Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: a phase II prospective study

J Thorac Cardiovasc Surg. 2009 Aug;138(2):405-11. doi: 10.1016/j.jtcvs.2009.02.046.


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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • Combined Modality Therapy
  • Female
  • Hot Temperature
  • Humans
  • Intraoperative Care*
  • Kidney / drug effects
  • Male
  • Mesothelioma / drug therapy
  • Mesothelioma / mortality
  • Mesothelioma / secondary
  • Mesothelioma / surgery*
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Pleural Neoplasms / drug therapy
  • Pleural Neoplasms / mortality
  • Pleural Neoplasms / surgery*
  • Pneumonectomy*
  • Postoperative Complications
  • Survival Rate
  • Therapeutic Irrigation


  • Antineoplastic Agents
  • Cisplatin