title: Induction chemotherapy, extrapleural pneumonectomy, and radiotherapy in the treatment of malignant pleural mesothelioma: the Memorial Sloan-Kettering experience.
abstract: Approximately 25% of patients with malignant pleural mesothelioma (MPM) prove unresectable at surgery and the median survival of stage III MPM is <12 months even after complete resection by extrapleural pneumonectomy. From 1939-2004, a series of sequential clinical trials has been performed at our institution. The surgical procedure has been modified and improved upon, and adjuvant hemithoracic radiation (RT) standardized. The evolution of our current standard of care for MPM is discussed. Improving chemotherapy for MPM led us to test induction chemotherapy followed by EPP and adjuvant RT for locally advanced MPM to assess feasibility. Patients with T3-4 or N2 MPM by CT and PET scans were enrolled on a phase II study. Induction therapy was: gemcitabine (1250 mg/m2 days 1, 8) and cisplatin (75 mg/m2 day 8)x2-4 cycles. Patients underwent EPP 3-5 weeks after induction therapy, then 54 Gy RT 4-6 weeks postop. At surgery, 8/9 had complete resection by EPP with no postoperative deaths. All received planned adjuvant RT. This combined modality approach is feasible for locally advanced MPM, and initial analysis suggests improved resectability. This experience supports additional studies of induction and multimodality therapy, especially with regimens such as cisplatin and pemetrexed which may be better tolerated and more effective.
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room C-879, New York, NY 10021, USA. floresr@mskcc.org
authors.forename: Raja M
authors.initials: RM
authors.lastname: Flores
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005971:Glutamates / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008654:Mesothelioma / Q000473:pathology / Q000628:therapy*; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000473:pathology / Q000628:therapy*; D011013:Pneumonectomy; D018714:Radiotherapy, Adjuvant; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D002945:Cisplatin; D000093542:Gemcitabine