Phase I/II study of gemcitabine in association with vinorelbine for metastatic breast cancer

Background. Gemcitabine (G) and vinorelbine (V) have favorable safety profi le and antitumor activity in metastatic breast cancer. To exploit their dif ferent mechanism of action and lack of overlapping toxicity, we performed a phase I and II study of G and V in combination. Patients and methods. Fifty-three patients with metastatic breast cancer we re treated. In the dose-finding phase, seven cohorts of patients (22 women) received increasing doses to determine the dose limiting toxicity (DLT) an d maximum tolerated dose (MTD) of the combination. Patients recruited in th e phase II portion of the study (31 women) received the dose level immediat ely below the one defined as MTD (i.e., G 1200 mg/m(2), V 30 mg/m(2), on da y 1 and day 8, every 3 weeks). Results. Dose escalation was discontinued at G 1400 mg/m(2) and V 30 mg/m(2 ) because of toxic death due to thrombocytopenia and CNS hemorrage. No othe r limiting toxicities were observed, and tolerability was similar at all do se levels studied in the escalation portion of the study. The main toxicity was granulocytopenia of grade 3/4 in 36 and 48% of the patients on phase I and II respectively, without episodes of neutropenic fever. Thrombocytopen ia was uncommon. Other side effects were usually mild to moderate. In 46 ev aluable patients, the response rate was 24% (complete response 7%, partial response 17%). Disease stabilization was observed in further 17%. The media n duration of response was 12 months (range 5-14) and the median survival w as 20 months (range 1 to 45+). Conclusions. G and V, on day 1 and 8 of 3-weekly cycles, can safely be admi nistered to patients with metastatic breast cancer at the dose of 1200 and 30 mg/m(2), respectively. The antitumor activity of G and V in combination was similar to that reported when using either drug as single agent.