PHASE-II STUDY OF GEMCITABINE (2',2'-DIFLUORODEOXYCYTIDINE) IN PREVIOUSLY TREATED OVARIAN-CANCER PATIENTS

Background: Platinum-containing combination chemotherapy has resulted in improved survival rates in patients with advanced ovarian carcinoma , but the majority of the patients still die of their disease. It is t herefore important to develop new non-cross-resistant drugs. Gemcitabi ne (2',2'-difluorodeoxycytidine) has shown a broad spectrum of antineo plastic activity in tumor cell cultures in vitro and in animal tumor m odels. Clinical activity also has been reported in a variety of solid tumor types. Purpose: Our purpose was to assess the clinical activity of gemcitabine in previously treated ovarian cancer patients and to fu rther characterize the toxicity of the compound. Methods: Gemcitabine (800 mg/m(2)) was given intravenously once a week for 3 consecutive we eks, followed by 1 week of rest. A maximum of two different prior trea tment regimens was allowed. Response was assessed by pelvic examinatio n and/or ultrasound and computed tomography scans every other course. Results: Fifty patients were eligible; 35 (70%) had bulky disease (tum or greater than 5 cm in diameter). All patients had received prior pla tinum-containing combination chemotherapy. Forty-two patients were ass essable for response. Eight (19%) of the 42 patients (95% confidence i nterval = 9%-34%) achieved a partial response, with a median response duration of 8.1 months (range, 4.4-12.5 months). All responders starte d treatment with gemcitabine within 6 months of prior treatment, and s even of the eight responders were resistant to first-line platinum-con taining combination chemotherapy. Overall median time to progression w as 2.8 months (range, 0.2-12.5 months), and overall median survival wa s 6.2 months (range, 0.2-26.0 months). Forty-eight patients were asses sable for toxicity. Leukocytopenia and thrombocytopenia were the main toxic effects that caused dose omissions (27% and 14%, respectively) a nd dose reductions (37% and 21%, respectively). A transient mild flu-l ike syndrome occurred in 28% of the patients, and treatment-related pe ripheral edema developed in 22%. Grade 1 hematuria (53% of patients), grade 1-2 proteinuria (79% of patients), and liver toxicity that was m ostly grade 1-2 (59% of patients) were also observed. Conclusions: Gem citabine is a well-tolerated new drug with activity in platinum-resist ant ovarian cancer patients. Implications: Confirmatory trials are nee ded, and the activity of gemcitabine in previously untreated patients should be assessed.