Weekly administration of bendamustine: a phase I study in patients with advanced progressive solid tumours.
BACKGROUND
The cytotoxic agent bendamustine combines a purine-like benzimidazol and alkylating nitrogen mustard group. The clinically tolerated dose for single bolus bendamustine is 215 mg/m2, for fractionated therapy on four consecutive days 85 mg/m2. The maximum tolerated dose of a day 1 and 8 (q4w) 30 min infusion schedule was recently found to be 160 mg/m2, mouth dryness and fatigue were dose-limiting. Our current phase I trial was designed to define the recommended dose of a new weekly short infusion schedule.


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/m2, two patients had dose-limiting toxicity (fatigue grade 3, mouth dryness grade 3, fever grade 4 Common Toxicity Criteria). No dose-limiting events were observed in six patients treated at 60 mg/m2. An intermediate dose level of 70 mg/m2 was studied in three younger, less heavily pretreated patients, was well tolerated and not associated with dose-limiting events. Haematological toxicity was mild except for grade 3-4 lymphocytopenia, occurring in 11 of 12 patients. Bendamustine was found to induce long-lasting panlymphocytopenia with predominant B-cell cytotoxicity.


CONCLUSIONS
The maximum tolerated dose of weekly bendamustine given as a 30-min i.v. infusion is 80 mg/m2, mouth dryness, fatigue and fever are dose-limiting. The recommended dose for phase II trials is 60 mg/m2.
Schöffski
P
P
Department of Haematology/Oncology, Hannover Medical School, Germany. Schoeffski.Patrick@MH-Hannover.de
Seeland
G
G
Engel
H
H
Grünwald
V
V
Paul
H
H
Merkle
K
K
Kowalski
R
R
Ganser
A
A
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069461:Bendamustine Hydrochloride; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008017:Life Expectancy; D018655:Lymphocyte Count; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage* / Q000009:adverse effects
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride