title: Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial).
abstract: OBJECTIVE
  We conducted a prospective multi-institutional study to determine the feasibility of trimodality therapy (TMT) comprising induction chemotherapy followed by extrapleural pneumonectomy (EPP) and radiation therapy in Japanese patients with malignant pleural mesothelioma (MPM).
  
  
  METHODS
  Major eligibility criteria were histologically confirmed diagnosis of MPM, including clinical subtypes T0-3, N0-2, M0 disease; no prior treatment for the disease; age 20-75 years; Eastern Cooperative Oncology Group performance status 0 or 1; predicted postoperative forced expiratory volume >1000 ml in 1 s; written informed consent. Treatment methods comprised induction chemotherapy using pemetrexed (500 mg/m(2)) plus cisplatin (60 mg/m(2)) for three cycles, followed by EPP and postoperative hemithoracic radiation therapy (54 Gy). Primary endpoints were macroscopic complete resection (MCR) rate for EPP and treatment-related mortality for TMT.
  
  
  RESULTS
  Forty-two eligible patients were enrolled: median age 64.5 (range 43-74) years; M:F = 39:3, clinical stage I:II:III = 14:13:15; histological type epithelioid were sarcomatoid; biphasic; others = 28:1:9:4. Of 42 patients, 30 completed EPP with MCR and 17 completed TMT. The trial met the primary endpoints, with an MCR rate of 71 % (30/42) and treatment-related mortality of 9.5 % (4/42). Overall median survival time and 2-year survival rate for 42 registered patients were 19.9 months and 42.9 %, respectively. Two-year relapse-free survival rate of 30 patients who completed EPP with MCR was 37.0 %.
  
  
  CONCLUSIONS
  This phase II study met the predefined primary endpoints, but its risk/benefit ratio was not satisfactory.
authors.affiliation: Department of Thoracic Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan. hasegawa@hyo-med.ac.jp.
authors.forename: Seiki
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan.
authors.forename: Morihito
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Surgery, University of Occupational and Environmental Health, Kitakyusyu, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Department of Biostatistics, Yokohama City University, Yokohama, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Department of Radiation Oncology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Soejima
authors.affiliation: Department of Radiation Oncology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kamikonya
authors.affiliation: Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsujimura
authors.affiliation: Department of Medical Oncology, Sakai Hospital, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Fukuoka
authors.affiliation: Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Yokoi
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007564:Japan; D008297:Male; D008654:Mesothelioma / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D000068437:Pemetrexed / Q000008:administration & dosage; D010997:Pleural Neoplasms / Q000473:pathology / Q000628:therapy*; D011013:Pneumonectomy; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D000068437:Pemetrexed; D002945:Cisplatin
keywords: Clinical trials; Mesothelioma; Pleural disease; Thoracic surgery