Advanced Malignant Mesothelioma (Stages II, III, and IV)
In an analysis of all patients who were randomly assigned and treated, the combination of pemetrexed and cisplatin was associated with a statistically significant improvement in survival compared with cisplatin alone; the median survivals were 12.1 versus 9.3 months, respectively (P = .020). The hazard ratio for death of patients in the pemetrexed plus cisplatin arm versus those in the control arm was 0.77. Median time-to-progression was significantly longer in the pemetrexed plus cisplatin arm (5.7 months vs. 3.9 months, P = .001). This superiority in the combination arm was also demonstrated in the vitamin-supplemented subgroup. The median survivals were 13.3 and 10.0 months in the combination group and cisplatin alone group, respectively (P = .051). The principal adverse effects of the pemetrexed plus cisplatin regimen were myelosuppression, fatigue, nausea, vomiting, and dyspnea. Most grade 3 to 4 adverse effects were significantly reduced by vitamin supplementation without any decrease in efficacy.
A randomized phase III trial of 250 patients was performed by the European Organisation for Research and Treatment of Cancer (EORTC-08983) to compare cisplatin alone with the combination of raltitrexed, a thymidine synthase inhibitor, and cisplatin in first-line treatment of patients with malignant pleural mesothelioma. Cisplatin (80 mg/m2 IV) was given on day 1, alone or combined with raltitrexed (3 mg/m2). No toxic deaths resulted, and the main grade 3 or 4 toxicities observed were neutropenia and emesis, which were reported twice as often in the combination arm. Among 213 patients with measurable disease, the response rate was 13.6% versus 23.6%, respectively (P = .056). No difference in quality of life was observed. The combination arm was associated with an increased survival. Median overall and 1-year survival were 8.8 versus 11.4 months, respectively and 40% versus 46%, respectively (P = .048).[Level of evidence: 1iiA]
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with advanced malignant mesothelioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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