title: Weekly administration of bendamustine: a phase I study in patients with advanced progressive solid tumours.
abstract: 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.
authors.affiliation: Department of Haematology/Oncology, Hannover Medical School, Germany. Schoeffski.Patrick@MH-Hannover.de
authors.forename: P
authors.initials: P
authors.lastname: Schöffski
authors.forename: G
authors.initials: G
authors.lastname: Seeland
authors.forename: H
authors.initials: H
authors.lastname: Engel
authors.forename: V
authors.initials: V
authors.lastname: Grünwald
authors.forename: H
authors.initials: H
authors.lastname: Paul
authors.forename: K
authors.initials: K
authors.lastname: Merkle
authors.forename: R
authors.initials: R
authors.lastname: Kowalski
authors.forename: A
authors.initials: A
authors.lastname: Ganser
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride