Second-line carboplatin and gemcitabine in platinum sensitive ovarian cancer--a dose-finding study by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Ovarian Cancer Study Group.

BACKGROUND: Despite the progress that has been achieved in the last years, recurrence rates in ovarian cancer patients are still considerably high and the majority of patients ultimately become candidates for second-line treatment. Carboplatin reinduction is a broadly adopted regimen in patients with recurrences occurring six months or later after first-line treatment. Gemcitabine is among the candidates as combination partner in second-line regimens.

PATIENTS AND METHODS: We performed a study with escalating doses of gemcitabine combined with carboplatin in 26 platinum-pretreated patients with recurrent ovarian cancer and a treatment-free interval of 6+ months. Dose-limiting toxicity (DLT) and a maximum tolerable dose (MTD) recommendable for further trials was evaluated.

RESULTS: The DLT was myelosuppression, mainly thrombocytopenia. No dose limiting non-hematological toxicities were observed. The MTD of gemcitabine was 1,000 mg/m2 given on days 1 + 8 of a three-week schedule combined with carboplatin AUC 4 given on day 1. The majority of evaluable patients showed an objective response (62.5%), and median progression-free and overall survival were 10 and 18+ months, respectively.

CONCLUSION: Gemcitabine-carboplatin given according to the MTD is well tolerated and active against recurrent platinum-sensitive disease. A randomized trial comparing carboplatin with or without gemcitabine in platinum-sensitive ovarian cancer has already been initiated.