Phase I dose finding study evaluating the combination of bendamustine with weekly paclitaxel in patients with pre-treated metastatic breast cancer: RiTa trial.

PURPOSE: The aim of the RiTa trial is to establish a feasible combination of bendamustine and paclitaxel in a weekly schedule in anthracycline pre-treated metastatic breast cancer patients.
METHODS: Starting dose of bendamustine was 50 mg/m(2) and was stepwise increased by 10 mg/m(2) up to 70 mg/m(2). The starting dose of paclitaxel was 60 mg/m(2) and was increased up to 90 mg/m(2). There are five pre-defined dose levels with three patients per dose level (maximum six patients) and six patients in the last dose level according to the Goodman design. Dose-limiting toxicities were defined as severe neutropenia and thrombocytopenia as well as non-haematological toxicities >/=NCI-CTC grade 3 in the first cycle.
RESULTS: No dose-limiting toxicity up to 70 mg/m(2) bendamustine and 90 mg/m(2) paclitaxel occurred during the first cycle. Over all cycles, the following severe haematological toxicities (grade 3 and 4) were documented: neutropenia five patients and anaemia one patient. Relevant grade 3 and 4 non-haematological toxicities over all cycles were fatigue two patients, dyspnoea one patient, infection four patients and bone pain in one patient. Five serious adverse events, but no therapy related death occurred. Five patients showed a complete or partial remission, six patients stable disease and six progressed during treatment. The median progression-free survival was 8 months.
CONCLUSION: Treatment with weekly bendamustine and paclitaxel is a feasible and effective regimen in patients with metastatic breast cancer. The recommended dose for forthcoming phase II study is 70 mg/m(2) bendamustine and 90 mg/m(2) paclitaxel.