SAN FRANCISCO—Adding vitamin B12 and folic acid(Drug information on folic acid) to chemotherapy with pemetrexed(Drug information on pemetrexed) disodium (Alimta) reduces the incidence of severe life-threatening toxicities, according to research presented at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 300).
Pemetrexed disodium is an investigational, novel, multitargeted antifolate with inhibitory activity against multiple enzymes involved in non-small-cell lung cancer (NSCLC), mesothelioma, and breast, pancreas, colorectal, gastric, cervical, and head and neck cancers, said lead investigator Paul Bunn, Jr., MD, University of Colorado Health Sciences Center, Denver.
It offers convenient administration (10-minute intravenous infusion every 21 days) and can be combined, often at full dose, with other active drugs.
Unpredictable, severe toxicities, however, have been a problem with antifolates and antimetabolites in general. These have included neutropenia, thrombocytopenia, mucositis, and febrile neutropenia—all significantly correlated with drug-related death, Dr. Bunn said.
"When you have falling blood counts together with mucositis, infection is very common. There has never been a good way to predict who will get these toxicities, especially the severe ones, or to prevent them, again especially the severe ones," Dr. Bunn said in an interview with ONI.
Dr. Bunn and his colleagues observed that folate and vitamin B12 nutritional status affect the toxicity of antimetabolites, particularly those targeting thymidylate synthase. Specifically, they had seen that B12 and folate pools, as assessed by plasma homocysteine and methylmalonic acid, correlated with severe toxicity, with high homocysteine levels indicating folate deficiency.
The tip-off, according to co-investigator Paolo Paoletti, MD, director of clinical research, Eli Lilly, was that in multinational early trials of pemetrexed disodium, baseline levels of homocysteine were higher among European patients than among American patients. "We knew that the USDA requires vitamin supplementation in US diets and that many Americans take multivitamins," Dr. Paoletti said.
