An experimental anti-cancer drug, pemetrexed, is continuing to show increasing promise for patients with malignant mesothelioma (cancer of the lining of the chest and abdomen), according to research reported in the August 15 issue of the Journal of Clinical Oncology (Vol. 20, No. 16: 3533-3544).

The previously untested combination of pemetrexed (Alimta) plus the established chemotherapy drug carboplatin stretched patients' survival to an average of 15 months, almost doubling the eight-to-nine month average experts say is more typical with other mesothelioma therapies.

"This drug combination showed remarkable activity in mesothelioma," noted the trial study author, professor Hilary Calvert of the Cancer Research Unit at Newcastle University, in Newcastle-Upon-Tyne in England.

About one-third of patients were still alive at the time the study was written, some after almost three years.

Among nearly one-third of the patients, tumors shrank, and more than two-thirds of the patients reported an improvement in symptoms such as pain.

There were relatively few side effects other than temporary declines in the number of infection-fighting white blood cells and platelets (which help stop bleeding).

The researchers noted these problems are likely to be even milder in future trials, because it's now known that adding folic acid and vitamin B12 to patients' diets helps lessen side effects.

"These results are quite gratifying and do indeed suggest that real progress has been made in the treatment of advanced pleural mesothelioma," said mesothelioma expert Nicholas J. Vogelzang, MD, director of the University of Chicago Cancer Research Center in Chicago.

Most chemotherapy drugs are relatively ineffective against advanced mesothelioma, said Vogelzang, so there is no standard therapy for it. Many doctors now recommend treatment only to relieve pain and other symptoms when the disease is advanced, he noted.

In the chest, mesothelioma is usually caused by exposure to asbestos. It is diagnosed in about 2,500 patients in the US every year and twice that many in Europe. Those figures may increase four times in the next eight years, said Vogelzang. That's because many people have already been exposed to asbestos, but the disease will take years to develop and produce symptoms, he noted.

In the 1980s, Calvert and colleagues were instrumental in developing a class of drugs called multitargeted anti-folates (MTAs), which limit cancer cells' access to the B-vitamin folic acid. Mesothelioma cells need folic acid to grow and replicate.

Some first-generation MTAs proved too toxic, but in the 1990s a Princeton biochemistry professor discovered pemetrexed, which interferes with three enzymes that help mesothelioma cells to use folic acid, yet has few serious side effects.

Pemetrexed proved effective against mesothelioma when used with the chemotherapy drug cisplatin (a cousin of carboplatin) in early trials.

Earlier this year, Vogelzang and colleagues reported initial results from the largest mesothelioma trial yet conducted, which included 450 patients. In this study, tumors shrank in 41% of patients on pemetrexed plus cisplatin, compared to 17% treated with cisplatin alone, and patients on the combination survived an average of about one year. The full results of the study will likely be published soon, he noted.

Calvert's study of pemetrexed with carboplatin was begun because carboplatin typically produces fewer side effects than cisplatin, said Vogelzang.

Its successes will make a real difference in the lives of many patients with advanced mesothelioma, he noted.

"The number of patients in this study and the well-tolerated nature of the pemetrexed plus carboplatin combination are going to make this a very popular therapy very quickly when pemetrexed gets out on the market," said Vogelzang.