Chemotherapy for malignant pleural mesothelioma: past results and recent developments

Our plain-English summary of Chemotherapy for malignant pleural mesothelioma: past results and recent developments, by S. Tomek, S. Emri, K. Krejcy, et al (British Journal of Cancer, 2003).

The study

• Authors: S. Tomek, S. Emri, K. Krejcy, C. Manegold
• Journal: British Journal of Cancer
• Published: 2003;88(2):167-74
• Type of article: Review
• Cited by: 63 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This review summarises the results of previously conducted clinical trials, and subsequently presents data arising from all phase II-III studies on chemotherapy of malignant pleural mesothelioma (MPM) published since the last relevant overview. While response rates exceeding 30% have barely been achieved with established cytotoxic drugs in MPM therapy, novel chemotherapeutic agents and their combinations appear more promising. This applies especially to the antimetabolites, and in particular to pemetrexed that produced response rates of up to 45% in combination with platinum compounds. Raltitrexed combined with oxaliplatin has also been shown to be effective, and gemcitabine-applied as a single agent or in combination with cisplatin-as well as vinorelbine appear to improve the quality of life in patients presenting with MPM. Data can now be more precisely analysed by increasingly implemented randomised studies, applying a standardised staging system, and distinguishing prognostic groups. While chemotherapy for MPM remains a challenging task, important steps have clearly been made in the past years to combat this aggressive disease. The publication of pemetrexed with cisplatin phase III results in a peer-reviewed journal may soon establish a standard of care.

In plain English

This article was a review of chemotherapy trials for malignant pleural mesothelioma (MPM), covering earlier trials and phase II to III trials published since the last overview; it was not a new study. Established single drugs had shrunk tumours in only 10 to 30% of patients, without significantly affecting median survival. Among newer drugs, pemetrexed with cisplatin produced partial remissions in five of 11 evaluable mesothelioma patients (45%) in a phase I study. A 456-patient phase III trial of pemetrexed plus cisplatin versus cisplatin alone, presented at a May 2002 meeting, favoured the combination for median overall survival, response rate, lung function and quality of life. Raltitrexed with oxaliplatin gave a preliminary 25% response rate (14 of 57 evaluable patients). For gemcitabine with cisplatin, response rates were 47.6% in a 21-patient Australian trial and, in a European trial, four of 22 patients, printed as 15% although that is about 18%. The authors noted few large randomised trials and inconsistent imaging and staging. They concluded that effective chemotherapy finally appeared to exist and that pemetrexed with cisplatin would become a new standard.

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: review of published clinical trials
• Who was studied: Published phase II to III chemotherapy trials in patients with malignant pleural mesothelioma, focusing on those published since the last relevant overview. The summary tables cover trials with more than 15 patients conducted since 1995.
• Exposure: Chemotherapy drugs given alone or in combination, including anthracyclines, platinum compounds, alkylating agents, vinca alkaloids, taxanes and antimetabolites such as pemetrexed, raltitrexed and gemcitabine. Asbestos exposure was not studied.
• Main results:
  • Across earlier trials of single cytotoxic drugs, tumour regression rates were between 10 and 30%, with no significant impact on median survival.
  • For anthracyclines, the overall response rate appeared to be no higher than 15% and median survival did not exceed 8 months.
  • In a Norwegian study, high-dose methotrexate gave a response rate of 37%.
  • In a phase I study of pemetrexed with cisplatin, five of 11 evaluable mesothelioma patients had a partial remission (response rate 45%).
  • In a phase III trial of 456 patients randomised to pemetrexed plus cisplatin or cisplatin alone (results presented at the ASCO meeting in May 2002), the combination gave superior median overall survival, response rate, lung function and quality-of-life measures. The review gives no numbers for this trial.
  • Single-agent pemetrexed in 62 patients gave a response rate of 14.5% and a median survival of 10.7 months.
  • Raltitrexed with oxaliplatin (Institut Gustave Roussy, 70 patients treated) gave a preliminary response rate of 25%, in 14 of 57 patients evaluable for efficacy.
  • In an Australian trial of gemcitabine with cisplatin in 21 patients, the response rate was 47.6% and overall survival was 41 weeks.
  • In a multicentre study of the same gemcitabine and cisplatin regimen in 53 patients, the response rate was 33% and median survival was 11.2 months.
  • In a European multicentre phase II study of gemcitabine with cisplatin, four of 22 assessable patients had a partial response. The article prints this as 15%, but four of 22 is about 18%.
  • Single-agent vinorelbine in 64 patients gave a response rate the article prints as 21% (12 of 64; 12 of 64 is about 19%), with improved quality of life for lung-related symptoms.
• The authors' conclusion: The authors concluded that the data suggest effective chemotherapy finally exists for this disease and that pemetrexed with cisplatin will become a new systemic therapy standard.
• Limitations the authors state:
  • Because MPM is rare, only a few large randomised studies had been carried out.
  • Inadequate imaging and non-uniform staging systems complicated interpretation of trial data.
  • Early trials included mixed groups of patients with different risk factors and were often not powerful enough to assess treatment effects.

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, Clinical Trial, Pemetrexed (Alimta), Raltitrexed, Gemcitabine, Cisplatin, Vinorelbine.

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