Taxol administered as a 120 hour infusion

Area of Science:

• Oncology
• Clinical Pharmacology

Background:

• Paclitaxel (Taxol) is a key chemotherapy agent.
• Determining optimal dosing and schedules is crucial for efficacy and safety.

Purpose of the Study:

• To evaluate the safety and tolerability of paclitaxel administered as a 120-hour infusion every 3 weeks in patients with advanced cancer.
• To identify the dose-limiting toxicity and establish a recommended dose for Phase II trials.

Main Methods:

• A Phase I clinical trial involving 20 patients with advanced cancer.
• Dose escalation of paclitaxel from 5 mg/m2/d up to 36 mg/m2/d, delivered as a 120-hour infusion every 3 weeks.
• Evaluation of toxicity, including leukopenia, mucositis, neurotoxicity, cardiotoxicity, and hypersensitivity reactions.

Main Results:

• Grade 4 leukopenia was the dose-limiting toxicity at 36 mg/m2/d (50% of patients).
• Significant mucositis was observed at 30 and 36 mg/m2/d.
• All toxicities resolved within 3 weeks, with no cumulative toxicity, neurotoxicity, cardiotoxicity, or hypersensitivity reactions noted.

Conclusions:

• The recommended dose for Phase II testing of paclitaxel on this schedule is 30 mg/m2/d.
• This dosing schedule demonstrates manageable toxicity in patients with advanced cancer.