On July 14, 2006, FDA approved gemcitabine (Gemzar, Eli Lilly and Company) in combination with carboplatin for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum based therapy.
The approval was based on a single multicenter, international, open-label, randomized trial enrolling 356 ovarian cancer patients whose disease had relapsed at least 6 months after first-line platinum-based therapy. Patients were randomized to receive either gemcitabine 1000 mg/m2 on days 1 and 8 of a 21 day cycle plus carboplatin (AUC 4) administered on day 1 of each cycle (GC) or to receive carboplatin (AUC 5) administered on day 1 of each 21 day cycle (C).
One hundred seventy-eight patients received GC and 178 patients received C. Patients were comparable for age, baseline ECOG performance status, platinum-free interval, and first-line therapy regimen.
GC treatment resulted in a significant improvement in progression-free survival (PFS). Median PFS was 8.6 months for GC-treated patients and 5.8 months for C-treated patients [log rank p=0.0038; hazard ratio 0.72 (95%, C.I. 0.57, 0.90)]. A significant improvement in the investigator-assessed overall response rate was demonstrated for the addition of gemcitabine to carboplatin (47% versus 31%, p=0.0016), but not in the independently reviewed response rate that excluded sonography or physical exam findings (46% versus 36%, p=0.11).
Approximately 75% of patients in each arm received post-study chemotherapy, including 13 of 120 patients on the C treatment arm for whom post-progression chemotherapy drugs were known and who received gemcitabine after progression. No significant difference in overall survival was observed. The median survival was 18.0 months for GC-treated patients compared to 17.3 months for those receiving single-agent carboplatin [p=0.8977, hazard ratio 0.98 (95% C.I. 0.78, 1.24)].
Hematologic toxicity was the most frequent adverse event. Grade 4 (CTC) neutropenia, anemia and thrombocytopenia occurred in 29%, 6% and 5%, respectively, of patients receiving GC compared to 1%, 2%, and 1% of those receiving single-agent carboplatin. Red blood cell and platelet transfusions were more common in GC-treated patients. Grade 3 neurosensory toxicity was observed in 1% receiving GC and 2% of C-treated patients.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available in Drugs@FDA
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