An overview of neoadjuvant chemotherapy in the multimodality treatment of malignant pleural mesothelioma

Our plain-English summary of An overview of neoadjuvant chemotherapy in the multimodality treatment of malignant pleural mesothelioma, by G. Pasello, G.L. Ceresoli, A. Favaretto (Cancer Treatment Reviews, 2013).

The study

• Authors: G. Pasello, G.L. Ceresoli, A. Favaretto
• Journal: Cancer Treatment Reviews
• Published: 2013;39(1):10-7
• Type of article: Review
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant Pleural Mesothelioma (MPM) is an aggressive tumour with poor prognosis and increasing incidence in industrialized countries because of the previous widespread exposure to asbestos fibres and to the long lag period from time of exposure and the diagnosis of the disease. MPM shows high refractoriety to systemic treatment, single-modality treatment was generally ineffective and did not achieve higher results than supportive care. The incidence of local and distant recurrences after surgery remains high and that was the reason for many centres to perform combined treatments. In the attempt of reducing the incidence of local recurrences, a multimodality approach with surgery followed by adjuvant radiotherapy was explored. Extrapleural pneumonectomy (EPP) allows higher doses of radiotherapy to the whole hemithorax by avoiding pulmonary toxicity and the results of this approach is a significant reduction of loco-regional relapses; although, extrathoracic metastasis represent a major problem in the management of the disease because of the impact on overall survival. The success with surgical resection after neoadjuvant chemotherapy in stage IIIA lung cancer has been the impetus for several groups to apply this strategy in MPM aiming at reducing the incidence of distant relapse after surgery. Platinum-based chemotherapy plus gemcitabine or pemetrexed for 3-4 cycles followed by surgery and postoperative high-dose radiotherapy showed the best results in terms of overall and progression free survival. This review will focus on the main clinical studies and overview the results of different chemotherapy regimens in the neoadjuvant treatment of MPM.

Copyright © 2012 Elsevier Ltd. All rights reserved.

In plain English

This article was a review, not a new study. The authors searched PubMed, the Cochrane database and meeting abstracts for studies of chemotherapy given before surgery (neoadjuvant chemotherapy) in malignant pleural mesothelioma. The approach reviewed was trimodality treatment: chemotherapy, then surgery removing the lung and surrounding lining (extrapleural pneumonectomy), then radiotherapy. It did not examine asbestos exposure. The authors reported that across 8 prospective and 3 retrospective studies, median overall survival ranged from 23 to 29 months in patients who completed trimodality treatment. They described the MARS trial, which randomly assigned 50 patients. Median survival was 14.4 months in the group assigned to extrapleural pneumonectomy and 19.5 months in the group assigned to no extrapleural pneumonectomy. In their own group's retrospective analysis of 54 patients, overall survival was 118 weeks with carboplatin and 66 weeks with cisplatin. The authors concluded that trimodality protocols gave the best results, with survival over 20 months in selected patients. They added that no conclusion could yet be drawn about the best treatment. They noted that no randomized trial had compared chemotherapy regimens given before surgery, and that the phase II studies differed.

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: Review of published clinical studies and meeting abstracts on neoadjuvant chemotherapy in trimodality treatment of malignant pleural mesothelioma
• Who was studied: Published prospective and retrospective clinical studies of patients with malignant pleural mesothelioma who received chemotherapy before surgery. The authors cite 8 prospective and 3 retrospective studies, plus other trials including the MARS trial (UK).
• Exposure: Treatment, not asbestos exposure: preoperative chemotherapy (mainly cisplatin or carboplatin combined with gemcitabine or pemetrexed), followed by extrapleural pneumonectomy and postoperative radiotherapy
• Main results:
  • The review summarized median overall survival as ranging from 23 to 29 months among patients who completed trimodality treatment in the studies reviewed
  • The review stated that the prospective studies using gemcitabine plus a platinum drug before surgery agreed that this did not increase death or complication rates, provided an experienced team managed treatment
  • The review described the MARS trial, in which 24 patients were assigned to extrapleural pneumonectomy and 26 to no extrapleural pneumonectomy. Three patients in the no extrapleural pneumonectomy group had that surgery outside the trial. Median survival from randomization was 14.4 months in the group assigned to extrapleural pneumonectomy and 19.5 months in the group assigned to no extrapleural pneumonectomy (p = 0.016 after adjustment for prognostic factors).
  • In the EORTC trial of cisplatin plus pemetrexed before surgery, the primary endpoint (success of treatment) was reached in 42.1% of patients. This was below the 60% needed to justify further study.
  • The authors' group carried out a retrospective analysis of 54 patients: 30 were given pemetrexed plus carboplatin and 24 were given pemetrexed plus cisplatin. Overall survival was 118 weeks in the carboplatin group and 66 weeks in the cisplatin group.
  • In the authors' group's prospective study of 36 patients, lung function and exercise test measures improved after preoperative chemotherapy
• The authors' conclusion: The authors concluded that trimodality protocols of neoadjuvant chemotherapy followed by extrapleural pneumonectomy and adjuvant radiotherapy achieved the best results, with overall survival longer than 20 months in selected patients. They also stated that the optimal sequence of treatments and the best chemotherapy regimen are not yet defined.
• Limitations the authors state:
  • The authors wrote that two things together do not allow any conclusion about the best treatment: the lack of a randomized study in this setting, and the differences between the available phase II studies
  • The studies included only selected patients who were eligible for trimodality treatment, which introduces bias
  • The studies differed in patient selection, treatment regimens, and methods for follow-up and survival analysis
  • No randomized trial has compared different chemotherapy regimens given before surgery

Topics

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

Medical terms in this study, explained in our Lexicon: Neoadjuvant Chemotherapy, Pleural Mesothelioma, Prognosis, Extrapleural Pneumonectomy (EPP), Hemithorax, Metastasis, Overall Survival, Surgical Resection.

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