Investigational approaches for mesothelioma

Our plain-English summary of Investigational approaches for mesothelioma, by V.F. Surmont, E.R. van Thiel, K. Vermaelen, et al (Frontiers in Oncology, 2011).

The study

• Authors: V.F. Surmont, E.R. van Thiel, K. Vermaelen, J.P. van Meerbeeck
• Journal: Frontiers in Oncology
• Published: 2011;1:22
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the etiology, epidemiology, natural history, and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. The evidence was collected by a systematic analysis of the literature (2000-2011) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment - INAHTA), NIH database (USA), International Pleural Mesothelioma Program - WHOLIS (WHO Database), with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugs. Currently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients.

In plain English

This article was a review, not a new study. The authors described a systematic search of the medical literature from 2000 to 2011 and summarized standard care and new treatments under investigation for malignant pleural mesothelioma (MPM). Citing two earlier randomized trials, they wrote that combination chemotherapy with cisplatin and an antifolate, either pemetrexed or raltitrexed, was suggested to increase survival compared with cisplatin alone. Median survival improved by 2.6 to 2.8 months in the combination arms. Multicentre phase II trials in highly selected patients with early-stage disease gave chemotherapy, then extrapleural pneumonectomy, then radiotherapy, and reported a median survival of 17 to 20 months. The authors wrote that many biological drugs had been studied but a lot of them seemed to fail. For example, adding bevacizumab to cisplatin and gemcitabine gave a median overall survival of 15.6 versus 14.7 months, a difference that was not statistically significant. The authors concluded that mesothelin-targeted therapies, dendritic cell based immunotherapy and gene therapy held promise and should be explored further. The review was not about asbestos exposure; it noted only that the prognostic value of asbestos exposure is controversial.

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 article based on a systematic analysis of the literature from 2000 to 2011
• Who was studied: Published studies and ongoing trials of treatments for patients with malignant pleural mesothelioma (MPM). The review does not state how many studies it included.
• Exposure: Not an exposure study. The review covered treatments: chemotherapy, surgery, radiotherapy, targeted drugs, immunotherapy, vaccines and gene therapy. Asbestos is mentioned only in a statement about prognosis.
• Main results:
  • Two earlier randomized studies cited by the review suggested that combination chemotherapy including cisplatin and an antifolate, either pemetrexed or raltitrexed, increased survival compared with single-agent cisplatin.
  • In those two cited studies, median survival improved by 2.6 to 2.8 months in the combination chemotherapy arm.
  • Cited multicentre prospective phase II trials tested a multimodality approach in highly selected patients with early-stage mesothelioma. They gave neo-adjuvant chemotherapy, followed by extrapleural pneumonectomy and postoperative radiotherapy, and reported a median survival of 17 to 20 months.
  • In a cited phase III study of second-line pemetrexed versus best supportive care, time to progression was longer with pemetrexed, but overall survival did not improve.
  • The authors wrote that many biologicals had been studied or were under investigation, but a lot of them seemed to fail.
  • In a cited randomized phase II study, median overall survival was 15.6 months with bevacizumab plus chemotherapy versus 14.7 months without bevacizumab. The difference was not statistically significant.
  • In a cited phase II study of the EGFR inhibitor erlotinib in MPM patients, no objective responses were seen.
  • In a cited UK surgical trial (MARS feasibility phase), there was no difference in survival between the treatment arms.
• The authors' conclusion: The authors concluded that, among current investigational drugs, mesothelin-targeted therapies, dendritic cell based immunotherapy and gene therapy hold promise and should be further explored.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Prognosis, Chemotherapy, State-of-the-Art Defense, Etiology, Epidemiology, Clinical Trial.

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