OBJECTIVE: Determine the safety and efficacy of cetuximab plus paclitaxel and carboplatin as initial treatment of stage III/IV ovarian cancer. METHODS: An initial intravenous [IV] dose of cetuximab (400 mg/m(2)) was administered over 120 min followed by weekly IV infusions of cetuximab (250 mg/m(2)) administered over 60 min. Paclitaxel (175 mg/m(2)) and carboplatin (area under the curve [AUC] of 6) were administered IV every 21 days for 6 cycles. The order of administration was cetuximab followed by paclitaxel and then carboplatin. Patients achieving a clinical complete response after 6 cycles were eligible to continue weekly cetuximab for 6 months or until toxicity or disease progression. Safety was evaluated using NCI Common Toxicity Criteria version 2.0. Progression-free survival (PFS) at 18 months was determined and compared with historical controls. RESULTS: Forty-one patients were enrolled in this study; 40 received treatment and were evaluable for toxicity, and 38 were evaluable for PFS. Grade 3/4 treatment-related toxicities included febrile neutropenia (12.5%), rash (2.5%), hypersensitivity reaction (7.5%), and hypomagnesemia (12.5%). Common grade 1/2 toxicities attributed to cetuximab included acneiform rash (82.5%), hirsutism (7.5%) or abnormal hair growth (25%), and nail disorders (22.5%), which in 3 cases resulted in the patient's discontinuation from the study. Median PFS was 14.4 months, and PFS at 18 months was 38.8%. CONCLUSIONS: The combination of cetuximab with paclitaxel and carboplatin is adequately tolerated as primary therapy for ovarian cancer but did not demonstrate prolongation of PFS when compared to historical data.