Biology and management of malignant pleural mesothelioma

Our plain-English summary of Biology and management of malignant pleural mesothelioma, by P.A. Zucali, G. Giaccone (European Journal of Cancer, 2006).

The study

• Authors: P.A. Zucali, G. Giaccone
• Journal: European Journal of Cancer
• Published: 2006;42(16):2706-14
• Type of article: Review
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is an aggressive tumour, with a poor prognosis and an increasing incidence as a result of widespread exposure to asbestos. The results of the treatments available are poor. Surgery and radiotherapy have a limited role in highly selected patients and systemic therapy is the only potential treatment option for the majority of patients. Despite some definite activity of the novel antifolates such as pemetrexed and raltitrexed, the results, even in combination with platinating agents, are still modest, with a median survival of approximately one year. The better understanding of the biology of mesothelioma makes the assessment of a number of targeted agents particularly interesting. Unfortunately, the targeted agents imatinib, gefitinib, erlotinib and thalidomide have been shown to be ineffective in unselected patients. Studies with anti-angiogenesis agents are ongoing. An improvement of the knowledge of major molecular pathways involved in malignant mesothelioma is needed in order to define proper targets for the systemic treatment of this disease.

In plain English

This article was a review, not a new study. The authors summarized published research on the biology and treatment of malignant pleural mesothelioma. On biology, they wrote that the disease is linked to amphibole fibres with a high length-to-diameter ratio: crocidolite, amosite and tremolite. On treatment, they described earlier randomised trials. In one, adding pemetrexed to cisplatin raised median survival from 9.3 to 12.1 months compared with cisplatin alone, a difference the authors reported as statistically significant. In another, adding raltitrexed gave a 2.6-month increase that had borderline significance. They reported that earlier studies of the targeted drugs imatinib, gefitinib and erlotinib showed limited or no activity in these patients. They gave the operative mortality of extrapleural pneumonectomy as 5 to 9%. Citing one study, they reported that certain subgroups given combined treatment including surgery had a median survival approaching 5 years. They noted that the evidence on surgery and radiotherapy is hard to interpret, partly because of a lack of randomised trials. The authors concluded that the results of available treatments are still modest.

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 research
• Who was studied: Published laboratory, animal and clinical research on the biology and management of patients with malignant pleural mesothelioma; no new patients were studied
• Exposure: The review states that mesothelioma development is linked to amphibole fibres with a high length-to-diameter ratio (crocidolite, amosite and tremolite); the review's main subject is treatment rather than exposure
• Main results:
  • Reported from an earlier randomised trial: in patients given pemetrexed plus cisplatin, median survival was 12.1 months versus 9.3 months with cisplatin alone, and the difference was statistically significant. In a separate raltitrexed trial, the survival increase was 2.6 months and of borderline significance.
  • The pemetrexed survival difference was statistically significant, unlike the raltitrexed result
  • Reported from earlier studies: imatinib, gefitinib and erlotinib showed limited or no activity in patients with malignant pleural mesothelioma
  • Reported from earlier work: PTK787, an anti-angiogenesis drug, showed modest activity with a response rate of 6%
  • The authors gave the operative mortality of extrapleural pneumonectomy as 5 to 9%
  • Reported from one cited study: patients with epithelial cell type, no extra-pleural nodal involvement and negative surgical margins who received combined-modality treatment had a median survival approaching 5 years
  • Reported from phase II trials in previously treated patients: partial responses to second-line agents ranged from 5% to 10%
• The authors' conclusion: The authors concluded that some progress had come from cisplatin combined with an antifolate, but that the results of available treatments are still modest. They added that better knowledge of the molecular changes specific to mesothelioma is needed to develop targeted drugs.
• Limitations the authors state:
  • The authors state that the evidence on surgery and radiotherapy is difficult to interpret because of variable patient selection, small numbers of patients and the lack of randomised trials
  • The authors state that post-study chemotherapy in the pemetrexed trial was not randomised, so it cannot be known whether it caused the longer survival

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, Mesothelioma, Prognosis, Systemic Therapy, Antifolate, Pemetrexed (Alimta), Raltitrexed, Median Overall Survival.

Related studies

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• Surgical biology for the clinician: peritoneal mesothelioma: current understanding and management — T.C. Chua, T.D. Yan, et al. (2009)
• Future developments in the management of malignant pleural mesothelioma — P.A. Zucali, F. De Vincenzo, et al. (2009)
• Advances in the biology of malignant pleural mesothelioma — P.A. Zucali, G.L. Ceresoli, et al. (2011)
• Summary of presentations from the 46th Annual Meeting of the American Society of Clinical Oncology (2010) focus on tumor biology and biomarkers related to lung cancer — J. Subramanian, L. Corrales, et al. (2011)
• Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience — M. Ried, T. Potzger, et al. (2013)

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