Adding a second round of chemotherapy with the drug pemetrexed can slow cancer progression in patients with pleural mesothelioma, according to a recent study in the Journal of Clinical Oncology.
Malignant pleural mesothelioma, which affects the lining of the lungs (pleura), is one of the toughest cancers for doctors to combat. “The tumor itself is the challenge, as it is practically incurable and hardly treatable,” says Jacek Jassem, MD, PhD, professor of Medicine at the Medical University of Gdansk in Poland. Surgery isn’t appropriate for most patients, and radiation has limited effectiveness.
One of the most effective treatments discovered so far is the combination of an anti-metabolite (a class of chemotherapy drugs that interfere with DNA production to halt tumor growth) and a platinum-based drug such as cisplatin. Although many patients stop after initial treatment with these drugs, Dr. Jassem and his colleagues wanted to see what might happen if patients were treated with a second round of chemotherapy.
The phase III study included 243 patients with advanced pleural mesothelioma who had already undergone chemotherapy treatment. About half of the patients were randomly assigned to receive the anti-metabolite chemotherapy drug pemetrexed plus best supportive care (which included nutritional support and pain control), while the other half of participants received best supportive care alone. Researchers measured the patients’ tumors before the start of the study, and then at six-week intervals.
Pemetrexeb plus best supportive care slowed disease progression and improved treatment response compared to best supportive care alone. The cancer was controlled temporarily in about 60% of the patients given pemetrexed, compared with only about 20% of patients in the best supportive care group.
Receiving pemetrexed in addition to best supportive care didn’t offer any real improvement in overall survival, though. “Better response rates and time-to-event variables are not always (I would say seldom) translated into overall survival benefit,” Dr. Jassem says. The main reason for this was that a higher number of best supportive care patients received pemetrexed after discontinuing the study treatment. However, among the 18 percent of patients who responded to treatment in the pemetrexed group, average overall survival rose to more than 20 months.
Although there were side effects from pemetrexed (such as abnormally low white blood cell levels, fatigue, and chest pain), this study showed that second-line chemotherapy can slow disease progression in patients with pleural mesothelioma. The benefit of additional chemotherapy is significant, and this treatment should be considered on an individualized basis, according to Dr. Jassem.
In the future molecular biology might yield new treatments for pleural mesothelioma, but considering the difficult-to-treat nature of this disease, there has been only minor progress in therapies to date. “There is a sore need for further research in this area,” Dr. Jassem says.
Jassem, J, et al. Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. Journal of Clinical Oncology. 2008;26:1698-1704.