Phase I study of gemcitabine using a once every 2 weeks schedule

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Gemcitabine is a novel nucleoside analogue with potential in cancer treatment.
• Determining optimal dosing schedules and maximum tolerated doses (MTD) is crucial for novel chemotherapeutics.
• Previous research suggests gemcitabine's efficacy is schedule-dependent rather than dose-dependent.

Purpose of the Study:

• To determine the MTD of gemcitabine in patients with advanced refractory solid tumors.
• To evaluate the safety and toxicity profile of gemcitabine on a once every two weeks schedule.
• To assess the suitability of this bi-weekly gemcitabine schedule for further clinical investigation.

Main Methods:

• A two-center, Phase I clinical trial was conducted.
• Fifty-two patients with advanced refractory solid tumors were enrolled.
• Patients received gemcitabine at escalating doses (40–5700 mg m-2) on a bi-weekly schedule, with weekly toxicity monitoring.

Main Results:

• The MTD for the bi-weekly gemcitabine schedule was determined to be 5700 mg m-2.
• The dose-limiting toxicity was myelosuppression, primarily neutropenia, with other toxicities including nausea, vomiting, fever, and asthenia.
• A single minor response was observed in a heavily pretreated breast cancer patient.

Conclusions:

• The bi-weekly gemcitabine schedule allows for high dose tolerability, exceeding fourfold the recommended weekly dose.
• Despite the high MTD, this specific dosing schedule is likely not the most effective for gemcitabine therapy.
• The study established a clear safety profile for gemcitabine, supporting its continued investigation with optimized schedules.