Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study

Our plain-English summary of Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study, by K. Kuribayashi, S. Voss, S. Nishiuma, et al (Lung Cancer, 2012).

The study

• Authors: K. Kuribayashi, S. Voss, S. Nishiuma, K. Arakawa, Y. Nogi, K. Mikami, S. Kudoh
• Journal: Lung Cancer
• Published: 2012;75(3):353-9
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Pemetrexed in combination with cisplatin (Pem/Cis) is the only approved chemotherapeutic regimen for malignant pleural mesothelioma (MPM). At the time of launch, limited safety information was available. The purpose of this postmarketing all-case registry study was to investigate the safety and effectiveness of pemetrexed in patients with MPM.

Methods: From January 2007 to May 2008, MPM patients to be treated with pemetrexed in Japan were registered to this study to monitor its safety and effectiveness. Supply of pemetrexed was restricted to institutions with experienced medical oncologists based on predetermined criteria.

Results: Of 953 patients registered, data from 903 patients were eligible for analysis. Most patients were male, with median age of 65 years and 68.5% had a history of asbestos exposure. More than 90% of patients received the first cycle of Pem/Cis treatment; median number of treatment cycles was 4.0. Treatment-associated death was reported in 0.8% of patients. The incidence of Interstitial lung disease (ILD) associated with Pem/Cis during the observation period was 0.9%. The frequency of ILD in patients with pre-existing asbestosis was higher than that in patients without it. For tumor response, the overall response rate was 25.0% (95% confidence interval (CI): 22.2-28.0%). The six-month survival rate estimated by the Kaplan-Meier method was 75.9%.

Conclusions: This large scale all case registry study appeared to have enrolled a major portion of Japanese MPM patients. Treatment with pemetrexed was generally well tolerated and showed safety and effectiveness comparable to prior clinical trials.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In plain English

This was a prospective, observational postmarketing registry study of the cancer drug pemetrexed, mostly given with cisplatin, in patients with malignant pleural mesothelioma in Japan. Every patient to be treated with pemetrexed from January 2007 to May 2008 had to be registered. Of 953 registered patients, 903 were analyzed. Of these, 68.5% had a history of asbestos exposure, and 8.3% had asbestosis as judged by the prescribing physician. Adverse drug reactions were reported in 84.2% of patients, and seven deaths (0.8%) were possibly associated with the chemotherapy. Interstitial lung disease (ILD) was reported in 0.9% of patients during the observation period and in 1.6% overall. In what the authors called an exploratory analysis, ILD occurred in 5.3% (4/75) of patients with asbestosis versus 1.2% (10/825) without. The adjusted odds ratio was 4.69 (95% CI 1.43 to 15.41). The tumor response rate was 25.0% (95% CI 22.2 to 28.0%), and estimated six-month survival was 75.9%. The authors concluded that pemetrexed was generally well tolerated and showed safety and effectiveness comparable to prior clinical trials.

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: Multicenter, prospective, observational postmarketing surveillance (all-case drug registry) study
• Who was studied: Malignant pleural mesothelioma patients to be treated with pemetrexed in Japan, registered January 2007 to May 2008. 953 were registered and 903 were analyzed. 85.7% were male, the median age was 65 years, and 75 (8.3%) had asbestosis as determined by the prescribing physician.
• Exposure: The exposure studied was treatment with pemetrexed, mostly combined with cisplatin. 619 of 903 patients (68.5%) had a history of asbestos exposure. Fiber types and jobs were not reported.
• Main results:
  • Adverse drug reactions were reported in 84.2% (760) of the 903 analyzed patients.
  • Seven deaths (0.8%) were possibly associated with chemotherapy including pemetrexed.
  • ILD associated with pemetrexed was reported in 0.9% (8/903) of patients during the observation period. Including cases outside that period, it was reported in 1.6% (14/903).
  • In an exploratory analysis, ILD occurred in 5.3% (4/75) of patients with asbestosis and in 1.2% (10/825) of those without.
  • The odds ratio for ILD with asbestosis, adjusted for prior chemotherapy, was 4.69 (95% CI 1.43 to 15.41), which was statistically significant (p = 0.011).
  • The overall tumor response rate among the 903 patients was 25.0% (95% CI 22.2 to 28.0%).
  • Six-month overall survival estimated by the Kaplan-Meier method was 75.9% for all patients and 84.7% (95% CI 81.7 to 87.7%) for the epithelioid subgroup.
• The authors' conclusion: The authors concluded that treatment with pemetrexed was generally well tolerated and showed safety and effectiveness comparable to prior clinical trials.
• Limitations the authors state:
  • Not all newly diagnosed mesothelioma patients in Japan may have been registered.
  • Data quality in postmarketing studies may not match that of clinical trials.
  • There are few postmarketing studies available for comparison.
  • The method used to assess tumor response had a limitation.

Topics

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

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Pleural Mesothelioma, Cisplatin, Asbestos Exposure, Interstitial Lung Disease, confidence interval, Clinical Trial.

Related studies

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• COX-2 specific inhibitors enhance the cytotoxic effects of pemetrexed in mesothelioma cell lines — S.L. O'Kane, G.L. Eagle, et al. (2010)
• Successful salvage chemotherapy with gemcitabine and vinorelbine in a malignant pleural mesothelioma patient previously treated with pemetrexed — T. Agatsuma, T. Koizumi, et al. (2010)
• Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany — M. Reck, R.A. Stahel, et al. (2010)
• The role of pemetrexed combined with targeted agents for non-small cell lung cancer — K. Konopa, J. Jassem (2010)
• Pemetrexed in malignant pleural mesothelioma and the clinical outcome — A. Knuuttila, E.R. Salomaa, et al. (2012)

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