Can pemetrexed help in malignant mesothelioma?

Our plain-English summary of Can pemetrexed help in malignant mesothelioma? (Drug and Therapeutics Bulletin, 2006).

The study

• Journal: Drug and Therapeutics Bulletin
• Published: 2006;44(10):77-80
• Type of article: Review
• Read it: PubMed · Publisher

Abstract

Mesothelioma is a cancer that originates in the pleura or, more rarely, the peritoneum, and is almost always due to exposure to asbestos fibres. It is typically fatal, with a median survival of about 8-14 months after diagnosis. Conventional treatment options have not improved this poor outlook. Also, the number of deaths attributable to malignant mesothelioma has been rising rapidly in the UK since the late 1960s, and is set to peak at about 1,950-2,450 per year between 2011 and 2015. It is against this background that pemetrexed (pronounced pe-me-treks-ed) (Alimta - Lilly) has recently become available for use with cisplatin for the treatment of patients with unresectable malignant pleural mesothelioma who have not previously been treated with chemotherapy. Currently, this is the only chemotherapy regimen licensed for patients with malignant pleural mesothelioma in the UK. Here we review the care of patients with malignant pleural mesothelioma, focusing on what, if anything, pemetrexed might offer such individuals.

In plain English

This was a review article in a UK drug bulletin, not an original study. It looked at the care of patients with malignant pleural mesothelioma, a cancer the article describes as almost always due to exposure to asbestos fibres. It focused on what the drug pemetrexed, given with cisplatin, might offer. The review relied mainly on one single-blind randomised trial by other researchers in 456 patients who had not had chemotherapy before. In that trial, median survival was 12.1 months with pemetrexed plus cisplatin versus 9.3 months with cisplatin alone. At one year, 50.3% versus 38.0% were alive. Three treatment-related deaths occurred among the first 43 patients on the combination, before folic acid and vitamin B12 supplements were added. Grade 3 or 4 neutropenia, a serious blood side effect, affected 27.9% on the combination versus 2.3% on cisplatin alone. The authors noted that it was unclear how the combination compares with active symptom control. They also noted that the quality-of-life results were published only in abstract form. They concluded that, although pemetrexed is expensive, offering it is reasonable.

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 (drug bulletin article reviewing care of malignant pleural mesothelioma and the evidence on pemetrexed)
• Who was studied: Patients with malignant pleural mesothelioma. The main trial reviewed (not conducted by the authors) included 456 patients not previously treated with chemotherapy.
• Exposure: Not an asbestos exposure study. The treatment reviewed was pemetrexed plus cisplatin. The article states mesothelioma is almost always due to asbestos fibres but names no fiber types.
• Main results:
  • In the reviewed randomised trial, median survival was 12.1 months in the pemetrexed plus cisplatin group versus 9.3 months in the cisplatin-only group (p=0.02).
  • In the reviewed trial, median time to progression was 5.7 months with the combination versus 3.9 months with cisplatin alone (p=0.001).
  • In the reviewed trial, 50.3% of the combination group were alive at 1 year versus 38.0% of the cisplatin-alone group (p=0.012).
  • In the reviewed trial, three treatment-related deaths (7%) occurred among the first 43 patients in the pemetrexed group. After that, patients were also given folic acid and vitamin B12 supplements.
  • In the reviewed trial, grade 3 or 4 neutropenia occurred in 27.9% of the combination group versus 2.3% of the cisplatin-alone group (p less than 0.001).
  • Within the combination group, grade 3 or 4 neutropenia occurred in 41.4% of patients never or partially given vitamin supplements versus 23.3% of those fully supplemented (p=0.011).
  • Quality-of-life results from the reviewed trial were published only as an abstract. At week 18, the combination group appeared to fare better on global quality of life (p=0.012).
  • One 500mg vial cost £800. The article estimated six treatment cycles at £9,600. NICE's Final Appraisal Determination did not recommend the drug except in clinical trials, and that judgement was being appealed.
• The authors' conclusion: The authors concluded that, despite its cost, offering pemetrexed is reasonable given the difference it can make to the poor outlook of the disease. They based this on one single-blind randomised trial suggesting nearly 3 months longer survival than with cisplatin alone.
• Limitations the authors state:
  • It is unclear how pemetrexed plus cisplatin compares with active symptom control.
  • The quality-of-life results from the trial had been published only in abstract form.
  • Pemetrexed is expensive, and providing it would become increasingly costly as cases rise.

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), Malignant Mesothelioma, Mesothelioma, Pleura, Peritoneum, Median Survival, Cisplatin, Unresectable.

Related studies

• Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali, et al. (2011)
• Molecular resistance fingerprint of pemetrexed and platinum in a long-term survivor of mesothelioma — O.D. Røe, A. Szulkin, et al. (2012)
• Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany — M. Reck, R.A. Stahel, et al. (2010)
• New tricks for old biomarkers: thymidylate synthase expression as a predictor of pemetrexed activity in malignant mesothelioma — P.A. Zucali, E. Giovannetti, et al. (2010)
• Pemetrexed in malignant pleural mesothelioma and the clinical outcome — A. Knuuttila, E.R. Salomaa, et al. (2012)
• Pemetrexed for malignant pleural mesothelioma: Is it a standard second-line therapy? — K. Tamura, Y. Fujiwara (2010)

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