title: Trimodality therapy with induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma.
abstract: OBJECTIVE
  Malignant pleural mesothelioma (MPM) remains associated with poor outcome. We examined the results of trimodality therapy with cisplatin-based chemotherapy followed by extrapleural pneumonectomy (EPP) and adjuvant high-dose (50 to 60 Gy) hemithoracic radiation therapy for MPM.
  
  
  METHODS
  We conducted a retrospective review of all patients prospectively evaluated for trimodality therapy protocol between January 2001 and December 2007 in our institution.
  
  
  RESULTS
  A total of 60 patients were suitable candidates. Histology was epithelioid (n = 44) or biphasic (n = 16). Chemotherapy regimens included cisplatin/vinorelbine (n = 26), cisplatin/pemetrexed (n = 24), cisplatin/raltitrexed (n = 6), or cisplatin/gemcitabine (n = 4). EPP was performed in 45 patients, and hemithoracic radiation therapy to at least 50 Gy was administered postoperatively to 30 patients. Completion of the trimodality therapy in the absence of mediastinal node involvement was associated with the best survival (median survival of 59 months v <or= 14 months in the remaining patients, P = .0003). The type of induction chemotherapy had no significant impact on survival. Pathologic nodal status remained a significant predictor of poor survival despite completion of the trimodality therapy. After completion of the protocol, the 5-year disease-free survival was 53% for patients with N0 disease, reaching 75% in patients with ypT1-2N0 and 45% in patients with ypT3-4N0.
  
  
  CONCLUSIONS
  This large, single-center experience with induction chemotherapy followed by EPP and adjuvant high-dose hemithoracic radiation for MPM shows that half of the patients are able to complete this protocol. The results are encouraging for patients with N0 disease. However, N2 disease remains a major factor impacting on survival, despite completion of the entire trimodality regimen.
authors.affiliation: Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. marc.deperrot@uhn.on.ca
authors.forename: Marc
authors.initials: M
authors.lastname: de Perrot
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.forename: B C John
authors.initials: BC
authors.lastname: Cho
authors.forename: Andrea
authors.initials: A
authors.lastname: Bezjak
authors.forename: Masaki
authors.initials: M
authors.lastname: Anraku
authors.forename: Ronald
authors.initials: R
authors.lastname: Burkes
authors.forename: Heidi
authors.initials: H
authors.lastname: Roberts
authors.forename: Ming S
authors.initials: MS
authors.lastname: Tsao
authors.forename: Natasha
authors.initials: N
authors.lastname: Leighl
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.forename: Michael R
authors.initials: MR
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D011013:Pneumonectomy; D011799:Quinazolines / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D012189:Retrospective Studies; D013876:Thiophenes / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D011799:Quinazolines; D013876:Thiophenes; D000068437:Pemetrexed; D003841:Deoxycytidine; D014747:Vinblastine; D006147:Guanine; C068874:raltitrexed; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine