OBJECTIVE: The purpose of this study was to define the maximum tolerated dose (MTD) of topotecan given as escalating doses combined to a fixed dosage of carboplatin in late relapsing ovarian carcinomas. METHODS: Women with relapsing ovarian cancer more than 6 months after first-line treatment were eligible for the study. In the first phase of the trial, patients were allocated to escalating topotecan doses with a carboplatin fixed dose (AUC 5, according to Cockcroft's formula). If no "severe" adverse event occurred in 1 or more of the patients, the topotecan dose was increased. The starting dose of topotecan was 0.50 mg/m(2)/day, for 3 consecutive days, and the dose step was of 0.25 mg/m(2)/day, till 1.5 mg/m(2)/day. The study progressed then in a phase II trial. RESULTS: A total of 39 patients entered the trial. Twenty took part in the escalating topotecan dose phase (4 per dose level, 0.50, 0.75, 1, 1.25, and 1.50 mg/m(2)/day) and 19 in the phase II. No severe adverse event was observed in the phase I of the trial, so the MTD was not reached. In the phase II trial topotecan was given to 1 mg/m(2)/day. Overall grade 3-4 neutropenia, lasting 7 days or less, was observed in 58.9% (23 patients). Thrombocytopenia occurred in 30.8% (12 patients) and grade 3 anemia in 25.6% (10 patients) of subjects. No life-threatening event occurred. Platelets or red blood cell transfusions were given in three cases (7.8%). CONCLUSIONS: This daily-times-3-day schedule of topotecan in combination with carboplatin is safe. (c)2001 Elsevier Science.
OBJECTIVE: The purpose of this study was to define the maximum tolerated dose (MTD) of topotecan given as escalating doses combined to a fixed dosage of carboplatin in late relapsing ovarian carcinomas. METHODS:Women with relapsing ovarian cancer more than 6 months after first-line treatment were eligible for the study. In the first phase of the trial, patients were allocated to escalating topotecan doses with a carboplatin fixed dose (AUC 5, according to Cockcroft's formula). If no "severe" adverse event occurred in 1 or more of the patients, the topotecan dose was increased. The starting dose of topotecan was 0.50 mg/m(2)/day, for 3 consecutive days, and the dose step was of 0.25 mg/m(2)/day, till 1.5 mg/m(2)/day. The study progressed then in a phase II trial. RESULTS: A total of 39 patients entered the trial. Twenty took part in the escalating topotecan dose phase (4 per dose level, 0.50, 0.75, 1, 1.25, and 1.50 mg/m(2)/day) and 19 in the phase II. No severe adverse event was observed in the phase I of the trial, so the MTD was not reached. In the phase II trial topotecan was given to 1 mg/m(2)/day. Overall grade 3-4 neutropenia, lasting 7 days or less, was observed in 58.9% (23 patients). Thrombocytopenia occurred in 30.8% (12 patients) and grade 3 anemia in 25.6% (10 patients) of subjects. No life-threatening event occurred. Platelets or red blood cell transfusions were given in three cases (7.8%). CONCLUSIONS: This daily-times-3-day schedule of topotecan in combination with carboplatin is safe. (c)2001 Elsevier Science.