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Retreatment with pemetrexed can prolong survival in mesothelioma relapse cases

Mesothelioma patients whose tumors shrank after receiving pemetrexed-based chemotherapy may respond well to a second round of treatment if they suffer a relapse of the disease.


Between October 2004 and July 2009, a team of Italian researchers tested the responses of 31 patients with malignant pleural mesothelioma to second-line pemetrexed-based chemotherapy, or PBC. Fifteen patients were retreated with pemetrexed alone and 16 received a combination of pemetrexed and cisplatin.


In nearly half the cases, 48 percent, the tumors shrunk or stopped growing. The response was best for patients whose tumors did not grow for at least 12 months after the first round of PBC. In these patients, no progression of the disease was observed for 5.5 months, compared to 2.5 months for patients whose tumors progressed less than a year after the first round of therapy.


Malignant pleural mesothelioma is a rare, invariably fatal disease that attacks the lining of the lungs. Between 2,000 and 3,000 new cases are diagnosed each year in the United States, 80 percent of which were caused by asbestos exposure. The disease progresses rapidly, and prognosis is extremely poor: survival is typically no more than six to 18 months after diagnosis.


Pemetrexed, also known as Alitma, has been the subject of numerous studies since the U.S. Food and Drug Administration approved clinical trials in 2002. At the time, cisplatin, approved by the FDA in 1978, was considered the front-line treatment for pleural mesothelioma. But response rates were low, less than 15 percent, and the drug has a long list of adverse side effects.


A German study in 2008 showed that 59 percent of patients treated with pemetrexed in combination with cisplatin experienced no disease progression for up to 5 months. Research at the University of Chicago found that the combination therapy resulted in a median survival time of 12.1 months.


The Italian study, which will appear in the April 2011 issue of the journal Lung Cancer, is encouraging because it affirms previous research that suggested, for the first time, that re-treatment with PBC can increase the survival times for patients who suffer relapse.


The earlier study, conducted in Japan, involved four patients who received a second round of cisplatin and pemetrexed. The researchers reported that retreatment seemed to work in patients who saw no disease progression for six months after the initial chemotherapy.


Both the Italian and Japanese studies reported relatively mild side effects following re-treatment.