Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy

Our plain-English summary of Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy, by M.D. Saint-Pierre, C. Pease, H. Mithoowani, et al (Lung Cancer International, 2015).

The study

• Authors: M.D. Saint-Pierre, C. Pease, H. Mithoowani, T. Zhang, G.A. Nicholas, S.A. Laurie, P. Wheatley-Price
• Journal: Lung Cancer International
• Published: 2015;2015:590148
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction. Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P = 0.35). Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P = 0.97). Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.

In plain English

This retrospective review of records at The Ottawa Hospital in Canada covered 245 patients with pathology-proven malignant pleural mesothelioma diagnosed between January 1991 and June 2012. The authors asked whether survival changed after pemetrexed, a folate antimetabolite drug often paired with platinum chemotherapy, was approved in Canada on May 21, 2004. About half the patients (123 of 245) had a known asbestos exposure. Fiber types were not reported. Median overall survival for all patients was 9.4 months (95% confidence interval 7.8 to 12.0). Among the 139 patients given chemotherapy, those diagnosed before approval (72) had a median survival of 14.2 months and those diagnosed after (67) had 13.2 months (P = 0.35). The 52 patients given platinum with pemetrexed had a median of 14.1 months, against 13.6 months for other regimens (P = 0.97). Receiving any chemotherapy was associated with longer survival. Performance status, tissue type and stage were independently associated with survival. The authors concluded that their review did not demonstrate improved survival after folate antimetabolites entered practice. They named the retrospective, single-institution design as a limitation.

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: Retrospective review of patient charts at a single institution, covering 21 years
• Who was studied: 245 patients with pathology-proven malignant pleural mesothelioma identified at The Ottawa Hospital, Ontario, Canada, between January 1991 and June 2012. Peritoneal and tunica vaginalis mesothelioma were excluded. 87% were men and the median age was 68.
• Exposure: The main comparison was chemotherapy treatment. Patients treated before the approval of pemetrexed in Canada on May 21, 2004 were compared with those treated after it. Patients given platinum-based chemotherapy with a folate antimetabolite (pemetrexed) were compared with those given other chemotherapy regimens. Asbestos exposure was recorded only as known or not known: 123 of 245 (50.2%) had a known asbestos exposure. No fiber types or doses were reported.
• Main results:
  • Median overall survival for all 245 patients was 9.4 months (95% confidence interval 7.8 to 12.0, Table 3).
  • 139 patients (57%) received at least one course of chemotherapy.
  • Among the 139 chemotherapy patients, median overall survival was 14.2 months for the 72 diagnosed before pemetrexed approval and 13.2 months for the 67 diagnosed after. The authors reported no difference (P = 0.35).
  • The 52 patients who received platinum with pemetrexed had a median overall survival of 14.1 months, compared with 13.6 months for patients on any other chemotherapy regimen (P = 0.97).
  • Receiving any chemotherapy was associated with longer overall survival in both univariate and multivariate analyses. For patients without chemotherapy compared with those who had it, the hazard ratio was 2.32 (95% CI 1.59 to 3.39) (Table 4).
  • Performance status, histology and stage were independently associated with survival. In Table 4, a white blood cell count of 8.7 or more and a platelet count above 400 were also associated with survival.
• The authors' conclusion: The authors concluded that patients who received any chemotherapy survived longer than those who did not. They also concluded that the study did not demonstrate improved survival after folate antimetabolites, specifically pemetrexed, came into clinical practice as a partner to platinum-based chemotherapy.
• Limitations the authors state:
  • Because the study was retrospective, not all data variables were systematically recorded at the time of the clinical encounter.
  • Results came from a single institution, which may limit generalizability.
  • Staging systems varied across the study period, and stage is difficult to determine accurately in mesothelioma.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Chemotherapy, Prognosis, Palliative Care, Asbestos Exposure, Performance Status, Histology, Overall Survival.

Related studies

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• ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment — S. Ponce, S. Cedrés, et al. (2023)
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• Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma — K. Goricar, V. Kovac, et al. (2014)

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