC was characterized by numerous confluent cysts lined by clear cells, and
containing nests of clear cells within the cyst walls. RESULTS: There were 85
(3.5%) patients with cystic RCC. Among these patients, 22 died during follow-up,
although no patient died of RCC. The median follow-up for the remaining 63
patients was 5 years. The estimated cancer-specific survival rate at 5 years
after surgery for patients with noncystic clear
cell RCC was 70.6% compared with 100% for patients with the cystic variant (P
<0.001). This difference persisted even when comparing patients with cystic RCC
to the subset with noncystic RCC who had pT1, pNx/pN0, and no clinical evidence
of metastases (cM0). No patient with cystic clear cell RCC had extrarenal
disease at time of nephrectomy with the exception of 1 patient who had
perinephric fat invasion. CONCLUSIONS: Cystic RCC is a distinct pathologic
entity and should be assessed routinely during pathologic evaluation.
Furthermore, we present data supporting that cystic RCC patients should expect
to be cured after surgical extirpation.
-----
Eur Urol. 2007 Nov 20 [Epub ahead of print]
Nephron-Sparing Surgery versus Radical Nephrectomy in the Treatment of
Intracapsular Renal Cell Carcinoma up to 7cm.
Antonelli A, Cozzoli A, Nicolai M, Zani D, Zanotelli T, Perucchini L, Cunico SC,
Simeone C.
Department of Urology, University of Brescia, Brescia, Italy.
OBJECTIVE: To compare the oncologic outcomes of nephron-sparing surgery versus
radical nephrectomy in intracapsular renal cell carcinoma (RCC) up to 7cm by
reviewing surgical experience retrospectively. METHODS: Data from 1290
consecutive patients who had surgery for RCC have been stored in a dedicated
database since 1983. We selected and reviewed those related to disease-free
patients who had been treated for unilateral pT1a/pT1b pN0/Nx M0 carcinomas up
to 7cm and later followed for a minimum of 12 mo. RESULTS: A total of 642
patients with mean follow-up of 72.9 mo were selected; 313 had been treated for
tumours <4cm in diameter (176 nephron-sparing surgery, 137 nephrectomy), whereas
329 had been treated for tumours measuring >/=4cm (52 nephron-sparing surgery,
277 nephrectomy). The comparison between tumours <4cm or >/=4cm in diameter
showed worse progression and disease-free survival rates for the latter, but the
type of surgery (nephron-sparing or radical) seemed to have
no significant impact. CONCLUSIONS: Conservative management can be cautiously
suggested for RCC up to 7cm because the worsening of prognosis as diameter
increases shows no statistical differences for either nephron-sparing or radical
surgery. The agreement of our results with those of similar studies available in
the literature may suggest designing a prospective study to compare conservative
and more radical surgery in the management of RCC up to 7cm.
-----
Curr Treat Options Oncol. 2007 Aug 22; [Epub ahead of print]
Tyrosine Kinase Inhibitors and Anti-Angiogenic Therapies in
Kidney Cancer.
Haas NB, Uzzo RG.
The Department of Medical Oncology, Fox Chase Cancer Center, Temple University
School of Medicine, 333 Cottman Avenue, Philadelphia, PA, 19111, USA.
OPINION STATEMENTS: Renal cell carcinoma (RCC) is a heterogeneous disease as
reflected in its presentation and clinical course, pathological subtypes,
nuclear grades and molecular biology. Emerging data indicate that renal tumors
express a variety of molecular tumor markers and unique patterns of gene
expression. Clinically the disease behaves quite heterogeneously, with courses
ranging from indolent to highly aggressive. Surgical monotherapy or as part of a
multimodal approach remains the standard of care for most cases of RCC. Radical
or partial nephrectomy is associated with a 5-year cancer specific survival (CSS)
of 85-97% for pT1 tumors. Unfortunately, 20% of patients have either locally
advanced or node positive (N+) RCC while another 22% have metastatic RCC (mRCC)
at presentation. Unlike the outcomes in early localized disease, survival rates
for N+ patients are poor and patients with mRCC are rarely cured despite
aggressive multimodal therapy. Classic cytotoxic chemo therapy has repeatedly
been shown to have little effect and only 5-20% of patients with mRCC respond to
immunologic agents such as interferon and/or interleukin. Cytoreductive
nephrectomy with systemic immunotherapy is associated with few cures with median
survivals of 12-24 months. Recent advances in our understanding of the molecular
origins and pathways of RCC have led to the development of more effective
targeted therapies. Here we review the molecular pathways that define the
pertinent therapeutic targets in RCC and the clinical data for these new and
promising agents.
-----
Nat Clin Pract Oncol. 2007 Aug;4(8):470-9.
Drug insight: advances in renal cell carcinoma and the role of
targeted therapies.
Larkin JM, Chowdhury S, Gore ME.
Royal Marsden Hospital, London, UK.
In metastatic renal cell carcinoma (RCC) immunotherapy results in a small but
important improvement in overall survival, but a need exists to develop
more-effective systemic therapies. Recent developments in our understanding of
the molecular biology of RCC have identified several pathways associated with
the development of the disease. A number of strategies designed specifically to
target these pathways have resulted. Initial studies have shown marked clinical
benefits of so-called 'targeted therapies'. Sunitinib, sorafenib and axitinib
are kinase inhibitors that inhibit the VEGF, platelet-derived growth factor and
c-kit receptor tyrosine kinases. Bevacizumab is a monoclonal antibody that is
directed against VEGF. Temsirolimus inhibits the mammalian target of rapamycin.
These agents have all shown considerable activity with manageable toxicity in
phase II and III studies in both previously treated and untreated patients. In
phase III studies, sorafenib and bevacizumab have been associated with prolonged
progression-free survival compared with placebo. Phase III data have shown
improvements in progression-free and overall survival with sunitinib and
temsirolimus, respectively, compared with interferon alfa. Additional studies
are needed to determine the optimum utilization of these agents at the
appropriate stage of disease and in the best combinations for maximal clinical
benefit.
-----
Anticancer Res. 2007 Jul-Aug;27(4C):2985-8.
Efficacy of IL-2 immunotherapy in metastatic renal cell carcinoma
in relation to the psychic profile as evaluated using the Rorschach test.
Messina G, Lissoni P, Bartolacelli E, Fumagalli L, Brivio F, Colombo E, Gardani
GS.
Division of Radiation Oncology, San Gerardo Hospital, 20052 Monza, Milan, Italy.
giusy.messina@libero.it
BACKGROUND: Despite the well-documented importance of the psycho-emotional
status in modulating the anticancer immunity, at present no study has been
performed to analyse the influence of the psychological condition on the
efficacy of IL-2 cancer immunotherapy. Previous clinical studies have already
suggested that the evidence of anxiety may negatively affect the therapeutic
efficacy of IL-2 immunotherapy of cancer. Moreover, previous psycho-oncological
investigations showed that the suppression of sexual pleasure and sexual
identity would represent one of the most frequent psychological profiles in
cancer patients. On this basis, a study was planned in an attempt to evaluate
relations existing between psychological status, analysed using the Rorschach
test and efficacy of IL-2 immunotherapy in the treatment of metastatic renal
cell cancer patients. PATIENTS AND METHODS: The study included 30 consecutive
metastatic RCC patients. IL-2 was injected s.c. at a dose of 3 million IU
twice/day 5 days/week for 4 consecutive weeks, corresponding to one complete
immunotherapeutic cycle, followed by a second cycle after a 21-day rest period.
RESULTS: A complete response (CR) was achieved in only 1/30 (3%) patients; a
partial response (PR) was obtained in 6/30 (20%) patients. The tumor response
rate (CR +PR) was 7/30 (23%) patients. The performance of a psychological
analysis was accepted by 24/30 (80%) patients. A normal sexual identity was
present in 7/24 (29%) patients. The tumor response rate achieved in patients
with sexual identity was significantly higher compared to these who had no
sexual identity or who refused the psychological investigation (p<0.05 and
p<0.01, respectively). In the same way, the increase in mean lymphocyte number
obtained in patients with sexual identity was significantly higher compared to
that found in the other two groups of patients. CONCLUSION: This study
demonstrated that the psychological status prior to treatment may be associated
with the clinical response to IL-2 cancer immunotherapy.
-----
J Endourol. 2007 Jul;21(7):709-13.
Nephron-Sparing Surgery and Percutaneous Biopsies in Renal-Cell
Carcinoma: A Global Impression among Endourologists.
Kümmerlin IP, Borrego J, Wink MH, Van Dijk MM, Wijkstra H, de la Rosette JJ,
Laguna MP.
Department of Urology, Academic Medical Center, University of Amsterdam, The
Netherlands.
Background and Purpose: On the one hand, nephron-sparing surgery (NSS) in small
renal tumors is a safe and effective alternative to radical nephrectomy. On the
other hand, the role of preoperative percutaneous needle biopsies (PNB) remains
controversial. The purpose of this study was to evaluate the global current use
of NSS in the treatment of renal-cell carcinoma (RCC) and the use of PNB among
endourologists. Materials and Methods: One thousand questionnaires were
distributed during the 23rd World Congress of Endourology and SWL. Six questions
regarding NSS and two questions regarding PNB were presented. Two hundred
twenty-two questionnaires were returned. Results: Of the respondents, 86.6%
perform NSS for small renal tumors, whereas 13.4% perform only radical
nephrectomies; 7.5% will consider NSS only in patients with a solitary kidney,
and 0.5% will never consider NSS. The techniques for NSS, in descending order of
preference, are partial nephrectomy, enucleation, cryoablation, radiofrequency
ablation, and high-intensity focused ultrasound. The mean and maximum diameter
of the tumor in patients with a normal contralateral kidney for which the
urologists perform NSS is 4.0 cm. For a centrally located tumor, NSS is an
option for 27.2% of the respondents. Regarding PNB in patients with suspicion of
RCC, 55.9% of respondents never obtain renal biopsies in the preoperative
assessment and 41.8% obtain them only in rare cases. The majority (90%) prefer
histologic over cytologic biopsies. Conclusions: Nephron-sparing surgery is
evolving to a global worldwide standard treatment for small renal tumors.
Percutaneous needle biopsy remains a highly debated procedure.
-----
Urology. 2007 Jul;70(1):43-6.
Laparoscopic radical nephrectomy with hilar lymph node dissection
in patients with advanced renal cell carcinoma.
Simmons MN, Kaouk J, Gill IS, Fergany A.
Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute,
Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
OBJECTIVES: Lymph node dissection (LND) may improve accuracy of staging,
decrease recurrence rates, and improve survival in patients with advanced renal
cell carcinoma (RCC). Here we assess the feasibility and safety of laparoscopic
LND. METHODS: Data were analyzed for patients who underwent combined
laparoscopic radical nephrectomy (LRN) with LND between July 1997 and September
2006. Demographics, operative data, pathologic data, outcomes, and complications
were assessed. RESULTS: In a cohort of 700 patients who underwent LRN, 14 (13
male, 1 female) underwent LND. Transperitoneal LRN was conducted in 12 patients
(86%). Retroperitoneal LRN and laparoscopic partial nephrectomy were conducted
in 1 patient each (7%). Lymph node dissection yielded an average of 2.7 lymph
nodes. Median tumor size was 9.5 cm (range, 1.5 to 13 cm), and median node size
was 2.3 cm (range, 0.8 to 11 cm). Tumor stage was T2 or higher in 9 cases (64%),
and distant metastasis was present in 7 patients (50%). One elective hand-assist
and one open conversion were performed. Median estimated blood loss was 250 mL
(range, 100 to 2100 mL). Median length of hospital stay was 2.5 days (range, 2
to 5 days). Median operative time was 199 minutes (range, 152 to 260 minutes).
There was a single grade 1 complication (7%). CONCLUSIONS: Patients with
advanced or metastatic RCC may require cytoreductive nephrectomy for staging and
tumor debulking before secondary therapy. Laparoscopic LND is both feasible and
safe in select patients. Decreased morbidity associated with the laparoscopic
approach is beneficial to patients with advanced disease.
-----
Proc (Bayl Univ Med Cent). 2007 Jul;20(3):244-8.
Targeted therapy for renal cell carcinoma: a new treatment
paradigm.
Hutson TE.
Genitourinary Oncology Program, Department of Oncology, Baylor Charles A.
Sammons Cancer Center, Dallas, Texas.
Metastatic clear cell renal cell cancer has traditionally been treated with
cytokines (interferon or interleukin-2). Improved understanding of biology has
engendered novel targeted therapeutic agents that have altered the natural
history of this disease. The vascular endothelial growth factor and its related
receptor and the mTOR signal transduction pathway have particularly been
exploited. Sunitinib malate, sorafenib tosylate, temsirolimus, and bevacizumab
have improved clinical outcomes in randomized trials. Other multitargeted
tyrosine kinase inhibitors (lapatinib, axitinib, pazopanib) and antiangiogenic
agents (VEGF Trap, lenalidomide) have also demonstrated activity in early
studies. Combinations of these agents are being evaluated. The future of the
therapy of renal cancer appears promising owing to the efficacy of these novel
agents.
-----
ScientificWorldJournal. 2007 Apr 9;7:837-49.
Cytokine-based immunotherapy for advanced kidney cancer: past
results and future perspectives in the era of molecularly targeted agents.
Porta C, Paglino C, Imarisio I, Bonomi L.
Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia,
Italy. c.porta@smatteo.pv.it
Until recently, immunotherapy has been the only therapeutic option available for
patients with advanced kidney cancer, even though different choices were often
made on the two sides of the Atlantic Ocean. The absence of alternatives made
different immunotherapeutic approaches common practice, even with few adequate
randomized studies that addressed key questions, such as the best treatment and
schedule, and so on. The recent registration of the first two, molecularly
targeted, agents Sorafenib and Sunitinib could (and will) render many
therapeutic approaches, e.g., single-agent Interferon, obsolete. In this review,
we shall cover the past achievements obtained so far with cytokine-based
immunotherapy and discuss the present role of immunotherapy in the era of
molecularly targeted agents. In particular, specific indications for
immunotherapy are emerging (e.g., the use of Interleukin-2 in patients with high
CAIX expression), while new trials are ongoing to test immunotherapy i
n combination with molecularly targeted agents, such as Sorafenib, Sunitinib, or
Bevacizumab.
-----
Urology. 2007 Apr;69(4):642-5; discussion 645-6.
Superselective embolization as first step of laparoscopic partial
nephrectomy.
Gallucci M, Guaglianone S, Carpanese L, Papalia R, Simone G, Forestiere E,
Leonardo C.
Department of Urology, Regina Elena Cancer Institute, Rome, Italy. gallucci@ifo.it
OBJECTIVES: Laparoscopic partial nephrectomy is currently very hard to perform
because of the great difficulty in obtaining renal parenchymal hemostasis during
tumor excision and the consequent high risk of bleeding. The aim of this study
was to propose a method to decrease the risk of bleeding, consisting of the
superselective embolization of tumor vessels before performing the laparoscopic
partial nephrectomy. METHODS: Fifty patients with small, solitary, enhancing,
predominantly exophytic renal tumors underwent a superselective radiographically
guided embolization of tumor vessels. An average of 6 hours after embolization,
the patients underwent partial laparoscopic nephrectomy, with transperitoneal
access and three trocars placed, under balanced general anesthesia. The mean
operative time was measured, as was the mean estimated blood loss. RESULTS: The
mean operative time was 90 minutes, the mean estimated blood loss was 200 mL,
and the average hospital stay was 6 days. Complications were reported in only 2
patients. The final pathologic evaluation confirmed the diagnosis of renal cell
carcinoma in 43 cases. The median follow-up was 11 months and, to date, the
examinations have revealed no recurrences in any of the cases. CONCLUSIONS:
Superselective embolization is a valid option for laparoscopic partial
nephrectomy. The procedure does not require any regional vascular control or
clamping, reduces the estimated blood loss, and reduces the operative time.
-----
Clin Orthop Relat Res. 2007 Apr 12; [Epub ahead of print]
Radiotherapy to Bone Has Utility in Multifocal Metastatic Renal
Carcinoma.
Reichel LM, Pohar S, Heiner J, Buzaianu EM, Damron TA.
>From the *Department of Orthopedics and Radiation Oncology, Upstate Medical
University, State University of New York, Syracuse, NY; the daggerDepartment of
Orthopedics, University of Wisconsin, Madison, WI; and the double daggerDept. of
Mathematics and Statistics, University of North Florida, Jacksonville, FL.
Renal cell carcinoma metastases to bone are classically considered
radioresistant. We reviewed 28 patients who underwent irradiation for metastatic
renal cell carcinomas to bone to test the hypothesis that irradiation of renal
metastases to bone provides adequate palliation in carefully selected patients.
Metastases were multifocal in all patients. All patients were followed until
death. Overall, 36 index radiotherapy treatments were given as palliative
initial treatment for 36 osseous metastatic sites. Twenty-five of 36 sites
(69.5%) had no subsequent radiotherapy. Eight sites (22.2%) underwent repeat
radiotherapy at a mean 28.9 weeks after treatment. Two (5.6%) additional sites
underwent surgery at the site at an average 74 weeks later, and a pathologic
fracture occurred at one (2.8%) site 3 weeks after irradiation. Overall, 33 of
36 (91.7%) sites had only radiotherapy as their source of palliation. Median
times to return to pretreatment pain and functional levels, however, were 2
months and 1 month, respectively. Radiotherapy to osseous sites appears to
control pain for the short term and generally prevents fractures and avoids the
need for surgery in renal cell carcinoma patients with multiple bone
metastases.Level of Evidence: Level IV, therapeutic study. See the Guidelines
for Authors for a complete description of levels of evidence.
-----
Cancer. 2007 Apr 9; [Epub ahead of print]
Renal cell carcinoma clinically involving adjacent organs:
experience with aggressive surgical management.
Margulis V, Sanchez-Ortiz RF, Tamboli P, Cohen DD, Swanson DA, Wood CG.
Department of Urology, University of Texas M. D. Anderson Cancer Center,
Houston, Texas.
BACKGROUND.: Historically, patients with nonmetastatic renal cell carcinoma (RCC)
involving adjacent organs have been considered inoperable and incurable. The
oncologic efficacy of an aggressive surgical approach was evaluated in a
selected subpopulation of RCC patients. Further, an attempt was made to define
the clinical and pathologic characteristics predictive of surgical failure.
METHODS.: With Institutional Review Board approval, the institutional
nephrectomy database of 3470 patients treated at MD Anderson Cancer Center from
1990 to 2006 was searched for RCC patients treated with radical nephrectomy and
resection of at least 1 adjacent organ thought to be directly involved by RCC.
Patients with nonmetastatic RCC and a minimum follow-up of 6 months were
included in the analysis. RESULTS.: In all, 30 patients with clinical T4NxM0 RCC
and median follow-up of 32.3 months (range, 8.5-140.1) met the study inclusion
criteria and comprise the dataset for the analysis. On pathologic evaluation 60%
of patients were clinically overstaged, as only 12 (40%) of 30 patients
demonstrated direct invasion into adjacent organs resected. None of the clinical
tumor characteristics predicted a finding of pathologic T4 RCC. Nodal
involvement and pathologic T stage were significant independent predictors of
disease recurrence (hazard ratio [HR] 3.726, P = .043, and HR 2.414, P = .045,
respectively) and cancer-specific survival (HR 17.145, P = .002, and HR 3.791, P
= .024, respectively). Disease recurred in 11 of 18 (61.1%) of <pT4 patients and
in 10 of 12 (83.3%) of pT4 patients at a median 13.3 and 2.3 months,
respectively; 13 (73.3%) <pT4 patients and 5 (41.7%) pT4 patients were alive at
the time of analysis. CONCLUSIONS.: True pathologic involvement of adjacent
organs by RCC cannot be predicted from pre- or intraoperative parameters. A
significant proportion of patients clinically suspected of having T4 RCC are
downstaged, and benefit from aggressive surgical resection with en bloc removal
of involved organs. Cancer 2007. (c) 2007 American Cancer Society.
-----
CA Cancer J Clin. 2007 Mar-Apr;57(2):112-25.
Recent progress in the management of advanced renal cell
carcinoma.
Garcia JA, Rini BI.
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University,
Cleveland, OH.
A better understanding of the molecular biology of renal cell carcinoma (RCC)
has led to a dramatic paradigm shift in the treatment of patients with
metastatic disease. Historically, a nonspecific immune approach using cytokines
was employed, but recently this has transitioned to a molecularly-targeted
approach against vascular endothelial growth factor (VEGF) and related pathways.
Several anti-VEGF agents, including ligand-binding agents such as bevacizumab
and the small molecule inhibitors of VEGF and related receptors such as
sunitinib and sorafenib, have demonstrated clinical activity in patients with
metastatic RCC. Other agents that inhibit alternative targets such as the
mammalian target of rapamycin (mTOR) have also demonstrated activity. This
generation of novel molecular targeted therapies continues to show great
promise. The purpose of this review is to summarize the current management and
to discuss potential future directions in the management of metastatic RCC.
-----
Invest New Drugs. 2007 Mar 28; [Epub ahead of print]
Phase II study of Triapine(R) in patients with metastatic renal
cell carcinoma: a trial of the National Cancer Institute of Canada Clinical
Trials Group (NCIC IND.161).
Knox JJ, Hotte SJ, Kollmannsberger C, Winquist E, Fisher B, Eisenhauer EA.
Department of Medical Oncology, University Health Network-OCI/Princess Margaret
Hospital, 610 University Avenue, Toronto, ON, M5G 2M9, Canada, jennifer.knox@uhn.on.ca.
Triapine(R) is a novel small molecule ribonucleotide reductase inhibitor that
showed activity in renal cell carcinoma (RCC) cell lines. Evaluating new agents
with novel mechanisms remains of interest for patients with incurable RCC. This
was a single-arm, multicentre phase II trial where Triapine was given at a
schedule of 96 mg/m(2) 2-h infusion daily x 4 repeated every 2 weeks in patients
with recurrent RCC. A median of four cycles of Triapine was administered to 19
eligible patients. One response was seen (7%.) Median time to progression was
3.6 months. Common adverse events (AEs) were grade 1-2, with fatigue in 74%,
nausea in 68% and vomiting in 58%. However grade 3/4 neutropenia was seen in 79%
and acute reactions of hypoxia, hypotension, methemoglobinemia were seen. Dose
reductions/delays due to AEs were common with only 47% of patients receiving >
90% of planned dose intensity. The study closed, at the end of stage 1 as it did
not meet the minimal efficacy criteria to proceed. Further evaluation of
Triapine at this dose and schedule in patients with advanced kidney cancer is
not recommended.
-----
Urology. 2007 Mar;69(3):462-4.
Renal cell carcinoma in renal transplant patients.
Ianhez LE, Lucon M, Nahas WC, Sabbaga E, Saldanha LB, Lucon AM, Srougi M.
Department of Urology, Sao Paulo University Medical School, Sao Paulo, Sao
Paulo, Brazil.
OBJECTIVES: To report our experience with renal cell carcinoma in patients with
end-stage renal failure receiving dialysis at two institutions that perform a
large number of transplantations. Renal cell carcinoma is more frequent in
patients with end-stage renal failure treated with dialysis and in renal
transplant patients than in the population at large. METHODS: We reviewed the
case histories of 1375 consecutive patients who had transplanted kidneys
functioning for more than 1 year. RESULTS: Eleven renal tumors were found in 10
patients (1.37%); 10 of the tumors (90%) were in the native kidney (9 unilateral
and 1 bilateral) and 1 (10%) was in the transplanted kidney. The tumors in the
native kidneys were discovered incidentally. Three were in organs removed for
treatment of arterial hypertension and the other seven were found by
ultrasonography. The tumor in the transplanted kidney was found after
nephrectomy for the treatment of hematuria. The tumor types were clear cell in
six, papillary in four, and chromophobe in one. Of the 9 patients who were
treated with radical nephrectomy, 7 were alive with no evidence of the disease
and 2 had died of other causes, also with no evidence of the disease. One
patient who already had metastases at the diagnosis did not undergo surgery and
died 4 months later. CONCLUSIONS: The native kidneys of renal transplant
patients should be examined by ultrasonography annually because they are at
greater risk of renal cell carcinoma. Radical nephrectomy cures those cases in
which the tumors are clinically localized and 6 cm or less in size.
-----
Scand J Urol Nephrol. 2007;41(1):10-3.
Nephron-sparing surgery for renal cell carcinoma in the solitary
kidney.
Berdjis N, Hakenberg OW, Novotny V, Manseck A, Oehlschlager S, Wirth MP.
Department of Urology, University Hospital Carl Gustav Carus, Technical
University Dresden, Dresden, Germany.
OBJECTIVE: Partial nephrectomy in solitary kidneys carries the risk of tumour
progression as well as loss of renal function. We evaluated complications and
outcome in patients with renal cell cancer in solitary kidneys who were treated
by means of nephron-sparing surgery. MATERIAL AND METHODS: Between 1993 and
2003, 38 patients with renal cell carcinoma in a solitary kidney underwent
nephron-sparing surgery (partial nephrectomy, n = 37; work-bench resection, n =
1). Of these patients, 21 had asynchronous and eight had synchronous bilateral
tumours and underwent contralateral radical nephrectomy. The variables examined
were tumour size, disease progression, pre- and postoperative renal function and
early (within 30 days of nephron-sparing surgery) and late complications.
RESULTS: After a mean follow-up period of 41.7 months (range 8-93 months) the
mean serum creatinine level had increased from 1.25 mg/dl preoperatively to 1.62
mg/dl postoperatively. Seventeen patients retained normal renal function and 21
developed some degree of renal insufficiency. New-onset chronic renal
insufficiency after nephron-sparing surgery with creatinine levels >2 mg/dl was
the only late complication observed, occurring in 10 cases. None of the patients
required dialysis. Transient urinary leakage was the most frequent early
complication, occurring in four cases. Recurrence and/or progression were seen
in six patients: four with local recurrence (three of whom also had distant
metastases) and two with pure metastatic progression. Nephron-sparing surgery
was repeated for the patient with isolated local tumour recurrence. The mean
tumour size was 3.8 cm (range 0.7-9.9 cm). Tumour size was markedly greater in
patients who developed disease progression (6.2 vs 3.5 cm) and in those who
developed renal insufficiency (5.2 vs 3.3 cm). CONCLUSIONS: Nephron-sparing
surgery for renal cell carcinoma involving a solitary kidney provides effective
curative treatment for small tumours, with preservation of renal function.
However, patients who undergo partial nephrectomy for locally extensive tumours
are at high risk of disease progression.
-----
J Endourol. 2007 Jan;21(1):71-4.
Laparoscopic partial nephrectomy: experience in 60 cases.
Brown GA, Matin SF.
Department of Urology, The University of Texas M. D. Anderson Cancer Center,
Houston, Texas.
Purpose: To identify the factors associated with better outcomes in patients
undergoing laparoscopic partial nephrectomy (LPN). Patients and Methods: We
retrospectively analyzed the medical records of 36 men and 24 women aged 31 to
80 years (mean 60 years) in whom LPN was attempted at our institution over a
3.5-year period. Baseline patient characteristics and operative, pathologic, and
postoperative outcomes were analyzed. The median duration of follow-up was 14.2
months (range 1-38 months). Results: The median pathologic tumor size was 2.1 cm
(range 0.7-6.0 cm). Final pathologic review revealed renal-cell carcinoma in 73%
of patients. Six patients (10%) required conversion to either an open partial
nephrectomy or a laparoscopic radical nephrectomy. Dense perinephric adipose
tissue in the setting of a small renal tumor and unanticipated multifocal
disease were factors associated with surgical conversion. The median overall
estimated blood loss was 112 mL, and the median warm-ischemia time was 30
minutes. Blood loss was greater in patients who did not undergo hilar clamping
(467 v 65 mL; P = 0.008). Conclusion: Factors influencing successful LPN
outcomes include selecting a tumor commensurate with the surgeon's laparoscopic
experience, performing routine hilar clamping, adjunctive use of hemostatic
agents, and renal-parenchymal suture ligation. The presence of thick, fibrotic
perinephric fat overlying a small tumor increases the technical difficulty.
-----
Clin Cancer Res. 2007 Jan 15;13(2):747s-52s.
Sorafenib in renal cell carcinoma.
Flaherty KT.
Author's Affiliation: Abramson Cancer Center, University of Pennsylvania,
Philadelphia, Pennsylvania.
Sorafenib is an orally available inhibitor of vascular endothelial growth factor
receptors, platelet-derived growth factor receptor-beta, and RAF kinases. A dose
of 400 mg twice daily administered continuously was selected for phase 2
testing, although 600 mg twice daily formally met criteria for a maximum
tolerated dose. It is well tolerated compared with cytokine therapy. Antitumor
activity was shown clearly in the context of a randomized discontinuation phase
2 trial. In this setting, even disease stabilization was established as a
treatment-related phenomenon. A phase 3 trial with sorafenib confirmed a benefit
of therapy across the vast majority of patients treated with sorafenib as
opposed to placebo. Limited investigations into the mechanism of action of
sorafenib in renal cell carcinoma support vascular endothelial growth factor
receptor antagonism as the primary mediator of effect. The toxicity profile of
sorafenib allows for its use in combination regimens. The focus of efforts to
improve on the efficacy of sorafenib is on use with IFN, bevacizumab, or
temsirolimus. Preliminary evidence with this approach is promising and will be
the subject of the next generation of randomized trials in renal cell carcinoma.
-----
Clin Cancer Res. 2007 Jan 15;13(2):716s-20s.
Update on the application of interleukin-2 in the treatment of
renal cell carcinoma.
McDermott DF.
Author's Affiliation: Beth Israel Deaconess Medical Center and the
Dana-Farber/Harvard Cancer Center Renal Cancer Program, Boston, Massachusetts.
High-dose bolus interleukin 2 (IL-2) was granted Food and Drug Administration
approval based on its ability to produce durable complete responses in a small
number of patients with metastatic renal cell carcinoma. Results from randomized
phase 3 trials suggest that regimens involving lower doses of IL-2, either alone
or in combination with IFN, produce fewer tumor regressions of less overall
quality. Given the toxicity, expense, and limited efficacy of this treatment,
recent studies have focused on identifying predictors of response (or
resistance) to IL-2 therapy. This year, investigators launched a clinical trial
designed to prospectively determine if patients who are more likely to respond
to high-dose IL-2 can be identified before starting therapy. As the list of
effective therapies for metastatic renal cell carcinoma grows, improvements in
patient selection will be necessary to ensure that patients who might attain a
durable remission with IL-2 will not miss this opportunity.
-----
Clin Cancer Res. 2007 Jan 15;13(2):697s-702s.
Multimodal approaches in the management of locally advanced and
metastatic renal cell carcinoma: combining surgery and systemic therapies to
improve patient outcome.
Wood CG.
Author's Affiliation: The University of Texas M. D. Anderson Cancer Center,
Houston, Texas.
Patients with locally advanced renal cell carcinoma are at high risk of
metastatic relapse following surgery. Patients with metastatic disease have a
poor prognosis and few systemic therapy options. Radiation, chemotherapy,
hormonal therapy, vaccines, and immunotherapy have all been tested as adjuvant
therapy without benefit. Neoadjuvant therapy in the metastatic setting holds
promise as a new treatment paradigm. It can serve as a litmus test to allow
proper patient selection for aggressive surgical intervention and may provide
limited downstaging of primary tumors in selected cases. It can also provide a
histologic assessment of the effect of targeted therapy. Application of this
paradigm may have merit in the locally advanced setting as well. Effective
adjuvant therapy for renal cell carcinoma remains elusive. The benefit of new
targeted therapies has yet to be tested in this setting. Neoadjuvant strategies
that integrate aggressive surgical intervention with systemic therapy may hold
promise as a treatment paradigm.
-----
Clin Cancer Res. 2007 Jan 15;13(2):693s-6s.
Cytoreductive nephrectomy for metastatic renal cell carcinoma: is
it still imperative in the era of targeted therapy?
Pantuck AJ, Belldegrun AS, Figlin RA.
Authors' Affiliation: Departments of Urology and Medicine, David Geffen School
of Medicine at University of California at Los Angeles, Los Angeles, California.
In the era before cytokine therapy, controversy existed about the need for
cytoreductive nephrectomy in treating patients with metastatic renal cell
carcinoma. In 1978, Dekernion showed that nephrectomy alone had no effect on
survival. During this period, removal of the malignant kidney was confined to
palliative therapy in some settings of metastatic RCC, such as pain related to
the kidney mass, intractable hematuria, erythrocytosis, uncontrolled
hypertension, or poorly controlled hypercalcemia. When interleukin-2 was
approved by the Food and Drug Administration in 1992, the role of nephrectomy
was reexamined. After a decade of controversy, two randomized controlled studies
established that cytoreductive surgery has a role in properly selected patients
and offers a survival advantage when done before cytokine therapy.
Unfortunately, the mechanisms underlying this benefit remain poorly understood.
Immunotherapy may work best when there is a small volume of cancer present, and
removing a large primary tumor may prevent the seeding of additional metastases.
Data have also suggested that primary tumors were capable of producing
immunosuppressive compounds that might decrease the efficacy of immunotherapy.
Another hypothesis suggested that removing the kidney altered the acid/base
status of the patient to such an extent that the growth of the tumor was
hindered. With the emergence in 2006 of two targeted agents for advanced renal
cell carcinoma, the role of cytoreductive nephrectomy has reemerged as a source
of controversy. Although evidence-based medical practice suggests a role for
nephrectomy before the use of targeted agents, the arguments for and against
this practice will be weighed.
-----
Curr Urol Rep. 2007 Jan;8(1):19-30.
Adjuvant therapy for high-risk renal cell carcinoma patients.
Kunkle DA, Haas NB, Uzzo RG.
Department of Urologic Oncology, Fox Chase Cancer Center, 333 Cottman Avenue,
Philadelphia, PA 19111, USA. R_Uzzo@FCCC.edu
For most cases of renal cell carcinoma (RCC), the standard of care is surgical
resection as monotherapy or as part of a multimodal approach. In patients with
early localized disease, radical nephrectomy is associated with a favorable
prognosis, whereas patients with advanced disease are rarely cured. A
significant number of patients undergoing surgery for localized RCC experience
recurrence, suggesting that there are some individuals in whom surgical excision
is necessary but insufficient. In these patients, the development of effective
adjuvant strategies is imperative. In this article, we review the prognostic
variables and comprehensive staging algorithms for identifying patients at high
risk for disease recurrence. Additionally, we review data from completed
adjuvant RCC trials and highlight relevant ongoing trials.
-----
Oncology (Williston Park). 2006 Dec;20(14):1745-53; discussion 1756.
Novel targets and therapies for metastatic renal cell carcinoma.
Feldman DR, Motzer RJ.
Division of Medical Oncology and Hematology, Department of Internal Medicine,
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
For the past 20 years, the systemic treatment of metastatic renal cell carcinoma
(RCC) has been limited primarily to cytokines, with few patients showing
benefit. However, recent advances in understanding the pathobiology of RCC have
led to the identification of novel therapeutic targets for this disease. Drugs
specifically designed to inhibit these targets have been developed, with several
showing superior efficacy over traditional cytokine therapy. Moreover, these
agents are well tolerated and have improved the span of progression-free, and in
some cases, overall survival. As a result, between December 2005 and January
2006, two of these targeted therapies--sunitinib (Sutent) and sorafenib (Nexavar)--were
approved by the U.S. Food and Drug Administration for the treatment of advanced
RCC. The authors review the clinical trials that have focused on these two drugs
as well as those concentrating on two other promising agents, bevacizumab (Avastin)
and temsirolimus. The ways in which these novel drugs are changing the standard
of care for metastatic RCC and the future directions of RCC clinical trials are
also discussed.
-----
Clin Genitourin Cancer. 2006 Dec;5 Suppl 1:S24-30.
Improving outcomes with novel therapies for patients with newly
diagnosed renal cell carcinoma.
Speca J, Yenser S, Creel P, George D.
Division of Medical Oncology, Department of Medicine, Duke University Medical
Center, Durham, NC.
With the approval of sunitinib and sorafenib, 2 new multitargeted tyrosine
kinase inhibitors, for the treatment of advanced renal cell carcinoma (RCC), the
natural history and prognosis of patients with this disease has significantly
improved. These drugs were approved based upon clinical data demonstrating
robust, unprecedented response rates in one case and dramatic prolongation of
progression-free survival in the other. In both cases, these results were seen
in study patients in whom standard therapy had failed and who, on average,
carried substantial disease burden. Important challenges today include
integrating these therapies with other standard therapeutic options and into
other advanced-stage RCC patient populations. This article addresses current
data and practice patterns regarding the clinical use of tyrosine kinase
inhibitors in patients with advanced-stage RCC, including dose modifications and
alternative dosing, the current role of debulking nephrectomy, and use in
patients with indolent disease. Finally, a summary of the more common side
effects and management strategies for these is also discussed. Ultimately, more
clinical data is needed to address the chronic use of these agents alone, in
combination with other agents, with radiation therapy, and in sequence.
Previous Renal Cell Carcinoma
Research: 2002-2006
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