Phase I/II trial of combination topotecan and vinorelbine in patients with refractory gynecologic cancer.
5152 Background: Topotecan (T) and vinorelbine (V) have shown efficacy in recurrent ovarian and cervical cancer. The purpose of this trial was to determine the recommended dose of combination T and V and to assess its efficacy in patients with refractory gynecologic cancer. METHODS: Sixteen patients with measurable disease and advanced gynecologic malignancies were enrolled. The phase I study evaluated the toxicity of combining T (0.75-1.25 mg/m2) administered as a 30 minute infusion on days 1,2, and 3 and V (20-22.5 mg/m2) IVP on days 1 and 8 of a 21 day cycle. The phase II study evaluated 8 patients treated with T (0.75 mg/m2) on days 1,2, and 3 followed by V(20 mg/m2) IVP on days 1 and 8. RESULTS: Five DLTs appeared during the first 8 cycles in levels 1 and 2. The MTD was reached and the recommended dose for this combination schedule was T: 0.75 mg/m2 on days #1, 2, and 3 combined with V: 22.5 mg/m2 on days # 1 and 8. Phase II: 8 patients have been enrolled at the recommended dose (median age 60 [35-74]; median PS 0) and have received 29 courses. The median number of prior chemotherapeutic regimens was 2 (range 1-5) and 1 patient had previously been treated with topotecan. All patients had platinum/paclitaxel resistant disease. There were 3 responses (1 CR, 2 PR) for a response rate of 37.5%. The median time to progression was 2.1 months (range, 1.3 to 7.4) and the median survival has not been reached. The predominant toxicity was hematologic and the toxicities were: grade 4 neutropenia (3/8; 37.5%), febrile neutropenia (3/8; 37.5%), and grade 2 anemia (4/8; 50%). Hematologic toxicity resulted in dose delays in 50% (4/8), dose modifications in 37.5% (3/8) and the use of granulocyte colony-stimulating factor in 25% (2/8) of patients. CONCLUSIONS: Therapy with combination topotecan and vinorelbine in patients with platinum/paclitaxel resistant ovarian cancer is active, but has significant hematologic toxicity. [Table: see text].
Berchuck, A; Secord, AA; Havrilesky, LJ; Wenham, R; Soper, JT; Clarke-Pearson, DL
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