Phase I trial of PALA

Area of Science:

• Oncology
• Clinical Pharmacology

Background:

• Advanced malignant tumors present significant treatment challenges.
• Parenteral administration of novel chemotherapeutic agents requires thorough safety and efficacy evaluation.

Purpose of the Study:

• To determine the maximum tolerated dose (MTD) of PALA administered intravenously on a weekly schedule.
• To characterize the toxicity profile and preliminary efficacy of PALA in patients with advanced malignancies.

Main Methods:

• A phase I dose-escalation study involving 32 patients with advanced malignant tumors.
• PALA was administered intravenously at eight dose levels (900–6750 mg/m2) over a weekly schedule (three doses per course).
• Toxicity, including gastrointestinal, dermatologic, neurologic, renal, and hepatic effects, was closely monitored.

Main Results:

• Dose-limiting toxicities included gastrointestinal distress (diarrhea) and skin rash.
• No consistent myelosuppression, renal, or hepatic toxicity was observed.
• Two patients experienced encephalopathy and seizures; minor tumor responses were noted in three patients (lung adenocarcinoma, bladder epidermoid carcinoma).

Conclusions:

• Recommended doses for phase II studies are 4500 mg/m2/week for patients with performance status ≥70 and 3750 mg/m2/week for those with lower performance status.
• PALA exhibits a manageable toxicity profile with specific dose recommendations based on patient performance status for further investigation.