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

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Bendamustine is a cytotoxic agent combining benzimidazole and nitrogen mustard.
• Previous studies established tolerated doses for bolus and fractionated bendamustine regimens.
• A weekly 30-min infusion schedule's maximum tolerated dose (MTD) was previously found to be 160 mg/m2, with dose-limiting toxicities of mouth dryness and fatigue.

Purpose of the Study:

• To define the recommended dose of a novel weekly short infusion schedule for bendamustine.
• To evaluate the safety and tolerability of bendamustine administered weekly via 30-min IV infusion in patients with refractory malignant tumors.

Main Methods:

• A phase I clinical trial was conducted with patients providing informed consent.
• Bendamustine was administered as a 30-minute intravenous infusion weekly for up to eight weeks.
• Dose escalation followed a standard phase I design to determine the MTD.

Main Results:

• Twelve patients were enrolled, with dose escalation starting at 80 mg/m2.
• Dose-limiting toxicities (fatigue, mouth dryness, fever) were observed at 80 mg/m2.
• A dose of 60 mg/m2 was well-tolerated, with no dose-limiting events observed in six patients. Grade 3-4 lymphocytopenia was common.

Conclusions:

• The maximum tolerated dose (MTD) for weekly bendamustine given as a 30-min IV infusion is 80 mg/m2.
• Dose-limiting toxicities include mouth dryness, fatigue, and fever.
• The recommended dose for phase II trials is 60 mg/m2, demonstrating a favorable safety profile.