Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy

Our plain-English summary of Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy, by G. Toyokawa, M. Takenoyama, F. Hirai, et al (International Journal of Clinical Oncology, 2014).

The study

• Authors: G. Toyokawa, M. Takenoyama, F. Hirai, R. Toyozawa, E. Inamasu, M. Kojo, Y. Morodomi, Y. Shiraishi, T. Takenaka, M. Yamaguchi, M. Shimokawa, T. Seto, Y. Ichinose
• Journal: International Journal of Clinical Oncology
• Published: 2014;19(4):601-6
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that responds poorly to chemotherapy. Although treatment with pemetrexed in combination with cisplatin serves as first-line chemotherapy for MPM, the optimal second-line and beyond therapy has not yet been fully examined.

Methods: Between March 2008 and October 2011, 17 consecutive Japanese patients pretreated with at least one regimen of platinum plus pemetrexed chemotherapy received gemcitabine and vinorelbine. Responses, survival time, and toxicity were retrospectively evaluated.

Results: Response [partial response (PR) + complete response (CR)] and disease control [stable disease (SD) + PR + CR] rates were 18 and 82 %, respectively. The median progression-free survival (PFS) after combination chemotherapy was 6.0 months, whereas the median overall survival (OS) was 11.2 months. Grade 3 or 4 neutropenia and anemia were observed in 41 and 29 % of patients, respectively, and one patient experienced febrile neutropenia. Grade 3 or 4 nonhematologic toxicities included constipation (6 %) and phlebitis (6 %).

Conclusion: Combination chemotherapy using gemcitabine with vinorelbine was shown to have moderate activity in Japanese MPM patients pretreated with platinum plus pemetrexed chemotherapy. A further multicenter phase II trial is warranted to confirm the efficacy and safety of this combination treatment.

In plain English

This was a retrospective study at the National Kyushu Cancer Center, Japan. The authors reviewed the records of 17 consecutive Japanese patients with malignant pleural mesothelioma, treated between March 2008 and October 2011, whose disease could not be removed by surgery or had returned after it. All had first received platinum plus pemetrexed, then gemcitabine with vinorelbine. Asbestos exposure was known in 11 of the 17 (65%). Three patients (18%; 95% confidence interval 3.8 to 43.4%) had a partial response, 11 (64%; 95% CI 38.3 to 85.8%) had stable disease, and in 3 (18%; 95% CI 3.8 to 43.4%) the disease progressed. None had a complete response. Median progression-free survival after starting the combination was 6.0 months, and median overall survival was 11.2 months. Severe (grade 3 or 4) neutropenia, a drop in a type of white blood cell, occurred in 41% of patients and anemia in 29%. There were no treatment-related deaths. The authors concluded the combination showed moderate activity with manageable toxicities and that a multicenter phase II trial is needed. They noted the study was retrospective, small and single-institution.

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 medical records (single-institution case series of treated patients)
• Who was studied: 17 consecutive Japanese patients with malignant pleural mesothelioma (out of 27 MPM patients seen) at National Kyushu Cancer Center, Fukuoka, Japan, treated March 2008 through October 2011. All had nonresectable disease or recurrence after surgery and had been pretreated with platinum plus pemetrexed. Median age was 58 (range 41 to 75), and 15 of 17 (88%) were men. 14 received the combination as second-line treatment and 3 as third-line or beyond.
• Exposure: The treatment studied was gemcitabine 1000 mg/m2 plus vinorelbine 25 mg/m2 on days 1 and 8 every 3 weeks. Asbestos exposure status of patients: yes in 11 (65%), no in 1 (6%), unknown in 5 (29%). No fiber types were reported.
• Main results:
  • Of the 17 patients, 3 (18%; 95% CI 3.8 to 43.4%) had a partial response, 11 (64%; 95% CI 38.3 to 85.8%) had stable disease and 3 (18%; 95% CI 3.8 to 43.4%) had progressive disease. No complete response was seen. The response rate was 18% and the disease control rate 82%.
  • Median progression-free survival after the combination was 6.0 months. The 1-year progression-free survival rate was 17.6% (95% CI 0.0 to 35.6%).
  • Median overall survival after the combination was 11.2 months. The 1-year overall survival rate was 43.9% (95% CI 19.6 to 68.2%).
  • Grade 3 or 4 anemia, leucopenia and neutropenia occurred in 29%, 24% and 41% of patients. Grade 3 or 4 constipation (6%) and phlebitis (6%) occurred. One patient had febrile neutropenia, and there were no treatment-related deaths.
  • Dose reductions were made in 38 of the 106 cycles given (35%). Median number of cycles was five (range one to 19).
  • Median progression-free survival differed by sex (men 3.0 vs women 14.5 months, P = 0.015; only 2 women), by stage (stage I to III 8.8 vs stage IV 2.4 months, P = 0.032) and by response to first-line chemotherapy (stable disease or partial response 6.8 vs progressive disease 1.6 months, P = 0.012). No variable had a significant impact on overall survival.
• The authors' conclusion: The authors concluded that gemcitabine with vinorelbine showed moderate activity with manageable toxicities in relapsed Japanese patients with MPM after failure of platinum with pemetrexed, and that a multicenter phase II trial is needed.
• Limitations the authors state:
  • The study was retrospective, small (17 patients) and from a single institute.
  • Multivariate analysis could not be performed because there were too few patients.
  • Metabolic response by PET/CT was not assessed.

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: Gemcitabine, Vinorelbine, Pleural Mesothelioma, Pemetrexed (Alimta), Chemotherapy, Neoplasm, Cisplatin, Progression-Free Survival.

Related studies

• Successful salvage chemotherapy with gemcitabine and vinorelbine in a malignant pleural mesothelioma patient previously treated with pemetrexed — T. Agatsuma, T. Koizumi, et al. (2010)
• Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma — M.G. Zauderer, S.L. Kass, et al. (2014)
• Second-line gemcitabine-based chemotherapy regimens improve overall 3-year survival rate in patients with malignant pleural mesothelioma: a multicenter retrospective study — H. Mutlu, S. Gündüz, et al. (2014)
• Vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma — P.A. Zucali, M. Perrino, et al. (2014)
• Comparison of cisplatin plus pemetrexed and cisplatin plus gemcitabine for the treatment of malignant pleural mesothelioma in Japanese patients — T. Shukuya, T. Takahashi, et al. (2014)
• A dose-finding study of gemcitabine and vinorelbine in advanced previously treated malignancies — J.P. Delord, E. Raymond, et al. (2000)

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