SAN FRANCISCOAdding vitamin B12 and folic acid to chemotherapy
with 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 neutropeniaall 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.