title: Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: a phase II prospective study.
abstract: OBJECTIVE
  We sought to prospectively determine the feasibility and safety of hyperthermic intraoperative intracavitary cisplatin perfusion immediately after extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma.
  
  
  METHODS
  Patients with malignant pleural mesothelioma who were surgical candidates underwent extrapleural pneumonectomy followed by hyperthermic intraoperative intracavitary cisplatin perfusion, consisting of a 1-hour lavage of the chest and abdomen with cisplatin (42 degrees C) at 225 mg/m(2). Pharmacologic cytoprotection consisted of intravenous sodium thiosulfate with or without amifostine. Morbidity and mortality were recorded prospectively.
  
  
  RESULTS
  Ninety-six (79%) of 121 enrolled patients underwent extrapleural pneumonectomy, of whom 92 (76%) received hyperthermic intraoperative intracavitary cisplatin perfusion after extrapleural pneumonectomy. Fifty-three (58%) patients had epithelial tumors, and 39 (42%) had nonepithelial histology. Hospital mortality was 4.3%. Morbidity (grade 3 or 4, 49%) included atrial fibrillation in 22 (23.9%) patients, venous thrombosis in 12 (13%) patients, and laryngeal nerve dysfunction in 10 (11%) patients. Nine patients had renal toxicity, which was attributable to cisplatin in 8 of them. Among the 27 patients who also received amifostine (910 mg/m(2)), 1 patient had grade 3 renal toxicity attributable to cisplatin. Recurrence of malignant pleural mesothelioma was documented in 47 (51%) patients, with ipsilateral recurrence in 17.4% of patients. The median survival of the 121 enrolled patients was 12.8 months.
  
  
  CONCLUSIONS
  Hyperthermic intraoperative intracavitary cisplatin perfusion following extrapleural pneumonectomy can be performed with acceptable morbidity and mortality. The use of amifostine in addition to sodium thiosulfate might reduce cisplatin-associated renal toxicity. Hyperthermic intraoperative intracavitary cisplatin perfusion following extrapleural pneumonectomy might enhance local control in the chest.
authors.affiliation: Department of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Tamara R
authors.initials: TR
authors.lastname: Tilleman
authors.forename: William G
authors.initials: WG
authors.lastname: Richards
authors.forename: Lambros
authors.initials: L
authors.lastname: Zellos
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
authors.forename: Michael T
authors.initials: MT
authors.lastname: Jaklitsch
authors.forename: Jordan
authors.initials: J
authors.lastname: Mueller
authors.forename: Beow Yong
authors.initials: BY
authors.lastname: Yeap
authors.forename: Aneil A
authors.initials: AA
authors.lastname: Mujoomdar
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Ducko
authors.forename: Raphael
authors.initials: R
authors.lastname: Bueno
authors.forename: David J
authors.initials: DJ
authors.lastname: Sugarbaker
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D005260:Female; D006358:Hot Temperature; D006801:Humans; D007430:Intraoperative Care; D007668:Kidney / Q000187:drug effects; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000601:surgery*; D011013:Pneumonectomy; D011183:Postoperative Complications; D015996:Survival Rate; D007507:Therapeutic Irrigation
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin