Phase II trial of Extrapleural Pneumonectomy with Phase II trial of Extrapleural Pneumonectomy with Intraoperative Intrathoracic/Intraperitoneal Heated Cisplatin for Malignant Pleural Mesothelioma
Tamara R. Tilleman1, William G. Richards1, Lambros Zellos1, Bruce E. Johnson2, Michael T. Jaklitsch1, Christopher T. Ducko1, Jordan Mueller1, Raphael Bueno1, David J. Sugarbaker1; 1Thoracic Surgery, Brigham and Women's Hospital, Boston, MA; 2Dana Farber Cancer Institute, Boston, MA
Comment on this Abstract
Objective: To determine the feasibility and safety of treating malignant pleural mesothelioma (MPM) patients with hyperthermic intraoperative intracavitary cisplatin perfusion (HIOC)
Methods: This study registered 121 patients with confirmed MPM who were candidates for extrapleural pneumonectomy (EPP) in an intent-to-treat design. Patients underwent EPP followed by HIOC. HIOC consisted of a 1-hour lavage of the chest and abdomen with cisplatin (41°C; 225 mg/m2), at the maximal tolerated dose (J Clin Oncol 10:1561-7, 2006). Intravenous sodium thiosulfate was administered following HIOC. A subset of patients also received intraoperative IV amifostine prior to HIOC.
Patients were followed prospectively for morbidity and mortality.
Results: Of 121 patients, 96 were resectable (79%). Twenty-five were unresectable due to tumor involvement of chest wall (21) or vessels (3) or diffuse metastatic disease (1). Four of the 96 patients resectable by EPP did not receive HIOC treatment per protocol: 3 due to intraoperative hemodynamic instability; 1 patient had partial duration HIOC due to a technical failure of the perfusion system.
Among the 92 resectable patients who received treatment per protocol, the median age was 60 years, and the median hospitalization was 12 days. Pathologic staging of this cohort by Brigham criteria (J Thorac Cardiovasc Surg 1999; 117:54-65) revealed six stage I, 23 stage II and 63 stage III. Fifty-eight patients had epithelial and 34 had sarcomatoid or mixed histology.
Perioperative mortality rate was 1% (1/92 patients died of cardiac arrest) among resectable patients and 1.7% (2/121) among all patients.
Perioperative grade 4 morbidity among resectable cases included 6 patients with thromboembolism (7%), 6 metabolic acidosis (7%), 5 atrial fibrillation (5%), 5 ARDS (5%), 3 prolonged intubation (3%). Among 64 patients treated only with thiosulfate, 4 had grade 3 renal toxicity and 3 had grade 4. Among 26 patients who also received amifostine, one had grade 3 renal toxicity and none had grade 4 (IMIG Conf. 2006).
Conclusion: 1. EPP can be performed with acceptable morbidity and low mortality in the setting of HIOC
2. HIOC is feasible and safe and does not contribute significant perioperative morbidity or mortality.
3. Strategies involving pharmacologic cytoprotection allow high-dose cisplatin perfusion without significant renal toxicity.
4. EPP with HIOC represents a novel platform for cisplatin delivery including future multi-drug combinations.
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