Chemotherapy of malignant pleural mesothelioma

Our plain-English summary of Chemotherapy of malignant pleural mesothelioma, by P. Bertino, M. Carbone, H. Pass (Expert Opinion on Pharmacotherapy, 2009).

The study

• Authors: P. Bertino, M. Carbone, H. Pass
• Journal: Expert Opinion on Pharmacotherapy
• Published: 2009;10(1):99-107
• Type of article: Review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Owing to worldwide use of asbestos during the past century, the global incidence of mesothelioma is still increasing. Although the outcome for patients remains poor, there has been definite progress in the systemic treatment of this disease within the past 5 years.

Objective: By examining the clinical trials performed and the role of novel emerging agents, this review aims to provide an 'expert opinion' on evidences that validate chemotherapy as current 'standard of care' for inoperable mesothelioma.

Methods: Relevant literature about clinical trials was reviewed using a PubMed search and other relevant data about novel therapeutic approaches both established and in development.

Conclusion: The response rates achieved using chemotherapeutic treatments are higher than previous ones, and in the future may be improved by the use of combined and personalized therapies.

In plain English

This article was a review, not an original study. The authors searched PubMed for clinical trials of chemotherapy for malignant pleural mesothelioma and summarized them, along with newer drugs in development. It did not study asbestos exposure. In a Phase III trial of 448 patients by Vogelzang and colleagues, median survival was 12.1 months with pemetrexed plus cisplatin versus 9.3 months with cisplatin alone. In a 250-patient trial, response rates were 23.6% with raltitrexed plus cisplatin versus 13.6% with cisplatin alone, which the review called nonsignificant. A cited meta-analysis of 59 trials found higher response rates with platinum-containing regimens. A Phase III trial of second-line pemetrexed did not significantly increase overall survival. In a trimodality series of 183 patients, a selected subgroup of 31 had median survival of 51 months. In the authors' own laboratory tests, three mesothelioma cell lines showed very different lethal concentrations (LC50) for gemcitabine and pemetrexed. The authors concluded that chemotherapy seemed to offer a modest survival benefit, and that whether this outweighs its side effects is a matter of personal choice.

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 clinical trials, with a brief report of the authors' own laboratory cell-line tests
• Who was studied: Published clinical trials of chemotherapy in malignant (mainly pleural) mesothelioma, identified through a PubMed search. The review does not state the number of studies reviewed or the search dates.
• Exposure: Not an asbestos exposure study. The 'exposures' were chemotherapy drugs given singly or in combination (pemetrexed, cisplatin, raltitrexed, carboplatin, gemcitabine, vinorelbine and others), including combinations with surgery and radiation, plus newer targeted drugs
• Main results:
  • Vogelzang trial (448 patients, cited by the review): median survival was 12.1 months in the pemetrexed/cisplatin arm versus 9.3 months in the cisplatin-alone arm (p = 0.020). Response rates were 41.3% versus 16.7%.
  • EORTC trial (250 patients, cited by the review): response rate was 23.6% with raltitrexed plus cisplatin versus 13.6% with cisplatin alone (p = 0.056), described as a nonsignificant improvement. Median survival was 11.4 versus 8.8 months.
  • A cited meta-analysis of 59 published trials found response rates of 23.2% for platinum-containing regimens versus 11.6% for nonplatinum-containing regimens (p < 0.001).
  • Cited Phase III second-line trial (243 previously treated patients): pemetrexed plus best supportive care raised the response rate (18.7% versus 1.7%) compared with best supportive care alone, but overall survival was not increased significantly.
  • Cited O'Brien trial (43 symptomatically stable patients): median survival was 14 months with early chemotherapy versus 10 months with delayed chemotherapy (p = 0.1).
  • Cited Sugarbaker trimodality series (183 patients with early-stage disease): median overall survival was 19 months. In a subgroup of 31 patients with epithelial histology, negative margins and no extrapleural nodal involvement, median survival was 51 months.
  • In the authors' own viability tests, three mesothelioma cell lines showed very different lethal concentrations (LC50) for gemcitabine and pemetrexed.
• The authors' conclusion: The authors concluded that there seems to be a modest survival benefit from chemotherapy in mesothelioma patients. In their view, whether this benefit outweighs the side effects is a matter of personal choice, and cost is a further consideration.
• Limitations the authors state:
  • The authors stated that there is no randomized-trial evidence that routine trimodality therapy benefits all mesothelioma patients.
  • The authors stated that the reviewed trials often do not show the palliative benefit of chemotherapy for an individual patient.

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, Mesothelioma, Clinical Trial.

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