FDA Drug Approval Summaries: Pemetrexed (Alimta®)
Open Access
- 1 September 2004
- journal article
- clinical trial
- Published by Oxford University Press (OUP) in The Oncologist
- Vol. 9 (5) , 482-488
- https://doi.org/10.1634/theoncologist.9-5-482
Abstract
The purpose of this report is to summarize information on pemetrexed (LY231514; MTA; Alimta®; Eli Lilly and Company; Indianapolis, IN), a drug recently approved by the U.S. Food and Drug Administration (FDA). The review of the efficacy and safety of pemetrexed is summarized below. Pemetrexed is a pyrrolopyrimidine antifolate. It inhibits thymidylate synthase, glycinamide ribonucleotide formyltransferase, and dihydrofolate reductase. In a single, randomized, single-blind, multicenter phase III trial, the efficacy and safety of pemetrexed combined with cisplatin (Platinol®; Bristol-Myers Squibb; Princeton, NJ) were compared with those of single-agent cisplatin in 448 patients with malignant pleural mesothelioma. Two hundred twenty-six patients were randomized to receive pemetrexed and cisplatin, while 222 patients were randomized to receive cisplatin alone. The primary study end point was survival. Median survival times were 12.1 months for the pemetrexed plus cisplatin treated arm and 9.3 months for the cisplatin alone arm. Pemetrexed causes myelosuppression. The most common adverse events were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. On February 4, 2004, pemetrexed was approved by the FDA in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m2 administered as an i.v. infusion over 10 minutes on day 1 of each 21-day cycle together with cisplatin at a dose of 75 mg/m2 infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B12 injections prior to the start of therapy and continue these during therapy to reduce severe toxicities. Patients should also receive corticosteroids with chemotherapy to reduce the risk of skin rashes. Approval was based on superior survival as a clinical benefit.Keywords
This publication has 15 references indexed in Scilit:
- New molecular and epidemiological issues in mesothelioma: Role of SV40Journal of Cellular Physiology, 1999
- Protocol for the Examination of Specimens From Patients With Malignant Pleural MesotheliomaArchives of Pathology & Laboratory Medicine, 1999
- Preoperative Tumor Volume Is Associated With Outcome In Malignant Pleural MesotheliomaThe Journal of Thoracic and Cardiovascular Surgery, 1998
- Extrapleural Pneumonectomy in the Multimodality Therapy of Malignant Pleural MesotheliomaAnnals of Surgery, 1996
- The importance of surgical staging in the treatment of malignant pleural mesotheliomaThe Journal of Thoracic and Cardiovascular Surgery, 1996
- A Proposed New International TNM Staging System for Malignant Pleural MesotheliomaChest, 1995
- Weekly high-dose cisplatin in malignant pleural mesotheliomaAnnals of Oncology, 1994
- High-dose methotrexate in the treatment of malignant mesothelioma of the pleura. A phase II studyBritish Journal of Cancer, 1992
- Deterioration in lung function following hemithorax irradiation for pleural mesotheliomaInternational Journal of Radiation Oncology*Biology*Physics, 1991
- The Pathogenesis of Asbestos-Associated DiseasesNew England Journal of Medicine, 1982