Eribulin mesylate in patients with refractory cancers: a Phase I study

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Eribulin mesylate is a synthetic analog of halichondrin B, distinct from conventional tubulin agents.
• This Phase I study was the first to assess eribulin mesylate in Japanese patients with advanced solid tumors.

Purpose of the Study:

• Determine the recommended dose, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) of eribulin mesylate.
• Evaluate the safety, pharmacokinetics, and antitumor activity of eribulin mesylate in Japanese patients.

Main Methods:

• Phase I clinical trial (NCT00326950) involving 15 Japanese patients with advanced solid tumors.
• Eribulin mesylate administered intravenously on Days 1 and 8 of a 21-day cycle at doses ranging from 0.7 to 2.0 mg/m².
• Assessment of dose-limiting toxicities, safety, pharmacokinetics, and antitumor response.

Main Results:

• Neutropenia was identified as the principal dose-limiting toxicity.
• The recommended dose was determined to be 1.4 mg/m², with the MTD at 2.0 mg/m².
• Common grade 3 or 4 toxicities included neutropenia (67%), febrile neutropenia (33%), and lymphocytopenia (20%). Three patients achieved partial responses.

Conclusions:

• Eribulin mesylate demonstrates manageable tolerability at a dose of 1.4 mg/m² when administered on Days 1 and 8 of a 21-day cycle.
• Neutropenia is the primary dose-limiting toxicity requiring careful monitoring.
• The study established a recommended dose and MTD for eribulin mesylate in this patient population.