Phase I study of vinorelbine by 96-hour infusion in advanced metastatic breast cancer

The purpose of this study was to evaluate the maximum tolerated dose and th e toxicity profile of vinorelbine administered by continuous infusion for 9 6 hours to patients who had received prior chemotherapy for metastatic brea st cancer. Forty-three patients with metastatic breast cancer were treated with vinorelbine s mg intravenously for 10 minutes (day I)followed by conti nuous infusion of vinorelbine for 96 hours. Treatments were repeated every 3 weeks. Eighty-eight percent of the patients had had two or more prior che motherapeutic regimens: 91% had prior doxorubicin therapy and 77% had prior pacli-taxel therapy. All 43 patients were evaluable for toxicity. The medi an age was 49 years. All patients had a performance status less than or equ al to 2 and a life expectancy more than 12 weeks. Eight dose levels were ev aluated, and a total of 182 cycles were given. National Cancer Institute gr ade III or IV granulocytopenia was observed in 64 (35%) cycles. neutropenic fever in 27 (15%) cycles, fatigue (National Cancer Institute grade III or IV) in Is (10%) cycles, and hand-foot syndrome in 8 (4%) cycles. In 17 (9%) cycles, patients were hospitalized. The maximum tolerated dose of this reg imen was determined to be vinorelbine 8 mg intravenously for 10 minutes (da y 1) followed by continuous vinorelbine infusion 11 mg/m(2) for 96 hours. T he dose-limiting toxicity was neutropenic fever and stomatitis.