Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial)

Our plain-English summary of Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial), by S. Hasegawa, M. Okada, F. Tanaka, et al (International Journal of Clinical Oncology, 2016).

The study

• Authors: S. Hasegawa, M. Okada, F. Tanaka, T. Yamanaka, T. Soejima, N. Kamikonya, T. Tsujimura, K. Fukuoka, K. Yokoi, T. Nakano
• Journal: International Journal of Clinical Oncology
• Published: 2016;21(3):523-30
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: We conducted a prospective multi-institutional study to determine the feasibility of trimodality therapy (TMT) comprising induction chemotherapy followed by extrapleural pneumonectomy (EPP) and radiation therapy in Japanese patients with malignant pleural mesothelioma (MPM).

Methods: Major eligibility criteria were histologically confirmed diagnosis of MPM, including clinical subtypes T0-3, N0-2, M0 disease; no prior treatment for the disease; age 20-75 years; Eastern Cooperative Oncology Group performance status 0 or 1; predicted postoperative forced expiratory volume >1000 ml in 1 s; written informed consent. Treatment methods comprised induction chemotherapy using pemetrexed (500 mg/m(2)) plus cisplatin (60 mg/m(2)) for three cycles, followed by EPP and postoperative hemithoracic radiation therapy (54 Gy). Primary endpoints were macroscopic complete resection (MCR) rate for EPP and treatment-related mortality for TMT.

Results: Forty-two eligible patients were enrolled: median age 64.5 (range 43-74) years; M:F = 39:3, clinical stage I:II:III = 14:13:15; histological type epithelioid were sarcomatoid; biphasic; others = 28:1:9:4. Of 42 patients, 30 completed EPP with MCR and 17 completed TMT. The trial met the primary endpoints, with an MCR rate of 71 % (30/42) and treatment-related mortality of 9.5 % (4/42). Overall median survival time and 2-year survival rate for 42 registered patients were 19.9 months and 42.9 %, respectively. Two-year relapse-free survival rate of 30 patients who completed EPP with MCR was 37.0 %.

Conclusion: This phase II study met the predefined primary endpoints, but its risk/benefit ratio was not satisfactory.

In plain English

This was a prospective phase II feasibility trial, the Japan Mesothelioma Interest Group 0601 Trial, at 12 institutions in Japan. From May 2008 to November 2010 it enrolled 42 patients (39 men, 3 women) with malignant pleural mesothelioma judged operable. The planned treatment was three cycles of pemetrexed plus cisplatin chemotherapy, then extrapleural pneumonectomy (removal of the pleura and the lung on the affected side), then radiation to that side of the chest. The study did not analyze asbestos exposure. All visible tumor was removed in 30 of the 42 patients (71.4%). Four patients (9.5%) died of treatment-related causes within 84 days after surgery. Only 17 patients (40.5%) completed all three steps. Among all 42 patients, median survival was 19.9 months (95% confidence interval 14.2 to 27.3 months), and 42.9% (95% CI 27.8 to 57.1%) were alive at 2 years. Of the 30 patients whose visible tumor was fully removed, 37.0% were alive without relapse 2 years after surgery. The authors concluded the trial met its two main goals but its balance of risks and benefits was not satisfactory.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective, multi-institutional, single-arm phase II feasibility trial of trimodality therapy
• Who was studied: 42 patients with malignant pleural mesothelioma considered resectable (clinical stage T0-3, N0-2, M0; age 20-75), enrolled from 12 institutions in Japan between May 2008 and November 2010; 39 male, 3 female
• Exposure: This is a treatment study, not an asbestos exposure study. The treatment was three cycles of pemetrexed (500 mg/m2) plus cisplatin (60 mg/m2), then extrapleural pneumonectomy, then hemithoracic radiation of 54 Gy in 30 fractions
• Main results:
  • Induction chemotherapy was completed by 39 of 42 patients (92.9%)
  • Response rate to chemotherapy was 33.3% (95% CI 19.6-49.6%) and disease-control rate was 78.6% (95% CI 63.2-89.7%) among the 42 patients
  • Macroscopic complete resection was achieved in 30 of 42 patients (71.4%)
  • Four treatment-related deaths (9.5%, 4/42), all within 84 days after extrapleural pneumonectomy
  • Grade 3 or greater postoperative complications occurred in 21 of 33 patients who underwent surgery (63.6%)
  • All three treatments were completed by 17 of 42 patients (40.5%)
  • For all 42 registered patients, median overall survival was 19.9 months (95% CI 14.2-27.3 months)
  • For all 42 registered patients, 2-year survival was 42.9% (95% CI 27.8-57.1%)
  • Among the 30 patients who completed extrapleural pneumonectomy with macroscopic complete resection, 19 relapsed; relapse-free survival was 57.6% at 1 year and 37.0% at 2 years after surgery
  • Patients with a preoperative diagnosis of epithelioid histology had significantly longer survival than those with nonepithelioid histology (median 27.3 vs 13.6 months, P = 0.0013)
  • Patients who completed all three treatments (n = 17) had significantly longer survival than those who completed extrapleural pneumonectomy but not the full treatment (n = 13), median 39.4 vs 11.4 months, P = 0.0243
• The authors' conclusion: The authors concluded that trimodality therapy for malignant pleural mesothelioma met the trial's primary endpoints and was feasible in Japan, but that its risk-to-benefit ratio was not satisfactory
• Limitations the authors state:
  • The role of radiation therapy remained unclear, because relapse patterns were similar in patients with or without radiation
  • Many more patients failed to proceed to radiation after surgery than in US and European trials (26% vs 13% and 7%). The authors suggested this may reflect less experience with this treatment at the participating centers, none of which had done more than 20 extrapleural pneumonectomies in the prior 5 years

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pemetrexed (Alimta), Cisplatin, Extrapleural Pneumonectomy (EPP), Mesothelioma, Trimodality Therapy, Chemotherapy, Performance Status.

Related studies

• A feasibility study of induction pemetrexed plus cisplatin followed by pleurectomy/decortication aimed at macroscopic complete resection for malignant pleural mesothelioma — M. Shimokawa, S. Hasegawa, et al. (2013)
• Impact of induction therapy on postoperative outcome after extrapleural pneumonectomy for malignant pleural mesothelioma: does induction-accelerated hemithoracic radiation increase the surgical risk? — P. Mordant, K. McRae, et al. (2016)
• Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma — M. de Perrot, R. Feld, et al. (2016)
• PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy — B.K. Bitanihirwe, M. Meerang, et al. (2014)
• Survival after trimodality therapy for malignant pleural mesothelioma: Radical Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy — S. Bölükbas, C. Manegold, et al. (2011)
• Importance of excision repair cross-complementation group 1 and ribonucleotide reductase M1 as prognostic biomarkers in malignant pleural mesothelioma treated with platinum-based induction chemotherapy followed by surgery — L. Frischknecht, M. Meerang, et al. (2015)

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