Pemetrexed in Recurrent or Progressive Central Nervous System Lymphoma: A Phase I Multicenter Clinical Trial

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• No standard salvage treatment exists for relapsed/refractory central nervous system (CNS) lymphoma (CNSL).
• Pemetrexed, an antifolate, was investigated for its potential in CNSL treatment.
• This study aimed to determine the safety, tolerability, and maximum tolerated dose (MTD) of pemetrexed in recurrent CNSL patients.

Purpose of the Study:

• To evaluate the safety and tolerability of pemetrexed in patients with relapsed or refractory CNSL.
• To determine the maximum tolerated dose (MTD) of pemetrexed in this patient population.
• To assess the preliminary activity of pemetrexed as a monotherapy for recurrent CNSL.

Main Methods:

• A phase I study involving 17 patients with relapsed/refractory CNSL.
• Pemetrexed was administered every 2 weeks, with dose escalation from 600 mg/m² to 1200 mg/m².
• The maximum tolerated dose (MTD) was established at 900 mg/m².

Main Results:

• The MTD of pemetrexed was determined to be 900 mg/m² every 2 weeks.
• Common adverse events included fatigue, anemia, and neutropenia, which were generally manageable.
• Among 14 evaluable patients, 21.4% achieved a complete response and 35.7% achieved a partial response.

Conclusions:

• Pemetrexed at 900 mg/m² every 2 weeks demonstrates single-agent activity in recurrent CNSL.
• The drug is well-tolerated and manageable in an outpatient setting.
• Pemetrexed represents a viable treatment option for pretreated patients with CNSL.