Abstract |
Eribulin mesylate (Halaven™, E7389) is a synthetic analog of the marine natural product halichondrin B that acts via a mechanism distinct from conventional tubulin-targeted agents. This Phase I study (clinicaltrials.gov identifier: NCT00326950) was the first to investigate eribulin mesylate in Japanese patients. The study determined the recommended dose, MTD, DLTs, safety, pharmacokinetics, and antitumor activity of eribulin administered on Days 1 and 8 of a 21-day cycle in Japanese patients with advanced solid tumors. Fifteen patients received eribulin mesylate 0.7-2.0 mg/m(2) as a 2- to 10-min intravenous injection. Neutropenia was the principal DLT. DLTs were observed in two of six patients treated at 1.4 mg/m(2), and in all three patients at 2.0 mg/m(2). The recommended dose was 1.4 mg/m(2) and the MTD was 2.0 mg/m(2). Neutropenia (67%), lymphocytopenia (20%), febrile neutropenia (33%), and fatigue (13%) were the most common grade 3 or 4 toxicities. Eribulin exhibited triphasic pharmacokinetics with a long terminal half-life, high volume of distribution, and low urinary clearance. Three patients achieved partial responses (two with NSCLC, one with head and neck cancer) at 1.4 mg/m(2) dose level. Eribulin mesylate, administered on Days 1 and 8 of a 21-day cycle, exhibits manageable tolerability at 1.4 mg/m(2). DLT was neutropenia.
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Authors | Toru Mukohara, Shunji Nagai, Hirofumi Mukai, Masayuki Namiki, Hironobu Minami |
Journal | Investigational new drugs
(Invest New Drugs)
Vol. 30
Issue 5
Pg. 1926-33
(Oct 2012)
ISSN: 1573-0646 [Electronic] United States |
PMID | 21887501
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Furans
- Ketones
- eribulin
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Topics |
- Adult
- Aged
- Antineoplastic Agents
(adverse effects, pharmacokinetics, therapeutic use)
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Female
- Furans
(administration & dosage, adverse effects, pharmacokinetics)
- Half-Life
- Humans
- Ketones
(administration & dosage, adverse effects, pharmacokinetics)
- Male
- Maximum Tolerated Dose
- Middle Aged
- Neoplasms
(drug therapy, metabolism)
- Neutropenia
(chemically induced)
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