ORLANDOPemetrexed (Alimta) plus cisplatin(Drug information on cisplatin) (Platinol) with folic acid/vitamin B12 supplementation should be considered standard front-line therapy for patients with malignant pleural mesothelioma, Nicholas J. Vogelzang, MD, said at the plenary session of the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 5).
Dr. Vogelzang, Fred C. Buffett Professor and director, University of Chicago Cancer Research Center, reported results of an international phase III study, the largest ever in the disease, showing significantly improved survival and improved symptom control with the combination, compared with cisplatin alone.
Malignant pleural mesothelioma is an aggressive cancer of the lining of the lung for which there is no approved or effective chemotherapy. It is associated with exposure to asbestos and occurs from 20 to 40 years after exposure. Pemetrexed(Drug information on pemetrexed) is an experimental antifolate that targets three key enzymes necessary for DNA and RNA synthesis.
The study involved 574 patients who were not candidates for curative surgery and had received no prior chemotherapy. Of these, 456 patients were randomized to receive pemetrexed 500 mg/m² IV over 10 minutes followed 30 minutes later by cisplatin 75 mg/m², both given on day 1 of a 3-week cycle, or cisplatin alone. All patients received dexamethasone(Drug information on dexamethasone) prophylaxis for skin rash. A total of 448 patients were eligible for analysis.
Early on in the study, the protocol was changed due to a high rate of severe toxicity and drug-related death in the pemetrexed arm. This was linked to folic acid deficiency as reflected by elevated homocysteine levels. The remaining patients received oral folic acid(Drug information on folic acid) 350 to 1,000 µg daily and vitamin B12 1,000 µg intramuscularly every 9 weeks in addition to their assigned treatment.
Vitamin supplementation reduced toxicity, allowing fewer treatment interruptions. "The median number of cycles in the combination arm increased from 2 in the never-supplemented patients to 6 in the supplemented patients," Dr. Vogelzang said. "Interestingly, similar results were seen in the cisplatin arm."
The drug-related death rate in the combination arm declined from 7% to 3% after supplementation was instituted. Neutropenia fell from 41% to 23%; febrile neutropenia from 5% to 1%, and vomiting from 21% to 11%.