title: Induction chemotherapy, extrapleural pneumonectomy, and postoperative high-dose radiotherapy for locally advanced malignant pleural mesothelioma: a phase II trial.
abstract: BACKGROUND
  Extrapleural pneumonectomy (EPP) and adjuvant high-dose radiation therapy (RT) are associated with a median survival of 3 years in early-stage malignant pleural mesothelioma (MPM) but of less than 1 year in locally advanced disease. Although local control after EPP and RT is excellent, most patients die of distant metastases. We designed this clinical trial to test the feasibility of induction chemotherapy followed by EPP and RT in locally advanced MPM with the ultimate aim of improving survival.
  
  
  METHODS
  Patients with MPM and stage III or IV disease were eligible. Induction therapy was four cycles of gemcitabine and cisplatin. Patients without disease progression by computed tomography underwent EPP followed by adjuvant hemithoracic RT (54 cGy).
  
  
  RESULTS
  From January 2002 to January 2004, 21 patients (17 men, four women; median age 60 years) were entered into the study. Histology was epithelioid in 14 patients and mixed or sarcomatoid five patients. Pretreatment disease stage was III in 13 patients and IV in six patients. Nineteen patients received induction chemotherapy. Response to induction therapy was complete in zero patients, partial in five patients, stable disease in six patients, and progression of disease in eight patients. Eight of nine patients undergoing surgical exploration had EPP. The median survival of all patients was 19 months. Patients who had an EPP had a median survival of 33.5 months. Patients with unresectable tumors had a median survival of 9 months (p = 0.01).
  
  
  CONCLUSIONS
  Induction chemotherapy with gemcitabine and cisplatin followed by EPP and adjuvant RT for locally advanced MPM is feasible and leads to a better median overall survival than that previously reported with EPP and RT alone.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. floresr@mskcc.org
authors.forename: Raja M
authors.initials: RM
authors.lastname: Flores
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Rosenzweig
authors.forename: Ennapadam
authors.initials: E
authors.lastname: Venkatraman
authors.forename: Alain
authors.initials: A
authors.lastname: Vincent
authors.forename: Robert
authors.initials: R
authors.lastname: Heelan
authors.forename: Tim
authors.initials: T
authors.lastname: Akhurst
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011013:Pneumonectomy; D011446:Prospective Studies; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine