Ulrich Gatzemeier, MD

Malignant pleural mesothelioma (MPM) is a disease with a poorprognosis, related in part to the aggressiveness of this disease, and inpart due to the lack of drugs that have demonstrated tumor activity.Historically, antifolates such as methotrexate have been the most activedrugs in the treatment of mesothelioma. Newer antifolates haverecently demonstrated higher efficacy than older regimens in the treatmentof this rare disease. One of these agents, pemetrexed (Alimta),has been evaluated both as a single agent and as part of a combinationregimen. Pemetrexed has been studied in three trials in patients withMPM, and two phase I trials included patients with MPM. In a phaseII trial, pemetrexed was studied as a single agent in patients with MPM.Seven of 64 patients achieved partial responses, with a median overallsurvival of 10.7 months. A large, randomized, phase III trial was conductedto compare pemetrexed/cisplatin with cisplatin. The responserate was 41.3% compared with 16.7%, median survival was 12.1 monthscompared with 9.3 months, and 1-year survival was 50.3% vs 38% inthe pemetrexed/cisplatin and cisplatin arms, respectively. The combinationof pemetrexed/cisplatin also demonstrated superiority in qualityof life and pulmonary functioning analysis when compared withcisplatin.

Non–small-cell lung cancer represents a growing global burden andremains a therapeutic challenge. Only small improvements in survivalhave been made with standard chemotherapeutic approaches to advanceddisease in recent history. Novel biologic targeted therapies offerthe potential of improving patient management and treatment outcomesin non–small-cell lung cancer. Prominent among these novelagents are the HER1/epithelial growth factor receptor (EGFR) inhibitors.One of these agents, gefitinib (Iressa), is already approved for usein advanced, refractory non–small-cell lung cancer. Erlotinib (Tarceva)is a promising HER1/EGFR inhibitor in phase III evaluation as firstlinetherapy combined with chemotherapy and as second-/third-linemonotherapy in advanced non–small-cell lung cancer. In addition,erlotinib is being evaluated in combination with the angiogenesis inhibitorbevacizumab (Avastin), a strategy combining two new modalitiesin cancer treatment. Results of these trials will provide importantinformation on optimal use of these new targeted therapies and mayoffer the promise of improving the treatment of non–small-cell lungcancer.

Despite the availability of combination chemotherapy, response rates are poor in patients with non–small-cell lung cancer. Recently, phase II trials have been undertaken with single-agent paclitaxel (Taxol). Good results have