Weekly administration of bendamustine: A phase I study in patients with advanced progressive solid tumours

Background: The cytotoxic agent bendamustine combines a purine-like benzimi dazol and alkylating nitrogen mustard group. The clinically tolerated dose for single bolus bendamustine is 215 mg/m(2), for fractionated therapy on f our consecutive days 85 mg/m(2). The maximum tolerated dose of a day 1 and 8 (q4w) 30 min infusion schedule was recently found to be 160 mg/m(2), mout h dryness and fatigue were dose-limiting. Our current phase I trial was des igned to define the recommended dose of a new weekly short infusion schedul e. Patients and methods: Patients with refractory malignant tumours qualified for the trial after written informed consent was obtained. Bendamustine was given as a 30-min i.v. infusion weekly for up to eight consecutive weeks. Results: Twelve patients (8 male, 4 female, median age 57.5 years, range 42 -64) were enrolled in this trial. At the starting dose of 80 mg/m(2), two p atients had dose-limiting toxicity (fatigue grade 3, mouth dryness grade 3, fever grade 4 Common Toxicity Criteria). No dose-limiting events were obse rved in six patients treated at 60 mg/m(2). An intermediate dose level of 7 0 mg/m(2) was studied in three younger, less heavily pre-treated patients, was well tolerated and not associated with dose-limiting events. Haematolog ical toxicity was mild except for grade 3-4 lymphocytopenia, occurring in 1 1 of 12 patients. Bendamustine was found to induce long-lasting panlymphocy topenia with predominant B-cell cytotoxicity. Conclusions: The maximum tolerated dose of weekly bendamustine given as a 3 0-min i.v. infusion is 80 mg/m(2), mouth dryness, fatigue and fever are dos e-limiting. The recommended dose for phase II trials is 60 mg/m(2).