Current therapies for malignant pleural mesothelioma

Our plain-English summary of Current therapies for malignant pleural mesothelioma, by T. Nakano (Environmental Health and Preventive Medicine, 2008).

The study

• Author: T. Nakano
• Journal: Environmental Health and Preventive Medicine
• Published: 2008;13(2):75-83
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma is a highly lethal tumor derived from mesothelial cells, and its global incidence is increasing because of widespread exposure of numerous individuals to asbestos in the last 50 years. Mesothelioma is largely untreatable with any of the therapeutic modalities. Recently, a novel multitargeted antifolate pemetrexed has shown promising activity against malignant pleural mesothelioma, producing response rates of up to 40% when used in combination with cisplatin. In a large phase III study, use of a combination of pemetrexed and cisplatin was associated with significantly improved survival time and with greater antitumor activity compared with cisplatin alone. This combination also gave a significant response rate of approximately 50% in patients with epithelioid malignant pleural mesothelioma. These clinical benefits of pemetrexed-cisplatin doublet have changed the perception of mesothelioma chemotherapy. Other combinations, including gemcitabine in combination with cisplatin, have also shown encouraging response rates. Prognosis depends on gender, clinical stage of the tumor, histological subtype, platelet count, leukocyte counts, and performance status. Radiotherapy can palliate mesothelioma patients with chest pain, and has been indicated to be of benefit for the prevention of malignant seeding along the tract of a chest tube or needle biopsy. Trimodality treatment using extrapleural pneumonectomy, radiation and chemotherapy has shown promising therapeutic value. The development of chemotherapeutic regimens and the favorable outcomes of trimodality have led to new combined modality trials. In Japan, multicenter national trials against mesothelioma will begin in the near future.

In plain English

This review described treatments for malignant pleural mesothelioma as of 2007. It summarized other researchers' trials rather than reporting a new study of patients. As background, the author stated that 80% of patients had previous asbestos exposure. Deaths from mesothelioma in Japan rose from 500 in 1995 to 953 in 2004. In a cited international phase III trial, pemetrexed plus cisplatin, given with vitamin B12 and folic acid supplements, produced longer overall survival (12.1 vs. 9.3 months) and a higher response rate (41 vs. 17%) than cisplatin alone. Another cited trial reported median survival of 11.4 vs. 8.8 months for cisplatin plus raltitrexed versus cisplatin alone. The review also covered radiotherapy and surgery. One Boston group treated 176 patients with surgery, chemotherapy and radiation. It reported median survival of 19 months and two- and five-year survival rates of 38 and 14%. The author noted that many chemotherapy trials were small. The author concluded that chemotherapy was starting to show clinical benefit. Pemetrexed–cisplatin, approved in Japan in January 2007, was described as the standard first-line regimen. The author stated there was no standard second-line regimen.

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 treatment studies (not original research)
• Who was studied: No study population of its own. The author discussed published clinical trials in patients with malignant pleural mesothelioma, with background on mesothelioma and asbestos use in Japan.
• Exposure: The review concerns treatments: chemotherapy, radiotherapy, surgery and combined approaches. Asbestos exposure appears only as background: the author states that 80% of patients had previous asbestos exposure.
• Main results:
  • Cited international phase III trial (not this article's own study): patients received pemetrexed plus cisplatin with vitamin B12 and folic acid supplementation, or cisplatin alone. The combination gave overall survival of 12.1 vs. 9.3 months, median time to progression of 5.7 vs. 3.9 months, and a response rate of 41 vs. 17%.
  • The author states that adverse effects of pemetrexed can be minimized with simultaneous folic acid and vitamin B12 supplementation.
  • Cited trial: cisplatin plus raltitrexed improved median survival compared with cisplatin alone (11.4 vs. 8.8 months).
  • Cited evidence: cisplatin alone gives a response rate of 13–14% against malignant pleural mesothelioma.
  • The author states that the pemetrexed–cisplatin combination is the first-line standard medical treatment for malignant pleural mesothelioma.
  • The author states that there is no current standard second-line chemotherapy regimen for malignant pleural mesothelioma.
  • Cited Boston group (trimodality therapy of extrapleural pneumonectomy, chemotherapy and radiotherapy): median survival of 19 months in 176 patients, with two- and five-year survival rates of 38 and 14%.
  • Cited radiotherapy studies: 21 Gy in three fractions was indicated to help prevent tumor seeding along procedure tracts. A randomized study showed no benefit of 10 Gy in a single fraction.
  • Background reported by the author: annual deaths from mesothelioma in Japan rose from 500 in 1995 to 953 in 2004.
• The authors' conclusion: The author concluded that chemotherapy for malignant pleural mesothelioma is starting to have clinical benefit. Pemetrexed–cisplatin, approved in Japan in January 2007, is now the standard first-line regimen, and national multicenter trials in Japan were to begin.
• Limitations the authors state:
  • The author states that many phase II chemotherapy studies were small, single-institution trials with heterogeneous patients, which may lead to statistical bias.
  • The author states that the role of radiotherapy has yet to be fully defined, as many previous studies were small and retrospective.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Mesothelial Cells, Antifolate, Pemetrexed (Alimta), Cisplatin, Epithelioid, Chemotherapy.

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