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Previous Lung Cancer Research: 2002-2006   
The Lung Cancer File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Lung Cancer, click HERE.
 

Latest Research on Lung Cancer
     
Int J Cancer. 2008 Sep 1;123(5):1173-80.
Dietary alpha-, beta-, gamma- and delta-tocopherols in lung cancer risk.
Mahabir S, Schendel K, Dong YQ, Barrera SL, Spitz MR, Forman MR.
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Studies of vitamin E and cancer have focused on the alpha-tocopherol form of the vitamin. However, other forms of vitamin E, in particular gamma-tocopherol may have unique mechanistic characteristics relevant to lung cancer prevention. In an ongoing study of 1,088 incident lung cancer cases and 1,414 healthy matched controls, we studied the associations between 4 tocopherols (alpha-, beta-, gamma-, and delta-tocopherol) in the diet and lung cancer risk. Using multiple logistic regression analysis, the adjusted odds ratios (OR) and 95% confidence intervals (CI) of lung cancer for increasing quartiles of dietary alpha-tocopherol intake were 1.0, 0.63 (0.50-0.79), 0.58 (0.44-0.76) and 0.39 (0.28-0.53), respectively (p-trend < 0.0001). For dietary intake of beta-tocopherol, the OR and 95% CI for all subjects were: 1.0, 0.79 (0.63-0.98), 0.59 (0.45-0.78) and 0.56 (0.42-0.74), respectively (p-trend < 0.0001). Similar results for dietary gamma-tocopherol intake were observed: 1.0, 0.84 (0.67-1.06), 0.76 (0.59-0.97) and 0.56 (0.42-0.75), respectively (p- trend = 0.0002). No significant association between delta-tocopherol intake and lung cancer risk was detected. When the 4 tocopherols were summed as total tocopherol intake, a monotonic risk reduction was also observed. When we entered the other tocopherols in our model, only the association with dietary alpha-tocopherol intake remained significant; i.e., increasing intake of dietary alpha-tocopherol accounted for 34-53% reductions in lung cancer risk. To the best of our knowledge, this is the first report of the independent associations of the 4 forms of dietary tocopherol (alpha-, beta-, gamma- and delta-tocohperol) on lung cancer risk. Given the limitations with case-control studies, these findings need to be confirmed in further investigations.

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Int J Cancer. 2008 Aug 15;123(4):753-9.
The role of PGP9.5 as a tumor suppressor gene in human cancer.
Tokumaru Y, Yamashita K, Kim MS, Park HL, Osada M, Mori M, Sidransky D.
Department of Otolaryngology, Head and Neck Cancer Research Institute, Johns Hopkins University, Baltimore, MD, USA.

PGP9.5 is a controversial molecule from an oncologic point of view. We recently identified frequent methylation of PGP9.5 gene exclusively in primary head and neck squamous cell carcinoma (HNSCC), suggesting that it could be a tumor suppressor gene. On the other hand, PGP9.5 was reported to be overexpressed in a subset of human cancers presumably due to intrinsic oncogenic properties or as a result of transformation. To demonstrate that PGP9.5 possesses tumor suppressive activity, we examined forced expression by stable transfection of PGP9.5 in 4 HNSCC cell lines. Although all 4 cell lines demonstrated reduced log growth rates in culture after transfection, only 2 cell lines with wild type p53 (011, 022) demonstrated decreased growth in soft agar. In 2 cell lines with mutant p53 (013, 019), we observed no altered growth in soft agar and increased sensitivity to UV irradiation. We then tested for and found a high frequency of promoter methylation in a larger panel of primary tumors including HNSCC, esophageal SCC, gastric, lung, prostate and hepatocellular carcinoma. Our data support the notion that PGP9.5 is a tumor suppressor gene that is inactivated by promoter methylation or gene deletion in several types of human cancers. (c) 2008 Wiley-Liss, Inc.

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Cancer Invest. 2008 Aug;26(7):718-24.
The effect of dalteparin, a kind of low molecular weight heparin, on lung adenocarcinoma A549 cell line in vitro.
Chen X, Xiao W, Qu X, Zhou S.
Department of Respiratory Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, PR China.

The beneficial effects of unfractionated heparin and low molecular weight heparin on cancer progression have been reported. In the study, the effect of dalteparin on pulmonary adenocarcinoma A549 cell line was observed in vitro. Our experiments revealed that: (1) dalteparin can inhibit the cell viability dose-dependently and time-dependently; (2) dalteparin can arrest the A549 cells in G(1) phase and induce them to early apoptosis; (3) dalteparin exerts its effects through p21(WAF1) and p27(KIP1) proteins; and (4) the changes of p21(WAF1) and p27(KIP1) proteins caused by dalteparin occurred at posttranscriptional levels.

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J Clin Oncol. 2008 Jul 20;26(21):3573-81.
Pooled analysis of the effect of age on adjuvant cisplatin-based chemotherapy for completely resected non-small-cell lung cancer.
Früh M, Rolland E, Pignon JP, Seymour L, Ding K, Tribodet H, Winton T, Le Chevalier T, Scagliotti GV, Douillard JY, Spiro S, Shepherd FA.
Department of Medical Oncology, Princess Margaret Hospital, Toronto. martin.frueh@kssg.ch

PURPOSE: This pooled analysis was undertaken to assess the efficacy and toxicity of adjuvant cisplatin-based chemotherapy in elderly patients with non-small-cell lung cancer (NSCLC). METHODS: We used individual patient data from 4,584 patients enrolled onto five trials of cisplatin-based chemotherapy who form the basis for the Lung Adjuvant Cisplatin Analysis (LACE) pooled analysis. Patient and treatment characteristics, overall and event-free survival, cause-specific mortality, chemotherapy toxicity and delivery were compared among three age groups: 3,269 young (71%; < 65), 901 midcategory (20%; 65 to 69), and 414 elderly patients (9%; >or= 70). Log-rank tests stratified by trials were used with a test for trend to study the effect of chemotherapy on survival according to age. RESULTS: The hazard ratio (HR) of death for the young patients was 0.86 (95% CI, 0.78 to 0.94), 1.01 for the midcategory (95% CI, 0.85 to 1.21), and 0.90 for elderly patients (95% CI, 0.70 to 1.16; test for trend: P = .29). The HR for event-free survival was 0.82 for young (95% CI, 0.75 to 0.90), 0.90 for the midcategory (95% CI, 0.76 to 1.06), and 0.87 for elderly patients (95% CI, 0.68 to 1.11; test for trend: P = .42). More elderly patients died from non-lung cancer-related causes (12% young, 19% midcategory, 22% elderly; P < .0001). No differences in severe toxicity rates were observed. Elderly patients received significantly lower first and total cisplatin doses, and fewer chemotherapy cycles (chi(2) P < .0001). CONCLUSION: Adjuvant cisplatin-based chemotherapy should not be withheld from elderly patients with NSCLC purely on the basis of age.

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J Clin Oncol. 2008 Jul 20;26(21):3560-6.
DNA damage and repair capacity in patients with lung cancer: prediction of multiple primary tumors.
Orlow I, Park BJ, Mujumdar U, Patel H, Siu-Lau P, Clas BA, Downey R, Flores R, Bains M, Rizk N, Dominguez G, Jani J, Berwick M, Begg CB, Kris MG, Rusch VW.
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. orlowi@mskcc.org

PURPOSE: Patients who survive one occurrence of non-small-cell lung cancer (NSCLC) are at higher risk of a second malignancy. Capacity to repair damaged DNA may modulate individual susceptibility to develop lung cancer. Therefore, we evaluated constitutive and induced DNA damage, and repair capacity, in patients with multiple NSCLCs (cases) and compared the results to those obtained in patients with a single NSCLC (controls). PATIENTS AND METHODS: One hundred eight cases and 99 controls matched by age, sex, and time since diagnosis were studied. DNA damage was assessed on peripheral blood lymphocytes by the comet assay before and after exposing cells to a tobacco-derived carcinogen, using the tail moment and the tail intensity as measures to assess baseline damage, induced damage and repair capacity. RESULTS: Constitutive DNA damage, benzo(a)pyrene diol epoxide-induced damage, and repair after BPDE-induced damage were all significantly higher in cases than in controls. These results were confirmed in regression analyses adjusted for potential confounders. CONCLUSION: DNA damage as measured by the comet assay is associated with the development of multiple primary tumors in individuals with NSCLC.

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J Clin Oncol. 2008 Jul 20;26(21):3552-9. Epub 2008 May 27.
Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group.
Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, Dunant A, Torri V, Rosell R, Seymour L, Spiro SG, Rolland E, Fossati R, Aubert D, Ding K, Waller D, Le Chevalier T; LACE Collaborative Group.
Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France. jppignon@igr.fr

PURPOSE: Several recent trials have shown a significant overall survival (OS) benefit from postoperative cisplatin-based chemotherapy in patients with non-small-cell lung cancer (NSCLC). The aim of the Lung Adjuvant Cisplatin Evaluation was to identify treatment options associated with a higher benefit or groups of patients who particularly benefit from postoperative chemotherapy. PATIENTS AND METHODS: Individual patient data were collected and pooled from the five largest trials (4,584 patients) of cisplatin-based chemotherapy in completely resected patients that were conducted after the 1995 NSCLC meta-analysis. The interactions between patient subgroups or treatment types and chemotherapy effect on OS were analyzed using hazard ratios (HRs) and log-rank tests stratified by trial. RESULTS: With a median follow-up time of 5.2 years, the overall HR of death was 0.89 (95% CI, 0.82 to 0.96; P = .005), corresponding to a 5-year absolute benefit of 5.4% from chemotherapy. There was no heterogeneity of chemotherapy effect among trials. The benefit varied with stage (test for trend, P = .04; HR for stage IA = 1.40; 95% CI, 0.95 to 2.06; HR for stage IB = 0.93; 95% CI, 0.78 to 1.10; HR for stage II = 0.83; 95% CI, 0.73 to 0.95; and HR for stage III = 0.83; 95% CI, 0.72 to 0.94). The effect of chemotherapy did not vary significantly (test for interaction, P = .11) with the associated drugs, including vinorelbine (HR = 0.80; 95% CI, 0.70 to 0.91), etoposide or vinca alkaloid (HR = 0.92; 95% CI, 0.80 to 1.07), or other (HR = 0.97; 95% CI, 0.84 to 1.13). Chemotherapy effect was higher in patients with better performance status. There was no interaction between chemotherapy effect and sex, age, histology, type of surgery, planned radiotherapy, or planned total dose of cisplatin. CONCLUSION: Postoperative cisplatin-based chemotherapy significantly improves survival in patients with NSCLC.

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J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. Comment in: J Clin Oncol. 2008 Jul 20;26(21):3485-6.
Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer.
Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D.
University of Torino, Department of Clinical and Biological Sciences, S. Luigi Hospital, Regione Gonzole, 10, Orbassano (Torino), Italy. giorgio.scagliotti@unito.it

PURPOSE: Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. PATIENTS AND METHODS: This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 (n = 863) or cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 (n = 862) every 3 weeks for up to six cycles. RESULTS: Overall survival for platin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P <or= .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common. CONCLUSION: In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

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J Clin Oncol. 2008 Jul 10;26(20):3351-7.
Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy.
Hirsch FR, Herbst RS, Olsen C, Chansky K, Crowley J, Kelly K, Franklin WA, Bunn PA Jr, Varella-Garcia M, Gandara DR.
Southwest Oncology Group, San Antonio, USA. Fred.Hirsch@UCHSC.edu

PURPOSE: Epidermal growth factor receptor (EGFR) gene copy number detected by fluorescent in situ hybridization (FISH) has proven to be useful for selection of non-small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors. Here, we evaluate EGFR FISH as a predictive marker in NSCLC patients receiving the EGFR monoclonal antibody inhibitor cetuximab plus chemotherapy. PATIENTS AND METHODS: Two hundred twenty-nine chemotherapy-naive patients with advanced-stage NSCLC were enrolled onto a phase II selection trial evaluating sequential or concurrent chemotherapy (paclitaxel plus carboplatin) with cetuximab. RESULTS: EGFR FISH was assessable in 76 patients with available tumor tissue and classified as positive (four or more gene copies per cell in >/= 40% of the cells or gene amplification) in 59.2%. Response (complete response/partial response) was numerically higher in FISH-positive (45%) versus FISH-negative (26%) patients (P = .14), whereas disease control rate (complete response/partial response plus stable disease) was statistically superior (81% v 55%, respectively; P = .02). Patients with FISH-positive tumors had a median progression-free survival time of 6 months compared with 3 months for FISH-negative patients (P = .0008). Median survival time was 15 months for the FISH-positive group compared with 7 months for patients who were FISH negative. (P = .04). Furthermore, survival favored FISH-positive patients receiving concurrent therapy. CONCLUSION: These results are the first to suggest that EGFR FISH is a predictive factor for selection of NSCLC patients for cetuximab plus chemotherapy. Prospective validation of these findings is warranted.

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Cancer Res. 2008 Jul 1;68(13):5040-8.
15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3beta and a tumor suppressor in lung cancer.
Huang G, Eisenberg R, Yan M, Monti S, Lawrence E, Fu P, Walbroehl J, Löwenberg E, Golub T, Merchan J, Tenen DG, Markowitz SD, Halmos B.
Department of Pathology, Division of Hematology/Oncology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio 44106, USA.

The forkhead transcription factor hepatocyte nuclear factor 3beta (HNF3beta) is essential in foregut development and the regulation of lung-specific genes. HNF3beta expression leads to growth arrest and apoptosis in lung cancer cells and HNF3beta is a candidate tumor suppressor in lung cancer. In a transcriptional profiling study using a conditional cell line system, we now identify 15-PGDH as one of the major genes induced by HNF3beta expression. 15-PGDH is a critical metabolic enzyme of proliferative prostaglandins, an antagonist to cyclooxygenase-2 and a tumor suppressor in colon cancer. We confirmed the regulation of 15-PGDH expression by HNF3beta in a number of systems and showed direct binding of HNF3beta to 15-PGDH promoter elements. Western blotting of lung cancer cell lines and immunohistochemical examination of human lung cancer tissues found loss of 15-PGDH expression in approximately 65% of lung cancers. Further studies using in vitro cell-based assays and in vivo xenograft tumorigenesis assays showed a lack of in vitro but significant in vivo tumor suppressor activity of 15-PGDH via an antiangiogenic mechanism analogous to its role in colon cancer. In summary, we identify 15-PGDH as a direct downstream effector of HNF3beta and show that 15-PGDH acts as a tumor suppressor in lung cancer.

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Food Chem Toxicol. 2008 Jul;46(7):2476-84. Epub 2008 Apr 22.
Kotomolide A arrests cell cycle progression and induces apoptosis through the induction of ATM/p53 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells.
Chen CY, Hsu YL, Tsai YC, Kuo PL.
School of Medicine and Health Sciences, Fooyin University, Kaohsiung, Taiwan.

This study first investigates the anticancer effect of kotomolide A (KTA) in human non-small cell lung cancer cells, A549. KTA has exhibited effective cell growth inhibition by inducing cancer cells to undergo G2/M phase arrest and apoptosis. Blockade of cell cycle was associated with increased the activation of ataxia telangiectasia-mutated (ATM). Activation of ATM by KTA phosphorylated p53 at Serine15, resulting in increased stability of p53 by decreasing p53 and murine double minute-2 (MDM2) interaction. In addition, KTA-mediated G2/M phase arrest also was associated with the decrease in the amounts of cyclinB1, cyclinA, Cdc2 and Cdc25C and increase in the phosphorylation of Chk2, Cdc25C and Cdc2. Specific ATM inhibitor, caffeine, significantly decreased KTA-mediated G2/M arrest by inhibiting the phosphorylation of p53 (Serine15) and Chk2. KTA treatment triggered the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl-2 ratios, resulting in mitochondrial membrane potential loss and caspase-9 activation. Taken together, these results suggest a critical role for ATM and p53 in KTA-induced G2/M arrest and apoptosis of human non-small cell lung cancer cells.

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J Clin Oncol. 2008 Jun 10;26(17):2883-9.
Cancer stem cells and the ontogeny of lung cancer.
Peacock CD, Watkins DN.
The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 1550 Orleans St, Rm 546, Baltimore, MD 21231, USA.

Lung cancer is the leading cause of cancer death in the world today and is poised to claim approximately 1 billion lives during the 21st century. A major challenge in treating this and other cancers is the intrinsic resistance to conventional therapies demonstrated by the stem/progenitor cell that is responsible for the sustained growth, survival, and invasion of the tumor. Identifying these stem cells in lung cancer and defining the biologic processes necessary for their existence is paramount in developing new clinical approaches with the goal of preventing disease recurrence. This review summarizes our understanding of the cellular and molecular mechanisms operating within the putative cancer-initiating cell at the core of lung neoplasia.

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Br J Cancer. 2008 Jun 3;98(11):1769-73. Epub 2008 May 27.
Enhancing treatment decision-making: pilot study of a treatment decision aid in stage IV non-small cell lung cancer.
Leighl NB, Shepherd FA, Zawisza D, Burkes RL, Feld R, Waldron J, Sun A, Payne D, Bezjak A, Tattersall MH.
Division of Medical Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario, Canada. Natasha.Leighl@uhn.on.ca

We developed a decision aid (DA) for patients with metastatic non-small cell lung cancer (NSCLC), to better inform patients of their prognosis and treatment options, and facilitate involvement in decision-making. In a pilot study, 20 patients with metastatic NSCLC attending outpatient clinics at a major cancer centre, who had already made a treatment decision, reviewed acceptability of the DA. The median age of the patients was 61 years (range 37-77 years), 35% were male, 20% had a university education, and most (75%) had English as a first language. Most had received chemotherapy, with 65% currently on treatment. Patients were not anxious at baseline and had clear understanding of the goals and toxicity of chemotherapy in advanced NSCLC. After reviewing the DA, patients' anxiety decreased slightly (P=0.04) and knowledge scores improved by 25% (P<0.001). Most improvements in understanding were of prognosis with and without chemotherapy, although patients still believed advanced NSCLC to be curable. Patients rated the DA highly with respect to information clarity, usefulness and were positive about its use in practice, although 40% found the prognostic information slightly upsetting. The DA for advanced NSCLC is feasible, acceptable to patients and improves understanding of advanced NSCLC without increasing patient anxiety.

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Ann Thorac Surg. 2008 Feb;85(2):S785-91.
Stereotactic radiosurgery for thoracic malignancies.
Cesaretti JA, Pennathur A, Rosenstein BS, Swanson SJ, Fernando HC.
Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York 10029, USA. jamie.cesaretti@msnyuhealth.org

Radiosurgery for lung cancer is a novel and promising concept that warrants thorough review. Stereotactic body radiotherapy enables the selective delivery of an intense dose of high-energy radiation to destroy a tumor with precise targeting. The radiobiology and physics behind the use of radiosurgery are presented, followed by a discussion of promising retrospective and prospective clinical data that has been reported from Japan, Europe, and the United States. The article closes with a discussion of multidisciplinary approaches that include radiosurgery which are on the therapeutic horizon.

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Ann Thorac Surg. 2008 Feb;85(2):S780-4.
Radiofrequency ablation to treat non-small cell lung cancer and pulmonary metastases.
Fernando HC.
Department of Cardiothoracic Surgery, Boston Medical Center, Boston University, Boston, Massachusetts 02118, USA. hiran.Fernando@bmc.org

Radiofrequency ablation is being reported with increasing frequency for the treatment of lung tumors. Several studies have demonstrated that this is a feasible and safe approach. Intermediate outcomes are now becoming available. Although tumors up to 5 cm in size can be effectively treated with radiofrequency ablation, results are better for smaller tumors (3 cm or less). This review describes the techniques, available ablation devices, and the potential role of radiofrequency ablation for non-small cell lung cancer (NSCLC) and pulmonary metastases. Resection (lobar or sublobar) should remain the standard therapy for NSCLC. Radiofrequency ablation may be better than conventional external-beam radiation for the treatment of the high-risk individual with NSCLC. Preliminary results for pulmonary metastases are similar to those reported after resection. In addition, patients with pulmonary metastases have been demonstrated to develop recurrences even after thoracotomy and bimanual palpation of the lung. Radiofrequency ablation may be an alternative to resection for the patient with small-diameter pulmonary metastases, and future study of this may be indicated.

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Ann Thorac Surg. 2008 Feb;85(2):S733-6.
Wedge resection and brachytherapy for lung cancer in patients with poor pulmonary function.
McKenna RJ Jr, Mahtabifard A, Yap J, McKenna R 3rd, Fuller C, Merhadi A, Hakimian B.
Department of Thoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. mckennar@cshs.org

BACKGROUND: Although lobectomy is the standard for lung cancer because a wedge resection has a 3 to 5 times greater incidence of local recurrence, poor pulmonary function may preclude lobectomy. For these patients, low-dose-rate brachytherapy has recently been used to decrease local recurrence after sublobar resection. Current techniques expose operating room personnel and patient contacts to unnecessary radioactivity risks. We present our technique of sublobar resection combined with afterload catheters for high-dose-rate brachytherapy for patient benefit with minimal risk to others. METHODS: Forty-eight patients (25 women, 23 men) underwent wedge resection, node dissection, and brachytherapy. A remote-afterloading high-dose-rate unit for radiation produced a median dose of 2450 cGy (350 cGy per fraction over 7 fractions twice daily for 4 days). The dose was prescribed to 1 cm deep to the stapled line. Biologically, this dose is approximately 5000 cGy and above (180 cGy/d eq
uivalent) at the depth of 5 mm in reference to the resection margin. RESULTS: Two patients died. The length of mean stay was 5.5 days (median, 5 days). Complications included prolonged air leak in 5 patients, atrial fibrillation in 5, pneumonia in 3, trapped lung in 2, and 1 each with empyema, bleeding, and recurrent laryngeal nerve injury. Three patients required a blood transfusion. Within the follow-up of 1 to 27 months, there were four recurrences. CONCLUSIONS: Wedge resection and brachytherapy appears to be a reasonable treatment for patients with lung cancer and pulmonary function that prohibits a lobectomy.

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Ann Thorac Surg. 2008 Feb;85(2):S705-9.
Video-assisted thoracoscopic lobectomy: state of the art and future directions.
Shaw JP, Dembitzer FR, Wisnivesky JP, Litle VR, Weiser TS, Yun J, Chin C, Swanson SJ.
Division of Thoracic Surgery, The Mount Sinai Medical Center, New York, New York 10029, USA.

BACKGROUND: Thoracoscopic lobectomy is performed with increasing frequency for early-stage lung cancer. Several published reports suggest thoracoscopic resection is safe, with the potential advantage of shorter hospital stay, quicker recovery, and comparable oncologic results. METHODS: Data on 180 video-assisted thoracoscopic surgery (VATS) patients who underwent thoracoscopic lobectomy or sublobar anatomic resection at our institution between January 2002 and December 2006 were reviewed. The conversion rate to thoracotomy, complications, length of stay, and duration of chest tube drainage were determined. Similar variables were evaluated for patients aged older than 80 years, those with a forced expiratory volume in 1 second (FEV1) that was less than 50% predicted, those who had undergone preoperative neoadjuvant therapy, and those who had undergone lung-sparing anatomic resections. RESULTS: Thoracoscopic anatomic lung resection was performed successfully in 166 patients. One of 180 patients (0.6%) died, and 14 patients (9.2%) underwent conversions. Overall median length of stay was 4 days (range, 1 to 98; interquartile range [IQR], 3), and median duration of chest tube drainage was 3 days (range, 0 to 35 days; IQR, 2). The median length of hospital stay and median chest tube duration for the group aged 80 years and older was 5 and 3 days; for the segmental resection group, 4 and 3 days; for the chemotherapy or radiotherapy induction group, 3.5 and 3 days; and for the FEV1 less than 50% group, 5.5 and 4 days, respectively. No patients died in any of these groups. CONCLUSIONS: Thoracoscopic lung resection can be performed safely in selected patients aged 80 years and older, in those with marginal pulmonary function, and in those with pathologic response to neoadjuvant therapy.

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Semin Oncol Nurs. 2008 Feb;24(1):49-56.
Advances in chemotherapy for non-small cell lung cancer.
Waxman ES.

OBJECTIVES: To discuss the use of chemotherapy and targeted therapy for treating non-small cell lung cancer (NSCLC). DATA SOURCES: Published articles, book chapters, and research papers. CONCLUSION: Chemotherapy has improved both response and survival rates incrementally in patients with advanced NSCLC. Targeted therapy agents are now included in the treatment schema and are impacting overall survival in combination with chemotherapy for first-line therapy and as monotherapy for second- or third-line treatment. In recent years, chemotherapy has also shown efficacy in earlier stages of treatment, especially as adjuvant therapy after surgery. Additionally, elderly patients can tolerate platinum-based chemotherapy without significant toxicities; therefore, age should not be the only determining factor when deciding on treatment for an older person. IMPLICATION FOR NURSING PRACTICE: It is important for nurses to know and understand the background and rationale for many of the cur
rent treatments for NSCLC given today.

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Semin Oncol Nurs. 2008 Feb;24(1):41-8.
Surgical management of non-small cell lung cancer.
Wagner KJ.

OBJECTIVES: To provide an overview of the surgical management of early stage non-small cell lung cancer (NSCLC) and its impact on survival and quality of life. DATA SOURCES: Published articles, book chapters, websites, and research studies. CONCLUSION: The primary treatment choice for early stage NSCLC is surgical resection. Advances have been made in all phases of care from diagnosis to rehabilitation, including better technology for staging, less invasive surgical techniques, and intra-operative and post-operative care that focuses on decreasing complications and improving survival and quality of life. New indications for the addition of adjuvant therapy to surgery can improve disease-free and long-term survival in a disease where the 5-year survival of stage I and II can be less than 50% and overall survival regardless of stage only 15%. IMPLICATIONS FOR NURSING PRACTICE: As health care educators and caregivers, nurses should be informed of the advancements in staging and surgical technique associated with early stage NSCLC and its impact on survival and quality of life.

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Cancer Treat Rev. 2008 Jan 14 [Epub ahead of print]
Particle therapy in lung cancer: Where do we stand?
Pijls-Johannesma M, Grutters JP, Lambin P, Ruysscher DD.
Maastricht Radiation Oncology (MAASTRO clinic), Dr. Tanslaan 12, 6229 ET Maastricht, The Netherlands; GROW, Department of Radiation Oncology, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.

BACKGROUND: From a theoretical point of view, charged particles should lead to superior results compared to photons. In this review, we searched for clinical evidence that protons or C-ions are really beneficial to patients with lung cancer. METHODS: A systematic literature review based on an earlier published comprehensive review was performed and updated until November 1st 2007. RESULTS: Ten fully published series, all dealing with non-small cell lung cancer (NSCLC), mainly stage I, were identified. No phase III trials were found. On proton therapy, 2-5 year local tumor control rates varied between 87% and 57%. The 2 year/5 year overall survival and 2 year/5 year cause specific survival varied between 31-74%/23% and 58-86%/46%, respectively. Late side effects were observed in about 10% of the patients. For C-ion therapy, the local tumor control rate was 77%, while 95% when using a hypofractionated radiation schedule. The 5 year overall survival and cause specific survival rates were 42% and 60%, respectively. Slightly better results were reported when using hypofractionation, 50% and 76%, respectively. The reported late side effects for C-ions were 4%. CONCLUSION: The results with charged particles, at least for stage I disease, seem to be promising. A gain can be expected in reduction of late side effects, especially after treatment with C-ions. Available data demonstrate that particle therapy in general is a safe and feasible treatment modality. Although current results are promising, more evidence is required before particle therapy can become internationally the standard treatment for (subsets of) lung cancer patients.

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Lasers Med Sci. 2008 Jan 23 [Epub ahead of print]
Neodymium:yttrium-aluminium-garnet laser for excision of pulmonary nodules: an institutional review.
Moghissi K, Dixon K.
The Yorkshire Laser Centre, Goole & District Hospital, Woodland Avenue, Goole, East Yorkshire, DN14 6RX, UK, kmoghissi@yorkshirelasercentre.org.

Eighty patients amongst 850 undergoing pulmonary surgery with the use of neodymium:yttrium-aluminium-garnet (Nd:YAG) laser had a solitary pulmonary nodule (</= 50 mm) on chest radiography, which was confirmed or suspected pre-operatively to be primary lung cancer. All patients had a mini-thoracotomy to expose the lesion. They then had Nd:YAG laser to excise the nodule locally. There was no hospital mortality. Six patients had non-fatal post-operative complications. Pathologically, 46 patients had primary lung cancer and ten had secondary lung cancer. Twenty-four others had benign lesions. Mean hospital stay was 5.5 days. Post-operative reduction of forced vital capacity (FVC) and forced expiratory volume in one second (FEV(1)) was 14% and 13% (mean), respectively. Thirty-seven patients with primary lung cancer were followed up for between 12 months and 60 months. Mean survival time of these patients was 39 months (s.d. 13 months). It was concluded that Nd:YAG laser for pulmonary nodular lesions should be considered for a selected group of patients unsuitable for standard resection.

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Anticancer Res. 2007 Nov-Dec;27(6C):4425-9.
Maintenance therapy with gefitinib after first-line chemotherapy in patients affected by advanced non-small cell lung cancer.
Mencoboni M, Bergaglio M, Serra M, Ivaldi GP, Tredici S, Racchi O, Rebella L, Galbusera V, Grosso M, Faravelli B.
Medical Oncology Unit, Villa Scassi Hospital, Genova, Italy. manlio.mencoboni@fastwebnet.it

BACKGROUND: Chemotherapy extends life for patients with advanced non-small cell lung cancer (NSCLC). Second-line treatment of NSCLC includes the use of cytotoxic drugs; however, toxicity is of concern. One molecular target for lung cancer is the epidermal growth factor receptor (EGFR). Gefitinib (Iressa) is an EGFR inhibitor. The aim of our study was to evaluate time to progression (TTP), overall survival (OS) and toxicities in a population affected by NSCLC using Iressa as maintenance therapy after first-line chemotherapy. PATIENTS AND METHODS: Thirty patients were enrolled with stable disease or partial response. Six cycles of a platinum-based first-line chemotherapy were administered. Iressa was administered at the dose of 250 mg/d. RESULTS: Median TTP was 5 months; median overall survival was 8 months. TTP for adenocarcinoma and non-adenocarcinoma patients was 10 months and 3.2 months, respectively. No toxic effects were seen in 80% of the patients; 17% of the patients had grade 1 follicolitis. OS for adenocarcinoma and non-adenocarcinoma patients were 15 and 5.9 months, respectively. CONCLUSION: Gefitinib could be an ideal second-line therapy for adenocarcinoma patients responding to first-line chemotherapy.

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J Clin Oncol. 2007 Oct 22; [Epub ahead of print]
Cancer Care Ontario and American Society of Clinical Oncology Adjuvant Chemotherapy and Adjuvant Radiation Therapy for Stages I-IIIA Resectable Non-Small-Cell Lung Cancer Guideline.
Pister KM, Evans WK, Azzoli CG, Kris MG, Smith CA, Desch CE, Somerfield MR, Brouwers MC, Darling G, Ellis PM, Gaspar LE, Pass HI, Spigel DR, Strawn JR, Ung YC, Shepherd FA. M.D. Anderson.
Cancer Center, Houston, TX; Memorial Sloan-Kettering Cancer Center; New York University School of Medicine, New York, NY; National Comprehensive Cancer Network, Jenkintown, PA; American Society of Clinical Oncology, Alexandria, VA; University of Colorado at Denver Health Sciences Center, Denver, CO; National Cancer Institute Cancer Center, Bethesda, MD; Sarah Cannon Cancer Center, Nashville, TN; Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton; Cancer Care Ontario; Toronto-Sunnybrook Regional Cancer Centre; and the University Health Network, Princess Margaret Hospital, Toronto, Ontario, Canada.

PURPOSE: To determine the role of adjuvant chemotherapy and radiation therapy in patients with completely resected stage IA-IIIA non-small-cell lung cancer (NSCLC). METHODS: The Cancer Care Ontario Program in Evidence-Based Care and the American Society of Clinical Oncology convened a Joint Expert Panel in August 2006 to review the evidence and draft recommendations for these therapies. RESULTS: Available data support the use of adjuvant cisplatin-based chemotherapy in completely resected NSCLC; however, the strength of the data and consequent recommendations vary by disease stage. Adjuvant radiation therapy appears detrimental to survival in stages IB and II, with a possible modest benefit in stage IIIA. CONCLUSION: Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA disease. Although there has been a statistically significant overall survival benefit seen in several randomized clinical trials (RCTs) enrolling a ran
ge of people with completely resected NSCLC, results of subset analyses for patient populations with stage IB disease were not significant, and adjuvant chemotherapy in stage IB disease is not currently recommended for routine use. To date, very few patients with stage IA NSCLC have been enrolled onto RCTs of adjuvant therapy; adjuvant chemotherapy is not recommended in these cases. Evidence from RCTs demonstrates a survival detriment for adjuvant radiotherapy with limited evidence for a reduction in local recurrence. Adjuvant radiation therapy appears detrimental to survival in stage IB and II, and may possibly confer a modest benefit in stage IIIA.

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Radiat Oncol. 2007 Oct 22;2(1):39 [Epub ahead of print]
Radical stereotactic radiosurgery with real-time tumor motion tracking in the treatment of small peripheral lung tumors.
Collins BT, Erickson K, Reichner CA, Collins SP, Gagnon GJ, Dieterich S, McRae DA, Zhang Y, Yousefi S, Levy E, Chang T, Jamis-Dow C, Banovac F, Anderson ED.

ABSTRACT: BACKGROUND: Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors. METHODS: Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3-5) were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45-60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months. RESULTS: Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease. CONCLUSION: Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors.

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Comput Aided Surg. 2007 Sep;12(5):253-61.
Early results of CyberKnife image-guided robotic stereotactic radiosurgery for treatment of lung tumors.
Brown WT, Wu X, Wen BC, Fowler JF, Fayad F, Amendola BE, García S, De La Zerda A, Huang Z, Schwade JG.
CyberKnife Centers of Miami, Miami.

Objective: To determine if image-guided robotic stereotactic radiosurgery (IGR-SRS) by CyberKnife achieves acceptable local control in resectable but medically inoperable patients with non-small cell lung cancer (NSCLC) or pulmonary metastasis, and to evaluate control rates and toxicity. Methods: Treatment details and outcomes were reviewed for 95 patients (age range 33-96 years) with 136 histologically proven cancers treated by IGR-SRS at the CyberKnife Center of Miami between March 2004 and March 2007. Tumor volumes ranged from 1.2 cc to 338 cc. Targeting was accomplished using combined skeletal alignment and real-time tracking via fiducials placed within the tumor. Total doses ranged from 15 to 67.5 Gy delivered in 1 to 5 fractions. Results: Of the 95 patients treated, 78 (82%) are still alive at 1 to 36 months post-treatment. Nineteen patients have died, four from disease other than cancer progression. All patients but one achieved at least partial response to treatment and tolerated radiosurgery well. For the majority of our patients, fatigue had been the main side effect. Conclusions: The delivery of precisely targeted high radiation doses with surgical precision to lung tumors in a hypo-fractionated fashion is feasible and safe. Image-guided robotic stereotactic radiosurgery (IGR-SRS) of lung tumors with the CyberKnife achieves excellent rates of local disease control with limited toxicity to surrounding tissues, and in many cases may be curative for patients for whom surgery is not an option.

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JSLS. 2007 Jul-Sep;11(3):368-74.
Video-Assisted Thoracic Surgery (VATS) Lobectomy: the Evidence Base.
Alam N, Flores RM.
Peter MacCallum Cancer Centre and St. Vincent's Hospital, Melbourne, Australia.

BACKGROUND: Video-assisted thoracic surgery (VATS) lobectomy provides a minimally invasive alternative for management of early stage non-small cell lung cancer, but is still only performed in a few specialized centers around the world. Questions about the safety of the surgery and its adequacy as a cancer operation remain hurdles for many surgeons. METHODS: We performed a systematic review of the literature on VATS lobectomy to assess these questions. The MEDLINE database was queried and the papers analyzed. RESULTS: Four randomized control trials, 11 case-control series, and 10 case series were reviewed. A variety of VATS techniques are used, making generalization of results difficult. The weight of this evidence suggests that VATS lobectomy can be safely performed and is an adequate cancer operation for early stage non-small cell lung cancer. There is also evidence that patients experience less pain with VATS, but that length of hospital stay is similar. CONCLUSION: In expert hands, VATS lobectomy appears to be a safe procedure. However, the published evidence is thin and ongoing study is required, preferably with standardization of VATS techniques.

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Oncologist. 2007;12(10):1205-1214.
Indications and Developments of Video-Assisted Thoracic Surgery in the Treatment of Lung Cancer.
Solli P, Spaggiari L.
University of Milan Faculty of Medicine and Division of Thoracic Surgery, European Institute of Oncology (IEO), Via Ripamonti 435–20141 Milan, Italy. lorenzo.spaggiari@ieo.it.

The term video-assisted thoracic surgery (VATS) is used to describe a modern minimally invasive surgical technique that nowadays represents a valid alternative to open procedures (i.e., thoracotomy) for many chest diseases. The VATS approach is presently used in many intrathoracic disorders, but while well established in benign chest disease, its role continues to evolve regarding the management of lung cancer. It is currently considered for the evaluation and treatment of suspected (or known) pleural effusion and in the diagnosis of indeterminate pulmonary nodules, and it has a complementary role to standard cervical mediastinoscopy in the invasive staging of mediastinal lymph nodes. It has also become an accepted approach for resection of peripheral early-stage lung cancer (stage I) in many centers worldwide and considerable experience has been accumulated in respect to this field, but absolute indications have yet to be firmly defined. This paper reviews indications and current data regarding minimally invasive approaches for the staging and treatment of lung cancer.

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Oncologist. 2007;12(10):1194-1204.
Recent Advances with Topotecan in the Treatment of Lung Cancer.
O'Brien M, Eckardt J, Ramlau R.
FRCP, Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM25JS, United Kingdom. mary.o'brien@rmh.nhs.uk.

Topotecan is a semisynthetic derivative of camptothecin that specifically targets topoisomerase I. It has well-established antineoplastic properties and has been successfully combined with other antineoplastic agents with activity dependent on DNA disruption, such as cisplatin and etoposide. Topotecan is indicated for the treatment of small cell lung cancer (SCLC) sensitive disease after failure of first-line chemotherapy and metastatic ovarian carcinoma after failure of initial or subsequent chemotherapy. Since the approval of topotecan for the second-line treatment of SCLC, studies have been conducted in the first-line setting. Recent studies demonstrate the utility of i.v. topotecan in combination with cisplatin for untreated SCLC. Further, an oral formulation of topotecan is currently under investigation and may provide added convenience for patients. Oral topotecan has been studied in the first- and second-line settings for both SCLC and non-small cell lung cancer (NSCLC). Three recent phase III trials have demonstrated the activity of oral topotecan. In the first study of chemotherapy-naïve patients with extensive-disease SCLC, oral topotecan plus cisplatin provided efficacy and safety similar to those of etoposide plus cisplatin. In a second study of patients with relapsed SCLC, treatment with oral topotecan showed a statistically significant and clinically meaningful longer overall survival time and improvement in dyspnea and quality of life compared with best supportive care alone in all prognostic groups. Finally, in previously treated patients with NSCLC, single-agent oral topotecan was shown to be noninferior in 1-year survival rate relative to the current standard of i.v. docetaxel. In future studies, oral topotecan will represent a good candidate for combination therapy with other i.v. or oral chemotherapy agents, monoclonal antibodies, and small molecule tyrosine kinase inhibitors.

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Oncologist. 2007;12(10):1183-1193.
The Role of Bevacizumab in the Treatment of Non-Small Cell Lung Cancer: Current Indications and Future Developments.
Gridelli C, Maione P, Rossi A, De Marinis F.
Division of Medical Oncology, “S.G. Moscati” Hospital, Contrada Amoretta, 83100 Avellino, Italy. cgridelli@libero.it.

The majority of non-small cell lung cancer (NSCLC) patients present with advanced disease, and despite the improvement in efficacy and safety outcomes with platinum-based chemotherapy, this standard cytotoxic approach has reached a therapeutic plateau, with the prognosis for this clinical condition remaining poor. Advances in the knowledge of tumor biology and mechanisms of oncogenesis have granted the singling out of several molecular targets for NSCLC treatment. Bevacizumab, an anti-growth factor vascular endothelial growth factor (VEGF) monoclonal antibody, is the antiangiogenic agent at the most advanced stage of development in the treatment of solid tumors and also in NSCLC treatment. Bevacizumab, combined with platinum-based chemotherapy, has been demonstrated to improve efficacy outcomes over chemotherapy alone in the treatment of nonsquamous advanced NSCLC in two phase III randomized trials. These represent the first evidence of improvement in treatment outcomes of chemotherapy with targeted therapies in the first-line treatment of advanced NSCLC. Future clinical developments of bevacizumab in NSCLC treatment will include the combination of this agent with other targeted therapies in advanced disease (especially with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor) and the integration of this agent into combined modality approaches for the treatment of early-stage and locally advanced disease.

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Front Radiat Ther Oncol. 2007;40:368-85.
Lung cancer: a model for implementing stereotactic body radiation therapy into practice.
Timmerman R, Abdulrahman R, Kavanagh BD, Meyer JL.
Departments of Radiation Oncology, Dallas, Tex. , USA.

Primary and metastatic tumors to the lung have been principle targets for the noninvasive high-doseper- fraction treatment programs now officially called stereotactic body radiation therapy (SBRT). Highly focused treatment delivery to moving lung targets requires accurate assessment of tumor position throughout the respiratory cycle. Measures to account for this motion, either by tracking (chasing), gating, or inhibition (breath hold and abdominal compression) must be employed in order to avoid large margins of error that would expose uninvolved normal tissues. The treatments use image guidance and related treatment delivery technology for the purpose of escalating the radiation dose to the tumor itself with as little radiation dose to the surrounding normal tissues as possible. Clinical trials have demonstrated superior local control with SBRT as compared with conventionally fractionated radiotherapy. While late toxicity requires further careful assessment, acute and subacute toxicity are remarkably infrequent. Radiographic and local tissue effects consistent with bronchial damage and downstream collapse with fibrosis are common, especially with adequate doses capable of ablating tumor targets. As such, great care must be taken when employing SBRT near the serially functioning central chest structures including the esophagus and major airways. While mechanisms of this injury remain elusive, ongoing prospective trials offer the hope of finding the ideal application for SBRT in treating pulmonary targets.

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J Clin Oncol. 2007 Jul 20;25(21):3124-9.
Results of a Phase II Study of High-Dose Thoracic Radiation Therapy With Concurrent Cisplatin and Etoposide in Limited-Stage Small-Cell Lung Cancer (NCCTG 95-20-53).
Schild SE, Bonner JA, Hillman S, Kozelsky TF, Vigliotti AP, Marks RS, Graham DL, Soori GS, Kugler JW, Tenglin RC, Wender DB, Adjei A.
Mayo Clinic, Department of Radiation Oncology, 13400 E Shea Blvd, Scottsdale, AZ 85259; e-mail: sschild@mayo.edu.

PURPOSE To evaluate the outcome of patients with limited-stage small-cell lung cancer (L-SCLC) treated with cisplatin and etoposide (PE), early prophylactic cranial irradiation (PCI), and high-dose twice-daily thoracic radiotherapy (bid RT). PATIENTS AND METHODS A total of 76 assessable patients were treated on this phase II trial, which included six cycles of PE. PCI (25 Gy/10 fractions) was delivered during cycle 3 to responding patients. Cycles 4 and 5 included concurrent chemotherapy and thoracic RT (30 Gy/20 bid fractions, a 2-week break, and another 30 Gy/20 bid fractions). Results Of the 76 assessable patients, 74 patients (97%) suffered grade 3 or greater (3+) toxicity and 61 patients (80%) had grade 4 or greater (4+) toxicity. Of these adverse events, grade 3+ hematologic toxicity occurred in 72 patients (95%), and grade 3+ nonhematologic toxicity occurred in 55 patients (72%). Only one (2%) of the 61 patients who received PCI experienced treatment failure in the brain. The 5-year survival rate of the 76 assessable patients was 24% (median, 20 months). The 5-year survival rate of the 64 patients who received thoracic RT was 29% (median, 22 months). The 5-year cumulative incidence of in-field treatment failure was 34%. CONCLUSION This regimen included a high total dose of bid TRT, which resulted in a favorable 5-year survival rate. Local failure remains a problem that will require additional investigation. Newer technology should allow the safe administration of greater doses of RT, which should improve patient outcome. Data from eight trials were combined to demonstrate a relationship between RT dose fractionation and 5-year survival.

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Cancer Chemother Pharmacol. 2007 Jul 18; [Epub ahead of print]
Gemcitabine, ifosfamide and paclitaxel in advanced/metastatic non-small cell lung cancer patients: a phase II study.
Piantedosi FV, Caputo F, Mazzarella G, Gilli M, Pontillo A, D'Agostino D, Campbell S, Marsico SA, Bianco A.
Department of Medical-Surgical Oncology and Thoracic Diseases, AORN Monaldi, Via L Bianchi, 80131, Naples, Italy.

Although platinum-based two-drug combinations represent the elective therapeutic approach for advanced/metastatic NSCLC, there is still interest in exploring the efficacy and tolerability of platinum-free combinations including third generation agents in selected NSCLC population. Based on the satisfying activity of gemcitabine (G), ifosfamide (I) and paclitaxel (T) as single agents in NSCLC, we have designed a phase II study to explore an alternative approach to platinum-containing regimens using a combination of these three drugs. To investigate the activity/toxicity of T 175 mg/m(2) on day 1, I 3 g/m(2) on day 1 (with Mesna uroprotection) and G 1,000 mg/m(2) on day 1-8, every 3 weeks in the treatment of advanced/metastatic NSCLC, 46 patients (38 male, 8 female) with NSCLC were enrolled: mean age 58 (range 33-70); Stage IIIB/IV = 15/31; ECOG PS 0-1/2 = 31/15; Histology: adenocarcinoma = 20, squamous = 14, large cell = 3, NSCLC = 8, adenosquamous = 1. A total of 221 cycles have been administered (median number 4.8 for patients). In intent-to-treat analysis, partial response was achieved in 17 patients (36.95%), stable disease and progressive disease was detected in 16 (34.78%) and 10 (21.73%) patients, respectively. Time to progression was 30.9 weeks; median survival time was 42.7 weeks; the survival rates at 12 and 18 months were 34.79 and 15.21%, respectively. No toxic deaths occurred. No patients experienced grade 4 neutropenia and thrombocytopenia. Neutropenia grade 3 occurred in 10 patients (21.7%); Anemia grade 3 in 1 (2.1%); Thrombocytopenia grade 2 in two patients (4.3%) and grade 3 in one (2.1%). Peripheral neuropathy grade 1 occurred in ten (21.7%) and grade 2 in two patients (4.3%). Additional non-haematological toxicities were mild nausea, emesis and fatigue. GIT is well tolerated and active regimen in both advanced and metastatic NSCLC. These data suggest future investigations for GIT schedule as a possible alternative to platinum-based regimens in selected advanced/metastatic NSCLC patients where survival, tolerability and quality of life are the primary goals.

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Cochrane Database Syst Rev. 2007 Jul 18;3:CD006157.
Chemotherapy and surgery versus surgery alone in non-small cell lung cancer.
Burdett S, Stewart L, Rydzewska L.

BACKGROUND: The role of pre-operative chemotherapy in the treatment of patients with non-small cell lung cancer (NSCLC) was not clear. A systematic review and quantitative meta-analysis were therefore undertaken to evaluate the available evidence from randomised trials. OBJECTIVES: To evaluate the effect of pre-operative chemotherapy on survival in patients with non-small cell lung cancer. If adequate data are available, to investigate whether or not pre-defined patient subgroups benefit more or less from pre-operative chemotherapy. SEARCH STRATEGY: MEDLINE and CANCERLIT searches for randomised controlled trials (RCTs) were supplemented by information from trial registers and by handsearching relevant meeting proceedings and by discussion with relevant trialists and organisations. SELECTION CRITERIA: RCTs were eligible for inclusion provided the patients had been randomised between chemotherapy followed by surgery versus surgery alone and that the method of randomisation precluded prior knowledge of the treatment to be assigned. DATA COLLECTION AND ANALYSIS: A systematic review and meta-analysis based on aggregate data extracted from trial publications was carried out to assess the effectiveness of pre-operative chemotherapy in NSCLC. This involved identifying eligible RCTs and extracting aggregate data from the abstracts or reports of these RCTs. Hazard ratios were calculated from published summary statistics and then combined to give pooled estimates of treatment efficacy. MAIN RESULTS: Twelve eligible RCTs were identified. Data were available from seven RCTs including 988 patients (75% of eligible patients). Pre-operative chemotherapy increased survival with a hazard ratio of 0.82 (95%CI 0.69-0.97) P = 0.022. This is equivalent to an absolute benefit of 6%, increasing overall survival across all stages of disease from 14% to 20% at 5 years. There was no evidence of statistical heterogeneity (P = 0.980, I(2 )= 0). AUTHORS' CONCLUSIONS: This analysis shows a significant increase in survival attributable to pre-operative chemotherapy. This is currently the best estimate of the effectiveness of this therapy, but is based on a small number of trials and patients. This analysis was unable to address important questions such as whether particular types of patients may benefit more or less from pre-operative chemotherapy or whether the early stopping of a number of included RCTs impacted on the results. These issues may be addressed by an ongoing individual patient data (IPD) meta-analysis.

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Chirurg. 2007 Jul 20; [Epub ahead of print]
[Solitary pulmonary nodule : Assessment and therapy.]
[Article in German]
Bergmann T, Bölükbas S, Beqiri S, Trainer S, Schirren J.
Klinik für Thoraxchirurgie, HSK, Dr-Horst-Schmidt-Kliniken, Ludwig-Erhardt-Straße 100, 65199, Wiesbaden, Deutschland, thomas.bergmann@hsk-wiesbaden.de.

Solitary pulmonary nodules (SPN) are radiologically defined as intraparenchymal lung lesions not bigger then 3 cm. In general all pulmonary nodules should be considered malignant until proven otherwise. Primary peripheral lung cancer is the most common cause, at 40%. The probability that an SPN is malignant increases with patient age. Spiral chest CT is the ideal imaging to indicate the precise anatomical location and expose other pathological findings. Malignant SPN can also persist without change for over 2 years. Only complete histological examination can exclude malignance. Therefore every SPN should be resected in operable patients. The surgical risk of video-assisted pulmonary resection and diagnostic thoracotomy is low. For patients who are not operable, other diagnostic procedures such as transthoracic needle aspiration or positron emission tomography may be helpful.

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Curr Treat Options Oncol. 2007 Jun 7; [Epub ahead of print]
Optimal Duration of Chemotherapy in Advanced Non-Small Cell Lung Cancer.
Lustberg MB, Edelman MJ.
University of Maryland Marlene and Stewart Greenebaum Cancer Center, Rm N9E08, 22 S. Greene Street, Baltimore, MD, 21201, USA, medelman@umm.edu.

OPINION STATEMENT: NSCLC is the leading cause of cancer mortality in the United States. Approximately 30-40% of patients present with advanced stage disease (Stage IIIb with malignant effusion and Stage IV) and the majority of those who present with "earlier" disease will ultimately develop and succumb to metastatic lung cancer. Although platinum-based combination chemotherapy has been shown to impact overall survival and quality of life, it is not curative and less than 25% of patients survive 2 years. Therefore, the benefits of chemotherapy must be weighed against toxicity, inconvenience, and cost. Several randomized trials have shown that there is no added benefit of extending first line, platinum-based chemotherapy beyond four cycles. There was no additional survival benefit and patients experienced increased toxicity with longer durations of therapy. Attempts to improve outcome by planned sequential therapy, i.e. shifting from one cytotoxic regimen to another after a fixed number of cycles have also not been successful. Several new so-called "targeted" therapeutic agents have recently been evaluated in clinical trials to assess whether the efficacy of first line chemotherapy with platinum doublets can be improved with the addition of these agents. These include bevacizumab, epidermal growth factor receptor inhibitors (erlotinib and gefitinib), bexarotene, matrix metalloproteinase inhibitors, and others. Other than bevacizumab, none have demonstrated benefit in this scenario. The design of most of these trials employed the concurrent use of the new agent with six cycles of platinum-based chemotherapy (usually either carboplatin/paclitaxel or cisplatin/gemcitabine) and then continued the new agent until relapse. Three agents have demonstrated benefit in randomized studies in the second line setting, docetaxel, pemetrexed, and erlotinib. No study has evaluated the optimal duration of therapy for these agents, though for erlotinib, it appears that use until progression is optimal. Future studies of novel agents will need to explore not only the potential use of these agents in combination or in comparison with standard therapy, but also the duration of therapy and consider issues of survival, quality of life, and cost.

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Curr Treat Options Oncol. 2007 Jun 19; [Epub ahead of print]
Management of Locally Advanced Non Small Cell Lung Cancer from a Surgical Perspective.
Roy MS, Donington JS.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

OPINION STATEMENT: Stage III, locally advanced NSCLC, represents an incredibly heterogeneous group of patients. Optimal therapy for this group is controversial and the role of surgery is not clearly defined. There have been several randomized trials over the past three decades that have helped to guide our decision-making. In patients with T3N1 tumors, surgery is the primary treatment and there is now evidence for the use of adjuvant chemotherapy. Consensus has shown that the majority of IIIB tumors are not amenable to resection. Exceptions to this are selective T4 tumors by virtue of a satellite nodule or those with isolated invasion of the spine, superior sulcus, carina or vena cava. Such tumors require technically difficult resections and are reserved for patients with excellent performance status and no evidence of N2 disease. Patients with N2 disease represent the largest proportion of patients with stage III disease. There is an increasing understanding of the importance of multi-modality therapy for N2 disease, but the exact role and timing of chemotherapy, radiation and surgery remains unclear. The role of surgery is determined by the bulk of the mediastinal node involvement. Clearly, not all N2 disease is the same. Patients with micometastatic disease and single station nodal involvement have the greatest chance for cure and surgery has a significant role in their treatment. In addition, the ability to sterilize mediastinal lymph nodes with induction therapy correlates strongly with survival. However, the ideal form and timing of induction therapy has yet to be determined. Bulky multi-station disease is frequently not amenable to surgery and is best approached with definitive chemotherapy and radiation.

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Curr Opin Oncol. 2007 Mar;19(2):98-102.
Combined targeted therapies in non-small cell lung cancer: a winner strategy?
Cascone T, Gridelli C, Ciardiello F.
aCattedra di Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale 'F Magrassi e A Lanzara', Seconda Universita degli Studi di Napoli, Naples bDivisione di Oncologia Medica, Ospedale 'S G Moscati', Avellino, Italy.

PURPOSE OF REVIEW: Current treatment modalities provide limited improvement in the natural course of lung cancer, and prognosis remains poor. Lung cancer is a malignancy with great molecular heterogeneity. The complexity of the signalling process leading to cancer cell proliferation and to the neoplastic phenotype supports the necessity of interfering at different stages to avoid cancer cell resistance to therapy. RECENT FINDINGS: Use of several agents with multiple growth factor receptor or intracellular targets has shown encouraging results in phase I and II clinical trials in non-small cell lung cancer. ZD6474 is a dual epidermal growth factor receptor and vascular endothelial growth factor receptor 2 small-molecule tyrosine kinase inhibitor; sorafenib is an oral kinase inhibitor of Raf-1 and is also active against vascular endothelial growth factor receptors 2 and 3, platelet-derived growth factor receptor beta, and c-KIT. Sunitinib is a vascular endothelial growth factor receptor 1, 2, and 3, c-KIT, and platelet-derived growth factor receptor alpha and beta tyrosine kinase inhibitor. SUMMARY: Combined use of epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib and the humanized vascular endothelial growth factor receptor monoclonal antibody bevacizumab in advanced, chemotherapy-refractory non-small cell lung cancer has shown promising results.

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Curr Opin Oncol. 2007 Mar;19(2):92-7.
Neoadjuvant chemotherapy in the treatment of nonsmall-cell lung cancer.
De Pauw R, van Meerbeeck JP.
Department of Thoracic Oncology, University Hospital Ghent, Belgium.

PURPOSE OF REVIEW: To review the recent evidence regarding the potential benefit on the outcome of neoadjuvant chemotherapy in patients with early-stage nonsmall-cell lung cancer and compare this evidence with the theoretical advantages and disadvantages of the approach. RECENT FINDINGS: The available evidence has mostly not yet been published in full manuscript form and should be interpreted cautiously. The observed gain in survival with neoadjuvant treatment is not consistent with expectations. Literature-based meta-analyses, however, estimate a gain in survival of at least 6% after 5 years. Neoadjuvant chemotherapy results in clinical downstaging in approximately 40-60% of the patients and pathological complete response rate in 5-10%. Neoadjuvant chemotherapy does not reduce the number of pneumonectomies. As expected, its compliance is better compared with adjuvant treatment. Neoadjuvant chemotherapy does not delay surgery or result in an increased hospital stay or rate of perioperative complications, when compared with immediate surgery. Neoadjuvant regimens should be platinum-based and at least three cycles of chemotherapy should be administered. SUMMARY: Neoadjuvant chemotherapy in early-stage nonsmall-cell lung cancer should not yet be offered outside of clinical trials and will in the future have to be compared with adjuvant chemotherapy.

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Curr Opin Oncol. 2007 Mar;19(2):84-91.
Surgery of non-small cell lung cancer in the elderly.
Spaggiari L, Scanagatta P.
aDivision of Thoracic Surgery, European Institute of Oncology bUniversity of Milan, School of Medicine, Milan, Italy.

PURPOSE OF REVIEW: The aim of this review is to analyze recent evidence for optimal treatment of elderly patients with non-small cell lung cancer, focusing on surgery, and possibly to foresee the future strategies to apply in these patients. RECENT FINDINGS: Surgery in elderly patients affected by non-small cell lung cancer is safe and feasible when careful preoperative respiratory and cardiac studies have been carried out and the disease has been properly staged. The surgical treatment is not to be denied in elderly patients due to age per se, but when a major contraindication to surgery has been recognized. Long term survival for elderly patients with early stage lung cancer treated by anatomical pulmonary resection is comparable to the survival rate of younger patients. Pneumonectomy, extended surgical procedure or preoperative induction chemotherapy are major risk factors for an increased postoperative morbidity and mortality rate. When co-morbidities are present or a patient is 80 years or older, there is evidence that a non-anatomical resection can be performed without affecting long-term results. SUMMARY: Due to the aging of the general population, elderly patients will become a large percentage of the cases of non-small cell lung cancer to be treated. Implementing preoperative cardiologic studies and redefining selective respiratory criteria specifically could dramatically improve results.

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Anticancer Drugs. 2007 Mar;18(3):255-61.
Treatment options for relapsed small-cell lung cancer.
Azim HA Jr, Ganti AK.
aDepartment of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt bDepartment of Internal Medicine, University of Nebraska Medical Center cDepartment of Internal Medicine, Omaha VA Medical Center, Omaha, Nebraska, USA.

Small-cell lung cancer is a chemo-sensitive disease with a response rate ranging from 70 to 90% for first-line treatment; however, relapses are very common and as a result long-term survival is poor. Chemotherapy has demonstrated a benefit over the best supportive care, even in patients who have relapsed after initial treatment with a platinum-based regimen. Agents currently being used in salvage therapy include topotecan, cyclophosphamide, doxorubicin and vincristine regimen. In the last 5 years, several drugs have shown promise in initial evaluation; however, randomized phase III trials would be needed to answer this question. Our understanding of the biology of small-cell lung cancer has improved dramatically over the past few years and this has translated into the developments of new therapeutic targets for this disease. Agents affecting several targets, including bcl-2, matrix metalloproteinases, epidermal growth factors and angiogenesis, are being studied currently and have the potential to change the treatment paradigms of this otherwise fatal malignancy. This review focuses on the various current and future options, including cytoxic and targeted agents, for salvage therapy in patients with this disease.

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J Clin Oncol. 2007 Feb 1;25(4):418-23.
Randomized phase II trial of paclitaxel plus carboplatin or gemcitabine plus cisplatin in Eastern Cooperative Oncology Group performance status 2 Non-small-cell lung cancer patients: ECOG 1599.
Langer C, Li S, Schiller J, Tester W, Rapoport BL, Johnson DH; Eastern Cooperative Oncology Group.
Thoracic Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. cj_langer@fccc.edu

PURPOSE: Appropriate therapy for Eastern Cooperative Oncology Group (ECOG) performance status (PS) -2 patients with advanced non-small-cell lung cancer (NSCLC) remains challenging. PS-2 patients on ECOG 1594 had a median survival (MS) of only 4.1 months and 1-year overall survival (OS) of 19%. Three percent had grade 5 toxicity. PATIENTS AND METHODS: ECOG 1599, the first PS 2-specific, US cooperative group trial for treatment-naive advanced NSCLC, randomly assigned patients to dose-attenuated carboplatin/paclitaxel (the least toxic regimen in ECOG 1594) or gemcitabine/cisplatin (which yielded an MS of 7.9 months in PS-2 patients). Patients received either carboplatin (area under the concentration-time curve, 6) and paclitaxel 200 mg/m2 every 3 weeks (CbP) or gemcitabine 1 g/m2 days 1 and 8 and cisplatin 60 mg/m2 day 1 every 3 weeks (CG). RESULTS: One hundred three patients were enrolled; 100 proved eligible. Median age was 66 years; 46% had at least 5% weight loss; 88% had stage IV or recurrent disease. Median number of cycles administered was three per arm. CbP featured more grade 3 neutropathy (10% v 0%) and more grade > or = 3 neutropenia (59% v 33%), whereas CG yielded more grade 3 thrombocytopenia (33% v 14%), more grade 3 fatigue (22% v 14%), and more grade > or = 1 creatinine elevations (43% v 6%). One grade 5 toxicity, confined to the CbP arm, occurred. Response rate, time to progression, MS, and 1-year OS rates for CG and CbP, were 23%, 4.8 months, 6.9 months, and 25%, and 14%, 4.2 months, 6.2 months, and 19%, respectively. CONCLUSION: Platinum-based combination chemotherapy for PS-2 patients with NSCLC is feasible with acceptable toxicity, but survival in these patients remains inferior to that of PS-0 to -1 patients.

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Ann Thorac Surg. 2007 Feb;83(2):425-31; discussion 432.
Morbidity of lung resection after prior lobectomy: results from the Veterans Affairs National Surgical Quality Improvement Program.
Linden PA, Yeap BY, Chang MY, Henderson WG, Jaklitsch MT, Khuri S, Sugarbaker DJ, Bueno R.
Division of Thoracic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. plinden@partners.org

BACKGROUND: Lobectomy is the current standard operation for localized lung cancer. Patients who undergo lobectomy have a 1% to 2% chance per year of developing a second lung cancer. The risks of repeat lung resection have not been well quantified or analyzed. We used a national, prospectively recorded database to evaluate the complication rate and risk factors in this population. METHODS: The Veterans Affairs National Surgical Quality Improvement Program Database was queried for all patients who underwent lobectomy, followed by an additional lung resection, between 1994 and 2002. Preoperative variables, intraoperative variables, and complications were analyzed. Pulmonary function data were not collected. RESULTS: Excluding 17 patients who underwent repeat resection for complications of lobectomy, 186 patients underwent 191 repeat resections. The 30-day mortality was 11%; the complication rate was 19%. Mortality for pneumonectomy was 34%, lobectomy, 7%; segmentectomy, 0%; and wedge resection, 6%. The most frequent complications were pneumonia (9%), reintubation (8%), ventilator dependence (6%), cardiac arrest (3%), dysrhythmia (3%), and sepsis (3%). Multivariate analysis revealed that operative time exceeding 2 hours, preoperative dyspnea at rest or with minimal exertion, and white blood cell count of more than 10,000/mm3 were predictors of complication. Presence of a contaminated/infected case, pneumonectomy, and intraoperative transfusion were predictors of death. Age, complications from prior lobectomy, time interval between lobectomy and repeat resection, smoking history, other comorbidities, and preoperative laboratory values were not independent predictors. CONCLUSIONS: Repeat lung resection after lobectomy carries an 11% overall mortality predicted by the presence of a contaminated/infected case, need for intraoperative transfusion, and pneumonectomy versus a lesser resection.

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Ann Thorac Surg. 2007 Feb;83(2):409-17; discussioin 417-8.
Survival after recurrent nonsmall-cell lung cancer after complete pulmonary resection.
Sugimura H, Nichols FC, Yang P, Allen MS, Cassivi SD, Deschamps C, Williams BA, Pairolero PC.
Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

BACKGROUND: Survival characteristics of patients who have recurrent nonsmall-cell lung cancer after surgical resection are not well understood. Little objective evidence exists to justify treatment for these patients. METHODS: We prospectively followed 1,361 consecutive patients with nonsmall-cell lung cancer who underwent complete surgical resection at our institution from January 1997 to December 2001. Only patients having recurrent cancer were included in the analysis. Multivariable Cox proportional hazards models were used to evaluate the effect of prognostic factors on postrecurrence survival. RESULTS: Follow-up was achieved in 1,073 patients, and recurrent cancer developed in 445. Complete information was available on 390 patients for analysis. There were 262 men and 128 women. Median age at time of recurrence was 69 years. Median time from surgical resection to recurrence was 11.5 months, and median postrecurrence survival was 8.1 months. Recurrence was intrathoracic in 171 patients, extrathoracic in 172, and a combination of both in 47. Treatments after recurrence included surgery in 43 patients, chemotherapy in 59, radiation in 73, and a combination in 96. All patients who received treatment survived longer than those who received no treatment. Preoperative chemotherapy and postoperative radiotherapy for the primary lung cancer, poor Eastern Cooperative Oncology Group Performance Status, decreased disease-free interval from initial resection to recurrence, symptoms at recurrence, and certain location of recurrence significantly decreased postrecurrence survival. CONCLUSIONS: In our experience, treatment for recurrent nonsmall-cell lung cancer significantly prolongs survival. Various treatment modalities including surgery should be considered in patients with postoperative recurrent nonsmall-cell lung cancer.

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J Support Oncol. 2007 Jan;5(1):19-24.
Role of chemotherapy for palliation in the lung cancer patient.
Stinnett S, Williams L, Johnson DH.
Division of Hematology & Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

Lung cancer is the leading cause of cancer-related deaths in the United States and presents with a constellation of common, often persistent, and severe symptoms. Chemotherapy is well known to impart a survival benefit; however, the benefit of chemotherapy for relief of lung cancer symptoms has been slow to gain recognition. Tumor-related symptoms such as pain, cough, and dyspnea are improved, along with constitutional symptoms such as fatigue and overall quality of life, sometimes even after failure of previous regimens. The efficacy of chemotherapy for the relief of symptoms and improvement in quality of life makes these drugs a fundamental part of palliative care.

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Clin Cancer Res. 2007 Jan 15;13(2):515-22.
A phase I study of pemetrexed, Carboplatin, and concurrent radiotherapy in patients with locally advanced or metastatic non-small cell lung or esophageal cancer.
Seiwert TY, Connell PP, Mauer AM, Hoffman PC, George CM, Szeto L, Salgia R, Posther KE, Nguyen B, Haraf DJ, Vokes EE.
Authors' Affiliations: Section of Hematology/Oncology, Department of Medicine.

PURPOSE: The primary objective of this phase I study was to determine the maximum tolerated dose for pemetrexed, alone and in combination with carboplatin, with concurrent radiotherapy. EXPERIMENTAL DESIGN: Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) or esophageal cancer were treated every 21 days for two cycles. Regimen 1 was pemetrexed (200-600 mg/m(2)); regimen 2 was pemetrexed (500 mg/m(2)) with escalating carboplatin doses (AUC = 4-6). Both regimens included concurrent radiation (40-66 Gy; palliative-intent doses were lower). RESULTS: Thirty patients (18 locally advanced and 12 metastatic with dominant local symptoms) were enrolled, with an Eastern Cooperative Oncology Group performance status of 0/1/2 (n = 8/21/1). All dose levels were tolerable for regimen 1 (n = 18: 15 NSCLC and 3 esophageal cancers) and regimen 2 (n = 12: all NSCLC). In regimen 1, one dose-limiting toxicity (grade 4 esophagitis/anorexia) occurred (500 mg/m(2)). Grade 3 neutropenia (3 of 18 patients) was the main hematologic toxicity. In regimen 2, one dose-limiting toxicity (grade 3 esophagitis) occurred (500 mg/m(2); AUC = 6); grade 3/4 leukopenia (4 of 12 patients) was the main hematologic toxicity. Four complete responses (2 pathology proven) and eight partial responses were observed. When systemically active chemotherapy doses were reached, further dose escalation was discontinued, and a phase II dose-range was established (pemetrexed 500 mg/m(2) and carboplatin AUC = 5-6). CONCLUSIONS: The combination of pemetrexed (500 mg/m(2)) and carboplatin (AUC = 5 or 6) with concurrent radiation is well tolerated, allows for the administration of systemically active chemotherapy doses, and shows signs of activity. To further determine efficacy, safety profile, and optimal dosing, the Cancer and Leukemia Group B study 30407 is currently evaluating this regimen in patients with unresectable stage III NSCLC
  
Previous Lung Cancer Research: 2002-2006   
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