Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma

Our plain-English summary of Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma, by M.G. Zauderer, S.L. Kass, K. Woo, et al (Lung Cancer, 2014).

The study

• Authors: M.G. Zauderer, S.L. Kass, K. Woo, C.S. Sima, M.S. Ginsberg, L.M. Krug
• Journal: Lung Cancer
• Published: 2014;84(3):271-4
• Cited by: 86 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Pemetrexed-cisplatin is the only FDA-approved regimen for malignant pleural mesothelioma (MPM), and the impact on survival is modest. No drugs have been shown to improve survival as second-line therapy, yet vinorelbine and gemcitabine are prescribed based on the results of small phase II trials. To augment the existing limited data, we examined our institutional experience with vinorelbine and gemcitabine in patients with previously treated MPM.

Materials And Methods: We reviewed charts of patients with MPM treated with vinorelbine and/or gemcitabine as second- or third-line therapy between 2003 and 2010. Toxicity was graded according to the Common Terminology Criteria for Adverse Events Version 4.0. CT scans were reviewed with a reference radiologist according to modified RECIST criteria.

Results: Sixty patients were identified: 33 treated with vinorelbine, 15 gemcitabine, and 12 both agents. Eighty-three percent initially received pemetrexed-platinum. Toxicity was substantial: 46% experienced at least one episode of grade 3-4 toxicity. Of 56 patients evaluable radiologically, there was 1 partial response (gemcitabine) giving a response rate of 2% (95% CI: 0-10%). Forty-six percent had stable disease. Median progression free survival was 1.7 months for vinorelbine and 1.6 months for gemcitabine. Median overall survival was 5.4 and 4.9 months, respectively.

Conclusions: Response to second- or third-line vinorelbine or gemcitabine is rare. The high rate of stable disease warrants the continued use of these agents in this setting, though the impact on survival is questionable. These data justify the choice of placebo control arms in randomized trials of novel agents in previously treated patients.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

In plain English

This retrospective review covered Memorial Sloan-Kettering Cancer Center patients with malignant pleural mesothelioma given vinorelbine and/or gemcitabine as second- or third-line chemotherapy in 2003 to 2010. Of 60 patients, 33 received vinorelbine, 15 gemcitabine and 12 both. Forty-six percent had at least one severe (grade 3 to 4) side effect; none died from treatment. Among 56 treatment courses with measurable scans, one partial response gave a response rate of 2% (95% confidence interval 0 to 5%; the abstract says 0 to 10%). The authors also reported stable disease in 46%, without saying of which group. With vinorelbine (45 patients, including 12 given both), median progression-free survival was 1.7 months (95% CI 1.3 to 2.9) and median overall survival 5.4 months (3.8 to 7.4). With gemcitabine (27 patients), these were 1.6 months (1.3 to 3.6) and 4.9 months (3.6 to 8.8). The authors concluded that responses were rare and the impact on survival questionable, but stable disease warranted continued use. They also considered placebo comparison groups reasonable in trials of new second-line treatments. Limitations they noted included retrospective design, unavailable scans and a single center.

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 clinical records at a single institution
• Who was studied: 60 patients with malignant pleural mesothelioma treated at Memorial Sloan-Kettering Cancer Center (New York) between 2003 and 2010: 33 received vinorelbine, 15 gemcitabine, 12 both drugs sequentially; 83% had first received pemetrexed and platinum
• Exposure: Second- or third-line chemotherapy: vinorelbine 25 mg/m2 on days 1 and 8 of a 3-week cycle; gemcitabine 1000 mg/m2 on days 1 and 8 of 21-day cycles or days 1, 8 and 15 of 28-day cycles. The study is about treatment, not asbestos exposure. Asbestos exposure was recorded but not reported in the results.
• Main results:
  • 46% of the 60 patients had at least one episode of grade 3 to 4 toxicity
  • No treatment-related deaths
  • 6 patients (13%) stopped vinorelbine and 7 (26%) stopped gemcitabine because of toxicity
  • Of 72 treatment courses received by the 60 patients, 56 had follow-up imaging
  • Among 56 measurable cases there was one partial response (with gemcitabine), a response rate of 2%. The 95% CI is 0 to 5% in the Results and 0 to 10% in the Abstract.
  • The authors reported a stable disease rate of 46%. The article does not state which group this percentage refers to. The detailed results count both radiographic and clinical stable disease for each drug.
  • Vinorelbine courses: 19 (42%) radiographic stable disease, 4 (8%) clinically stable disease, 20 (43%) radiographic progression, 2 (4%) clinical progression, no responses
  • Vinorelbine group (45 patients, including those who received both drugs): median progression-free survival 1.7 months (95% CI 1.3 to 2.9), median overall survival 5.4 months (95% CI 3.8 to 7.4)
  • Gemcitabine group (27 patients, including those who received both drugs): median progression-free survival 1.6 months (95% CI 1.3 to 3.6), median overall survival 4.9 months (95% CI 3.6 to 8.8)
  • Among the 56 cases, best response to first treatment was not associated with best response to vinorelbine and/or gemcitabine
• The authors' conclusion: The authors concluded that response to second- or third-line vinorelbine or gemcitabine is rare and the impact on survival questionable. They concluded the high rate of stable disease warrants continued use. They also concluded that placebo control arms are reasonable for randomized studies of second-line therapies in malignant pleural mesothelioma.
• Limitations the authors state:
  • Because the study was retrospective, side effects may not have been fully captured
  • Some patients lacked adequate or available imaging for response review
  • A large share of patients (35%) had sarcomatoid or mixed histology, which may have contributed to the low response rate
  • All patients were treated at one tertiary care center, so results may not apply to mesothelioma patients generally

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: Vinorelbine, Gemcitabine, Pleural Mesothelioma, Pemetrexed (Alimta), Cisplatin, Second-Line Therapy, CT Scan, Modified RECIST (mRECIST).

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)
• A dose-finding study of gemcitabine and vinorelbine in advanced previously treated malignancies — J.P. Delord, E. Raymond, et al. (2000)
• Vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma — P.A. Zucali, M. Perrino, et al. (2014)
• A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma — W.S. Lam, J. Creaney, et al. (2020)
• Third-line chemotherapy with carboplatin, gemcitabine and liposomised doxorubicin for malignant pleural mesothelioma — V.A. de Lima, J.B. Sørensen (2015)
• Successful salvage chemotherapy with gemcitabine and vinorelbine in a malignant pleural mesothelioma patient previously treated with pemetrexed — T. Agatsuma, T. Koizumi, et al. (2010)

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