Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma

Our plain-English summary of Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma, by R.E. Favoni, T. Florio (Trends in Pharmacological Sciences, 2011).

The study

• Authors: R.E. Favoni, T. Florio
• Journal: Trends in Pharmacological Sciences
• Published: 2011;32(8):463-79
• Type of article: Review
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Human malignant pleural mesothelioma (hMPM) is an aggressive asbestos-associated cancer, the incidence of which is increasing and which, despite progress in diagnosis and therapy, continues to have a poor prognosis. Asbestos fibers induce aberrant cell signaling, leading to proto-oncogene activation and chemoresistance. In this review, we discuss the evolution of pharmacological management of hMPM up to the most recent advances. Monotherapy with single cytotoxic drugs achieves modest objective response rates, seldom reaching 30%. However, combination regimens using novel drugs and standard molecules are showing gradually improving responses and clinical benefits. Phase II/III studies have identified pemetrexed, a multitarget folate pathway inhibitor in combination with platinum derivatives, and the cisplatin/gemcitabine association as front-line chemotherapy for hMPM. Detailed knowledge of molecular mechanisms of signal transduction and neoangiogenesis in hMPM should aid in the design and screening of other promising compounds such as more efficacious receptor tyrosine kinase inhibitors.

Copyright © 2011 Elsevier Ltd. All rights reserved.

In plain English

This article was a review, not a new study. The authors, from Genoa, Italy, described human malignant pleural mesothelioma as an asbestos-associated cancer. They discussed how drug treatment of the disease had developed, drawing on laboratory studies in mesothelioma cell lines and mice and on published clinical trials of single drugs and drug combinations. They wrote that drugs used over past decades had shown poor response rates, often no higher than 20%. They reported that two randomized phase III trials found that cisplatin combined with pemetrexed or raltitrexed gave better responses than cisplatin alone. Targeted drugs such as gefitinib, erlotinib and imatinib showed modest effect when used alone. In one multicenter trial cited in the review, 75 patients had cisplatin and pemetrexed before surgery and radiation. The response rate was 29.3%, and median overall survival was 16.6 months. The authors concluded that pemetrexed and raltitrexed are active and highly synergistic with platinum drugs, but that response rates remain modest and more research is needed. They noted that the rarity of the disease and small trials may contribute to poor results.

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 preclinical studies and clinical trials of drug treatment for human malignant pleural mesothelioma
• Who was studied: Published studies on human malignant pleural mesothelioma: laboratory studies in cell lines and animal models, and phase I to III clinical trials in patients (summarized in tables)
• Exposure: Not an asbestos-exposure study. The exposures reviewed were drug treatments: standard cytotoxic chemotherapy alone and in combination (for example cisplatin with pemetrexed or raltitrexed) and targeted drugs (tyrosine kinase, mTOR, proteasome and HDAC inhibitors). The authors' introduction describes the disease as asbestos-associated.
• Main results:
  • The authors wrote that drugs used over past decades had shown poor response rates, often no higher than 20%.
  • Two randomized phase III trials cited by the review found that cisplatin combined with pemetrexed or raltitrexed gave better responses than cisplatin alone.
  • Targeted drugs aimed at EGFR (gefitinib, erlotinib), PDGFR-beta (imatinib) or VEGF (bevacizumab) showed modest efficacy when used as single agents in the trials reviewed.
  • In a cited multicenter neoadjuvant trial of 75 patients, four cycles of cisplatin-pemetrexed followed by extrapleural pneumonectomy and radiation gave a 29.3% response rate and a median overall survival of 16.6 months.
  • In a cited phase II study of 50 patients, sorafenib achieved partial response in 6% and stable disease in 54%.
  • In a cited laboratory study in MSTO-211H mesothelioma cells, giving pemetrexed before gemcitabine was strongly synergistic, while simultaneous exposure was antagonistic.
• The authors' conclusion: The authors concluded that the new-generation folate inhibitors pemetrexed and raltitrexed are active as single agents and highly synergistic with platinum drugs. They added that absolute response rates remain modest compared with other tumor types and that further research is needed.
• Limitations the authors state:
  • The authors described only a representative selection of the preclinical studies.
  • The authors noted that the rarity of the disease, the small size of clinical trials, patient heterogeneity and subtypes with different treatment sensitivity may contribute to the poor chemotherapy results.

Topics

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

Medical terms in this study, explained in our Lexicon: Chemotherapy, Pleural Mesothelioma, Prognosis, Pemetrexed (Alimta), Cisplatin, Gemcitabine, Tyrosine Kinase Inhibitor.

Related studies

• Chemotherapy and targeted therapies for unresectable malignant mesothelioma — R.J. Kelly, E. Sharon, et al. (2011)
• Combined FDG-PET/CT in response evaluation of malignant pleural mesothelioma — P. Veit-Haibach, N.G. Schaefer, et al. (2010)
• The role of pemetrexed combined with targeted agents for non-small cell lung cancer — K. Konopa, J. Jassem (2010)
• Chemotherapy management of malignant pleural mesothelioma: a phase II study comparing two popular chemotherapy regimens — E.E. Habib, E.S. Fahmy (2013)
• Continued pemetrexed and platin-based chemotherapy in patients with malignant pleural mesothelioma (MPM): value of 18F-FDG-PET/CT — N.G. Schaefer, P. Veit-Haibach, et al. (2012)
• Targeted therapies in malignant pleural mesothelioma: a review of clinical studies — L. Greillier, S. Marco, et al. (2011)

Browse return to medical research.