Vinca alkaloids in the therapeutic management of malignant pleural mesothelioma

Our plain-English summary of Vinca alkaloids in the therapeutic management of malignant pleural mesothelioma, by G.L. Ceresoli, P.A. Zucali (Cancer Treatment Reviews, 2015).

The study

• Authors: G.L. Ceresoli, P.A. Zucali
• Journal: Cancer Treatment Reviews
• Published: 2015;41(10):853-8
• Type of article: Review
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Therapeutic options for malignant pleural mesothelioma (MPM) are limited. Most patients are treated with chemotherapy during the course of their disease. The combination of pemetrexed with a platinum compound is the standard of care in the first-line setting, while no established treatment exists in the second and beyond-line setting. Vinca alkaloids are chemotherapeutic agents that have demonstrated clinical efficacy both as single agents and in combination in a broad spectrum of cancers, including MPM. Vinorelbine has shown activity in MPM patients as neoadjuvant therapy, first-line treatment, and in the second and third-line setting. Vinflunine is a derivative of vinorelbine that has been studied in MPM as first-line agent. While the role of vinca alkaloids in the first-line treatment of MPM seems marginal, treatment with vinorelbine remains a reasonable option for pemetrexed-pretreated patients in clinical practice, based on an acceptable rate of stable disease, confirmed by several trials. Ongoing studies on predictive biomarkers for vinorelbine will hopefully be able to individualize treatment, increasing response rates and survival outcomes.

Copyright © 2015 Elsevier Ltd. All rights reserved.

In plain English

This 2015 article is a review, not a new study. The authors searched PubMed, Cancerlit, reference lists and congress abstracts for studies of two vinca alkaloid drugs, vinorelbine and its derivative vinflunine, in malignant pleural mesothelioma. They grouped the studies into first-line treatment, second-line and later treatment, and tests that might predict response. In the reviewed MS01 trial, a final analysis of 409 patients showed a small, non-significant survival benefit for chemotherapy plus active symptom control over symptom control alone. The authors put second-line response rates at 0% to 16%, with 43–84% of patients achieving disease control, though one reviewed gemcitabine-plus-vinorelbine study reported 18% partial responses. The authors judged toxicity generally mild. They judged that adding gemcitabine to vinorelbine did not seem to offer an advantage over vinorelbine alone, and called the first-line role of vinca alkaloids marginal. The authors concluded that the acceptable rate of stable disease warrants using vinorelbine in patients already treated with pemetrexed, though it likely has small or no impact on survival. They noted the studies were often small and differed in patients, schedules and designs.

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: Literature review of published studies, congress abstracts and ongoing trials on vinorelbine and vinflunine in malignant pleural mesothelioma
• Who was studied: Published clinical trials and retrospective series of patients with malignant pleural mesothelioma treated with vinorelbine or vinflunine, grouped by first-line treatment, second-line and later treatment, and pharmacogenomic (predictive biomarker) analyses. No search dates are given.
• Exposure: Treatment with vinca alkaloid chemotherapy, mainly vinorelbine (given alone or with cisplatin, carboplatin, oxaliplatin or gemcitabine), and vinflunine. The article does not study asbestos exposure.
• Main results:
  • In the reviewed MS01 phase III trial, the final analysis of 409 patients showed a small, non-significant survival benefit for active symptom control plus chemotherapy compared with active symptom control alone
  • In their discussion, the authors stated that response rates in the available second-line studies ranged from 0% to 16%, and that 43–84% of patients achieved disease control
  • One reviewed second-line study of gemcitabine plus vinorelbine (Toyokawa et al., 17 patients pretreated with pemetrexed plus platinum) reported a partial response rate of 18% and a disease control rate of 82%, above the 0% to 16% range the authors gave
  • In the reviewed multicenter phase II study of first-line vinflunine (67 patients enrolled, 5 not evaluable for response), the response rate was 14% and stable disease was seen in 56%
  • In reviewed biomarker work on tumor samples from patients treated with cisplatin plus vinorelbine (50 with tissue available), a combined ERCC1/TUBB3 biomarker profile was significantly associated with progression-free survival (HR 6.45, p = 0.002) and overall survival (HR 4.64, p = 0.006) in multivariate analysis
  • The authors judged toxicity to be generally mild across the studies reviewed
  • The authors judged that adding gemcitabine to vinorelbine did not seem to offer an advantage over single-agent vinorelbine, at the cost of more toxicity
  • The authors described the role of vinca alkaloids in first-line treatment as marginal
• The authors' conclusion: The authors concluded that the acceptable rate of stable disease warrants the use of vinorelbine in patients already treated with pemetrexed, though it likely has small or no impact on survival
• Limitations the authors state:
  • Comparing results across studies is difficult because patient selection, treatment schedules and study designs differ
  • Published studies often have serious limitations because they include small numbers of patients and mixed patient groups

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: Pleural Mesothelioma, Chemotherapy, Pemetrexed (Alimta), Vinorelbine, Neoadjuvant Therapy, Biomarker.

Related studies

• Vinflunine: review of a new vinca alkaloid and its potential role in oncology — J.S. Ng (2011)
• Chemotherapy management of malignant pleural mesothelioma: a phase II study comparing two popular chemotherapy regimens — E.E. Habib, E.S. Fahmy (2013)
• Future developments in the management of malignant pleural mesothelioma — P.A. Zucali, F. De Vincenzo, et al. (2009)
• Chemotherapy and targeted therapies for unresectable malignant mesothelioma — R.J. Kelly, E. Sharon, et al. (2011)
• Successful salvage chemotherapy with gemcitabine and vinorelbine in a malignant pleural mesothelioma patient previously treated with pemetrexed — T. Agatsuma, T. Koizumi, et al. (2010)
• Triplet chemotherapy with cisplatin, gemcitabine and vinorelbine for malignant pleural mesothelioma — R. Maruyama, F. Shoji, et al. (2005)

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