ORLANDOPemetrexed (Alimta) plus 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 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 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 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%.