Comparison of cisplatin plus pemetrexed and cisplatin plus gemcitabine for the treatment of malignant pleural mesothelioma in Japanese patients

Our plain-English summary of Comparison of cisplatin plus pemetrexed and cisplatin plus gemcitabine for the treatment of malignant pleural mesothelioma in Japanese patients, by T. Shukuya, T. Takahashi, H. Imai, et al (Respiratory Investigation, 2014).

The study

• Authors: T. Shukuya, T. Takahashi, H. Imai, T. Tokito, A. Ono, H. Akamatsu, T. Taira, H. Kenmotsu, T. Naito, H. Murakami, M. Endo, N. Yamamoto
• Journal: Respiratory Investigation
• Published: 2014;52(2):101-6
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Cisplatin plus pemetrexed is a standard front-line chemotherapeutic regimen for inoperable malignant pleural mesothelioma (MPM). However, no clinical trials have compared the efficacy of cisplatin plus pemetrexed and cisplatin plus gemcitabine, which may be comparable based on previous phase II study results. This study aimed at evaluating the efficacy of cisplatin plus pemetrexed and comparing it with that of cisplatin plus gemcitabine in Japanese MPM patients.

Methods: From July 2002 to December 2011, 13 and 17 consecutive patients with inoperable MPM were treated with cisplatin plus gemcitabine and cisplatin plus pemetrexed, respectively, at the Shizuoka Cancer Center. We reviewed the medical charts of these patients and evaluated their characteristics as well as data regarding drug toxicity and antitumor efficacy.

Results: The response rates were 15% and 35% in the cisplatin plus gemcitabine and cisplatin plus pemetrexed groups, respectively (P=0.4069), while disease control rates were 77%, and 82%, respectively (P=0.9999). Progression-free survival was significantly higher with cisplatin plus pemetrexed (median, 215.5 days) than with cisplatin plus gemcitabine (median, 142.5 days) (P=0.0146; hazard ratio [HR], 0.3552). Overall survival showed a tendency towards being superior with cisplatin plus pemetrexed (median, 597.5 days) compared with cisplatin plus gemcitabine (median, 306.5 days) (P=0.1725, HR, 0.5516). Hematological toxicities, especially thrombocytopenia and neutropenia, tended to be more frequent and severe in the cisplatin plus gemcitabine group.

Conclusions: Cisplatin plus pemetrexed may be superior and should continue to be the standard front-line chemotherapeutic regimen for inoperable MPM.

© 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

In plain English

This retrospective chart review at the Shizuoka Cancer Center in Japan compared two first-line chemotherapy combinations in patients with inoperable malignant pleural mesothelioma treated between July 2002 and December 2011. Thirteen patients received cisplatin plus gemcitabine and 17 received cisplatin plus pemetrexed. Definite asbestos exposure was recorded in 4 of 13 and 9 of 17, respectively. Response rates were 15% with gemcitabine and 35% with pemetrexed, a difference that was not statistically significant. Median progression-free survival was 142.5 days with gemcitabine and 215.5 days with pemetrexed, a statistically significant difference. Median overall survival was 306.5 and 597.5 days respectively, a difference that was not statistically significant. Blood-related side effects tended to be more frequent and severe with gemcitabine, though not significantly, and there were no treatment-related deaths. The authors concluded that cisplatin plus pemetrexed may be superior and should remain the standard first-line regimen. They noted that the study was small and retrospective, that use of an anti-nausea drug differed between the groups, and that the progression-free survival comparison was not completely reliable.

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 single-centre review of medical charts comparing two chemotherapy regimens
• Who was studied: 30 consecutive patients with inoperable malignant pleural mesothelioma given first-line chemotherapy at the Shizuoka Cancer Center, Japan, between July 2002 and December 2011: 13 given cisplatin plus gemcitabine and 17 given cisplatin plus pemetrexed
• Exposure: The study examined chemotherapy, not asbestos exposure. One group received cisplatin (80 mg/m2) plus gemcitabine (1000 mg/m2, days 1 and 8). The other received cisplatin (75 mg/m2) plus pemetrexed (500 mg/m2, day 1). Both were given every 3 weeks for up to 6 cycles. Definite asbestos exposure was recorded in 4 of 13 patients (31%) in the gemcitabine group and 9 of 17 (53%) in the pemetrexed group.
• Main results:
  • The two groups did not differ significantly in gender, age, tumor histology, performance status, smoking history, asbestos exposure, or tumor stage.
  • Cisplatin plus gemcitabine group: response rate 15% (2 of 13) and disease-control rate 77%.
  • Cisplatin plus pemetrexed group: response rate 35% (6 of 17) and disease-control rate 82%.
  • The differences between the groups in response rate (P = 0.4069) and disease-control rate (P = 0.9999) were not statistically significant.
  • Cisplatin plus gemcitabine group: median progression-free survival 142.5 days and median overall survival 306.5 days.
  • Cisplatin plus pemetrexed group: median progression-free survival 215.5 days and median overall survival 597.5 days.
  • Progression-free survival differed significantly between the groups, favoring cisplatin plus pemetrexed (log-rank P = 0.0146; hazard ratio 0.3552, 95% confidence interval 0.1461 to 0.8422).
  • Overall survival only tended to be better with cisplatin plus pemetrexed, and the difference was not statistically significant (log-rank P = 0.1725; hazard ratio 0.5516, 95% confidence interval 0.2276 to 1.3211).
  • Blood-related side effects tended to be more frequent and severe with cisplatin plus gemcitabine, but the differences were not statistically significant. Grade 3 or worse thrombocytopenia occurred in 38% of the gemcitabine group and 6% of the pemetrexed group (P = 0.0606). Grade 3 or worse neutropenia occurred in 46% and 18% respectively (P = 0.1232).
  • Neither group had any treatment-related deaths.
• The authors' conclusion: The authors concluded that cisplatin plus pemetrexed may be superior and should continue to be the standard first-line chemotherapy for inoperable malignant pleural mesothelioma, and that further studies are needed.
• Limitations the authors state:
  • The study was retrospective and small, which makes a definite conclusion difficult.
  • The small number of patients may have affected the ability to detect statistically significant differences.
  • The severity of non-hematological side effects may have been underestimated because the study was retrospective.
  • Tumor evaluation intervals were less exact than in a prospective study, so the progression-free survival comparison is not completely reliable.
  • The anti-nausea drug aprepitant was used by 11 of the 17 pemetrexed patients and none of the gemcitabine patients. It was not available in Japan until October 2009.
  • Cisplatin plus pemetrexed came into use more recently than cisplatin plus gemcitabine, and the authors noted that outcomes were usually better in the pemetrexed group as a result.

Topics

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

Medical terms in this study, explained in our Lexicon: Cisplatin, Pemetrexed (Alimta), Gemcitabine, Pleural Mesothelioma, Clinical Trial, Progression-Free Survival, Hazard Ratio, Overall Survival.

Related studies

• Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy — G. Toyokawa, M. Takenoyama, et al. (2014)
• Successful salvage chemotherapy with gemcitabine and vinorelbine in a malignant pleural mesothelioma patient previously treated with pemetrexed — T. Agatsuma, T. Koizumi, et al. (2010)
• Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies — H.J. Gray, K. Bell-McGuinn, et al. (2018)
• A feasibility study of induction pemetrexed plus cisplatin followed by pleurectomy/decortication aimed at macroscopic complete resection for malignant pleural mesothelioma — M. Shimokawa, S. Hasegawa, et al. (2013)
• Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study — T. Nakano, K. Kuribayashi, et al. (2021)
• First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma — E. Fujimoto, T. Kijima, et al. (2017)

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