Phase II multicenter clinical trial of pulmonary metastasectomy and isolated lung perfusion with melphalan in patients with resectable lung metastases

J Thorac Oncol. 2014 Oct;9(10):1547-53. doi: 10.1097/JTO.0000000000000279.

Abstract

Introduction: The 5-year overall survival rate of patients undergoing complete surgical resection of pulmonary metastases (PM) from colorectal cancer (CRC) and sarcoma remains low (20-50%). Local recurrence rate is high (48-66%). Isolated lung perfusion (ILuP) allows the delivery of high-dose locoregional chemotherapy with minimal systemic leakage to improve local control.

Methods: From 2006 to 2011, 50 patients, 28 male, median age 57 years (15-76), with PM from CRC (n = 30) or sarcoma (n = 20) were included in a phase II clinical trial conducted in four cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, with 45 mg of melphalan at 37°C, followed by resection of all palpable PM. Survival was calculated according to the Kaplan-Meier method.

Results: Operative mortality was 0%, and 90-day morbidity was mainly respiratory (grade 3: 42%, grade 4: 2%). After a median follow-up of 24 months (3-63 mo), 18 patients died, two without recurrence. Thirty patients had recurrent disease. Median time to local pulmonary progression was not reached. The 3-year overall survival and disease-free survival were 57% ± 9% and 36% ± 8%, respectively. Lung function data showed a decrease in forced expiratory volume in 1 second and diffusing capacity of the alveolocapillary membrane of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 months, compared with preoperative values.

Conclusion: Compared with historical series of PM resection without ILuP, favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in patients with resectable PM from CRC or sarcoma.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Bone Neoplasms / pathology
  • Chemotherapy, Cancer, Regional Perfusion / methods
  • Colorectal Neoplasms / pathology
  • Combined Modality Therapy
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary*
  • Lung Neoplasms / surgery
  • Lung Neoplasms / therapy*
  • Male
  • Melphalan / administration & dosage*
  • Metastasectomy / methods
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Osteosarcoma / pathology
  • Survival Rate
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Melphalan