Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) As Part of Lung-Sparing Multimodality Therapy in Patients With Malignant Pleural Mesothelioma

J Clin Oncol. 2016 Aug 10;34(23):2761-8. doi: 10.1200/JCO.2016.67.2675. Epub 2016 Jun 20.

Abstract

Purpose: We conducted a two-center phase II study to determine the safety of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) after chemotherapy and pleurectomy-decortication (P/D) as part of a multimodality lung-sparing treatment.

Patients and methods: Patients received up to four cycles of pemetrexed plus platinum. If feasible, P/D was performed. Hemithoracic IMPRINT was administered to a planned dose of 50.4 Gy in 28 fractions. The primary end point was the incidence of grade 3 or greater radiation pneumonitis (RP).

Results: A total of 45 patients were enrolled; 18 were not evaluable (because of disease progression before radiation therapy [RT], n = 9; refusal of surgery or RT, n = 5; extrapleural pneumonectomy at time of surgery, n = 2; or chemotherapy complications, n = 2). A total of 26 patients received pemetrexed plus cisplatin, 18 received pemetrexed plus carboplatin, and four received a combination. Thirteen patients (28.9%) had a partial response, 15 patients (33.3%) experienced disease progression, one patient died during chemotherapy, and all others had stable disease. Eight patients underwent P/D or an extended P/D, and 13 underwent a partial P/D. A total of 27 patients started IMPRINT (median dose, 46.8 Gy; range, 28.8 to 50.4 Gy) and were evaluable for the primary end point (median follow-up, 21.6 months). Six patients experienced grade 2 RP, and two patients experienced grade 3 RP; all recovered after corticosteroid initiation. No grade 4 or 5 radiation-related toxicities were observed. The median progression-free survival and overall survival (OS) were 12.4 and 23.7 months, respectively; the 2-year OS was 59% in patients with resectable tumors and was 25% in patients with unresectable tumors.

Conclusions: Hemithoracic IMPRINT for malignant pleural mesothelioma (MPM) is safe and has an acceptable rate of RP. Its incorporation with chemotherapy and P/D forms a new lung-sparing treatment paradigm for patients with locally advanced MPM.

Trial registration: ClinicalTrials.gov NCT00715611.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Female
  • Humans
  • Lung
  • Male
  • Mesothelioma / surgery
  • Mesothelioma / therapy*
  • Middle Aged
  • Organ Sparing Treatments
  • Pemetrexed / administration & dosage
  • Pleural Neoplasms / surgery
  • Pleural Neoplasms / therapy*
  • Prospective Studies
  • Radiation Pneumonitis / etiology*
  • Radiotherapy, Intensity-Modulated / adverse effects*
  • Radiotherapy, Intensity-Modulated / methods
  • Survival Rate

Substances

  • Pemetrexed
  • Carboplatin
  • Cisplatin

Associated data

  • ClinicalTrials.gov/NCT00715611