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 therefore important to develop new non-cross-resistant drugs. Gemcitabine (2',2'-difluorodeoxycytidine) has shown a broad spectrum of antineoplastic activity in tumor cell cultures in vitro and in animal tumor models. 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 further characterize the toxicity of the compound.
METHODS: Gemcitabine (800 mg/m2) was given intravenously once a week for 3 consecutive weeks, followed by 1 week of rest. A maximum of two different prior treatment regimens was allowed. Response was assessed by pelvic examination and/or ultrasound and computed tomography scans every other course.
RESULTS: Fifty patients were eligible; 35 (70%) had bulky disease (tumor greater than 5 cm in diameter). All patients had received prior platinum-containing combination chemotherapy. Forty-two patients were assessable for response. Eight (19%) of the 42 patients (95% confidence interval = 9%-34%) achieved a partial response, with a median response duration of 8.1 months (range, 4.4-12.5 months). All responders started treatment with gemcitabine within 6 months of prior treatment, and seven of the eight responders were resistant to first-line platinum-containing combination chemotherapy. Overall median time to progression was 2.8 months (range, 0.2 12.5 months), and overall median survival was 6.2 months (range, 0.2-26.0 months). Forty-eight patients were assessable for toxicity. Leukocytopenia and thrombocytopenia were the main toxic effects that caused dose omissions (27% and 14%, respectively) and dose reductions (37% and 21%, respectively). A transient mild flu-like syndrome occurred in 28% of the patients, and treatment-related peripheral edema developed in 22%. Grade 1 hematuria (53% of patients), grade 1-2 proteinuria (79% of patients), and liver toxicity that was mostly grade 1-2 (59% of patients) were also observed.
CONCLUSIONS: Gemcitabine is a well-tolerated new drug with activity in platinum-resistant ovarian cancer patients. IMPLICATIONS: Confirmatory trials are needed, and the activity of gemcitabine in previously untreated patients should be assessed.