The role of gemcitabine in the treatment of malignant mesothelioma

Our plain-English summary of The role of gemcitabine in the treatment of malignant mesothelioma, by H.L. Kindler, J.P. van Meerbeeck (Seminars in Oncology, 2002).

The study

• Authors: H.L. Kindler, J.P. van Meerbeeck
• Journal: Seminars in Oncology
• Published: 2002;29(1):70-6
• Type of article: Review
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Gemcitabine is broadly active in a variety of solid tumors, including malignant mesothelioma. In vitro, gemcitabine demonstrates activity against mesothelioma cell lines. The role of single-agent gemcitabine in patients with mesothelioma is unclear, since three phase II trials treated a total of 60 patients and achieved response rates of 0%, 7%, and 31%. The combination of gemcitabine and cisplatin is synergistic against mesothelioma cell lines in vitro. Gemcitabine in combination with cisplatin or carboplatin shows definite activity in phase II trials. The trial by Byrne and colleagues that demonstrated a response rate of 48% established the combination of gemcitabine plus cisplatin as a standard therapy for this disease in the United States. Subsequent multicenter trials have achieved lower response rates of 26% and 16% for this combination. Gemcitabine plus carboplatin also has activity. Future roles for gemcitabine in malignant mesothelioma patients include incorporating a gemcitabine/platinum regimen for neoadjuvant or adjuvant therapy, combining it with other cytotoxic chemotherapy agents such as pemetrexed or vinorelbine, or adding novel cytostatic agents such as the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, to the gemcitabine and platinating agent combination.

Copyright 2002 by W.B. Saunders Company.

In plain English

This article is a review, not a new study. The authors summarized published and preliminary phase II trials of the chemotherapy drug gemcitabine in malignant mesothelioma. Three trials tested gemcitabine alone. Response rates were 7% (95% CI, 1% to 24%) among 27 patients with pleural mesothelioma in a European (EORTC) trial, 0% among 17 patients in a US (CALGB) trial, and 31% among 16 evaluable patients in a German trial reported only in abstract. The authors attributed these differences to patient selection, methods and sample size. Other trials combined gemcitabine with cisplatin. Response rates were 47.6% (95% CI, 26.2% to 69%) among 21 patients in a single-center Australian trial, 26% (95% CI, 14% to 38%) among 46 assessable patients in a multicenter Australian trial, and 16% among 25 evaluable patients in a European trial. Gemcitabine with carboplatin produced partial responses in 20% of 20 patients (95% CI, 6% to 43%). The authors concluded that gemcitabine plus a platinum drug has definite antitumor activity and is a reasonable first-choice regimen. They noted that phase III survival data are lacking. The article does not discuss asbestos exposure.

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: Review of phase II clinical trials of gemcitabine, alone or with a platinum drug, in malignant mesothelioma. Some of the reviewed trials were published only as abstracts or preliminary results.
• Who was studied: Patients with malignant mesothelioma in the reviewed trials. Single-agent trials: 27 eligible patients with pleural mesothelioma (EORTC), 17 patients (CALGB), and 16 evaluable of 23 patients (German trial). Combination trials: 21 patients (Byrne, Australia), 46 assessable of 53 patients (multicenter Australian trial), 25 evaluable of 32 patients (European trial), and 20 patients (gemcitabine plus carboplatin).
• Exposure: Not asbestos. The treatment studied was gemcitabine chemotherapy, given alone at 1,250 to 1,500 mg/m2 or combined with cisplatin or carboplatin. The article gives no information on asbestos exposure.
• Main results:
  • EORTC single-agent trial (27 eligible patients with pleural mesothelioma): two partial responses, a response rate of 7% (95% CI, 1% to 24%). Median survival after the start of treatment was 8 months.
  • CALGB single-agent trial (17 patients): no objective responses. Median survival was 4.7 months (95% CI, 3.1 to 12.9 months).
  • German single-agent trial (reported only as an abstract): 5 of 16 evaluable patients had tumor regression, an overall response rate of 31%.
  • Single-center Australian gemcitabine plus cisplatin trial (Byrne et al, 21 patients): 10 partial responses, an overall response rate of 47.6% (95% CI, 26.2% to 69%). Median survival was 41 weeks.
  • Multicenter Australian gemcitabine plus cisplatin trial: 12 of 46 assessable patients had a partial response, an overall response rate of 26% (95% CI, 14% to 38%). Median survival was 7.5 months.
  • European gemcitabine plus cisplatin trial (van Haarst et al, preliminary results): partial responses in four of the 25 evaluable patients, an overall response rate of 16%.
  • Gemcitabine plus carboplatin trial (Aversa et al, 20 patients): partial response in 20% of patients (95% CI, 6% to 43%) and no complete responses.
• The authors' conclusion: The authors concluded that the trials provide level 3 evidence that gemcitabine combined with a platinum drug has definite antitumor activity. In the absence of phase III data, they considered it a reasonable first-choice chemotherapy regimen for malignant mesothelioma. They wrote that it remains unclear whether gemcitabine alone has more than modest activity.
• Limitations the authors state:
  • There are no phase III trial data to assess whether gemcitabine-based treatment affects survival.
  • The authors attributed the differing single-agent response rates to differences in patient selection, methodology and sample size between trials.
  • The German trial was reported only in abstract form. It did not define its response criteria or report how many patients were assessed only by chest radiograph.
  • Patients in the CALGB trial were older, had worse performance status, and more often had mixed or sarcomatoid histology than patients in earlier CALGB trials. The authors wrote that this may partly explain its shorter survival.

Topics

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

Medical terms in this study, explained in our Lexicon: Gemcitabine, Mesothelioma, Cisplatin, Carboplatin, Adjuvant Therapy, Chemotherapy, Pemetrexed (Alimta), Vinorelbine.

Related studies

• Switch-maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma (NVALT19): an investigator-initiated, randomised, open-label, phase 2 trial — C.J. de Gooijer, V. van der Noort, et al. (2021)
• BAP1 Status Determines the Sensitivity of Malignant Mesothelioma Cells to Gemcitabine Treatment — A. Guazzelli, P. Meysami, et al. (2019)
• Gemcitabine as maintenance treatment of diffuse pleural mesothelioma: randomized phase II study — M.E. Sobeih, M. Helal, et al. (2026)
• A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus cisplatin in patients with advanced malignant pleural mesothelioma — O. Arrieta, D. López-Macías, et al. (2014)
• Gemcitabine reactivates epigenetically silenced genes and functions as a DNA methyltransferase inhibitor — S.G. Gray, A.M. Baird, et al. (2012)
• Gemcitabine-induced erysipeloid skin lesions in a patient with malignant mesothelioma — I. Kuku, E. Kaya, et al. (2002)

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