Malignant mesothelioma: new insights into a rare disease

Our plain-English summary of Malignant mesothelioma: new insights into a rare disease, by J. Remon, P. Lianes, S. Martínez, et al (Cancer Treatment Reviews, 2013).

The study

• Authors: J. Remon, P. Lianes, S. Martínez, M. Velasco, R. Querol, M. Zanui
• Journal: Cancer Treatment Reviews
• Published: 2013;39(6):584-91
• Type of article: Review
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy of the pleura associated with exposure to asbestos. Its incidence is anticipated to increase over the next 10years in both Europe and the developing nations. In advanced disease, chemotherapy is the cornerstone of treatment, especially platinum-containing regimens. Most efforts are directed toward improving standard first-line therapy or developing effective second-line therapy, which is still not yet standardized 10years after the first-line standard of care was established. This review focuses on the systemic management of MPM in patients who are not considered suitable for surgical approaches, and it discusses some questions that remain open such as the benefits of administering a maintenance treatment, whether it is better to give cisplatin or carboplatin as first-line therapy, the role of new drugs as second-line therapy, and the treatment of the elderly population. It also summarizes the results from clinical trials that have evaluated new treatments as first- or second-line therapy, which are based on the understanding of mesothelioma biology, such as antiangiogenic drugs, immunotherapies and growth factors agents.

Copyright © 2012 Elsevier Ltd. All rights reserved.

In plain English

This article was a review of drug treatment for malignant pleural mesothelioma in patients not considered suitable for surgery. Its authors were medical oncologists at Hospital de Mataró in Spain. It was not a study of asbestos exposure, although the authors noted in their introduction that asbestos exposure is the dominant cause of the disease, with a latency period of 20 to 40 years. The review summarized trials by other researchers. In the EMPHACIS trial, adding pemetrexed to cisplatin increased overall survival to 12.1 months, compared with 9.3 months for cisplatin alone. In an EORTC trial, adding raltitrexed to cisplatin gave 11.4 versus 8.8 months. Reviewed trials did not demonstrate a survival benefit from thalidomide maintenance, or an overall survival benefit from second-line pemetrexed or vorinostat. The authors suggested the pemetrexed result may reflect unequal later chemotherapy between groups. The authors concluded that platinum combined with an antifolate drug is the standard of care. They wrote that questions about maintenance, second-line, newer and personalized treatments remain open. They noted that carboplatin substitution was not supported by any randomized trial, and that no randomized trials had shown a survival benefit from second-line regimens.

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: Narrative review of published and conference-reported clinical trials and studies by other researchers
• Who was studied: Patients with malignant pleural mesothelioma not considered suitable for surgery, as studied in the trials reviewed (the review had no patients of its own)
• Exposure: Asbestos exposure was not studied. The review covered drug treatments (chemotherapy and newer drugs). The authors stated as background that asbestos exposure is the dominant cause of the disease.
• Main results:
  • In the EMPHACIS trial (reviewed, not the authors' own), overall survival was 12.1 months with cisplatin plus pemetrexed versus 9.3 months with cisplatin alone (p = 0.02)
  • In the EORTC trial (reviewed), overall survival was 11.4 months with cisplatin plus raltitrexed versus 8.8 months with cisplatin alone (p = 0.048)
  • In the MS01 trial (reviewed), chemotherapy added to active symptom control showed no overall survival benefit compared with active symptom control alone (HR 0.89; 95% CI 0.72 to 1.10; p = 0.29)
  • The NVALT phase III trial (reviewed) included 222 patients and compared thalidomide maintenance with observation. It showed no evidence of benefit in progression-free survival (16 weeks vs. 15 weeks; HR 1.0; 95% CI 0.8 to 1.4; p = 0.83). It also showed no evidence of benefit in overall survival (11 months vs. 13 months; HR 0.78; 95% CI 0.57 to 1.1; p = 0.09).
  • A phase III trial (reviewed) compared second-line pemetrexed with best supportive care in 243 pemetrexed-naive patients. It was negative for its primary end-point, overall survival (8.4 versus 9.7 months; p = 0.74). The authors wrote that this was possibly because of a significant imbalance between arms in chemotherapy given after discontinuation.
  • In a phase III trial (reviewed) of 660 patients who had progressed after pemetrexed and platinum, vorinostat versus placebo did not achieve its overall survival endpoint (31 weeks versus 27 weeks; p = 0.858)
• The authors' conclusion: The authors concluded that platinum combined with an antifolate is the standard of care. They stated that questions about maintenance therapy, second-line treatment, newer drugs and personalized treatment remain unanswered, and that new drugs should be tested in randomized phase II trials.
• Limitations the authors state:
  • The authors stated that results of the two first-line phase III trials should not be extrapolated to insufficiently studied subgroups: patients with moderate or poor performance status, the elderly (over 75), and patients with sarcomatous histology
  • The authors stated that substituting carboplatin for cisplatin is not supported by any randomized clinical trial
  • The authors stated that no randomized trials have shown a survival benefit from second-line regimens

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Pleural Mesothelioma, Pleura, Chemotherapy, First-line Therapy, Second-Line Therapy, Cisplatin, Carboplatin.

Related studies

• Effects of Chrysotile Exposure in Human Bronchial Epithelial Cells: Insights into the Pathogenic Mechanisms of Asbestos-Related Diseases — G.R. Gulino, M. Polimeni, et al. (2016)
• US mesothelioma patterns 1973-2002: indicators of change and insights into background rates — M.J. Teta, P.J. Mink, et al. (2008)
• New insights into understanding the mechanisms, pathogenesis, and management of malignant mesotheliomas — B.T. Mossman, A. Shukla, et al. (2013)
• New insights into the molecular pathogenesis of intrahepatic cholangiocarcinoma — T. Patel (2014)
• The asbestos fibre burden in human lungs: new insights into the chrysotile debate — I.S. Feder, I. Tischoff, et al. (2017)
• Retroperitoneal fibrosis: new insights into clinical presentation and diagnosis — A. Vaglio (2009)

Browse more research in Cancer Treatment Reviews, or return to medical research.