phase I study
Springer Online Journal Archives 1860-2000
Abstract Background:The cytotoxic agent bendamustine combines apurine-like benzimidazol and alkylating nitrogen mustard group. The clinicallytolerated dose for single bolus bendamustine is 215 mg/m2, forfractionated therapy on four consecutive days 85 mg/m2. The maximumtolerated dose of a day 1 and 8 (q4w) 30 min infusion schedule was recentlyfound to be 160 mg/m2, mouth dryness and fatigue weredose-limiting. Our current phase I trial was designed to define therecommended dose of a new weekly short infusion schedule. Patients and methods:Patients with refractory malignant tumoursqualified for the trial after written informed consent was obtained.Bendamustine was given as a 30-min i.v. infusion weekly for up to eightconsecutive 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 80mg/m2, two patients had dose-limiting toxicity (fatigue grade 3,mouth dryness grade 3, fever grade 4 Common Toxicity Criteria). Nodose-limiting events were observed in six patients treated at 60mg/m2. An intermediate dose level of 70 mg/m2 wasstudied in three younger, less heavily pre-treated patients, was welltolerated and not associated with dose-limiting events. Haematologicaltoxicity was mild except for grade 3–4 lymphocytopenia, occurring in 11of 12 patients. Bendamustine was found to induce long-lastingpanlymphocytopenia with predominant B-cell cytotoxicity. Conclusions:The maximum tolerated dose of weekly bendamustinegiven as a 30-min i.v. infusion is 80 mg/m2, mouth dryness, fatigueand fever are dose-limiting. The recommended dose for phase II trials is 60mg/m2.
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