Elsevier

Seminars in Oncology

Volume 29, Issue 1, February 2002, Pages 70-76
Seminars in Oncology

The role of gemcitabine in the treatment of malignant mesothelioma*

https://doi.org/10.1053/sonc.2002.30232Get rights and content

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. Semin Oncol 29:70-76. Copyright © 2002 by W.B. Saunders Company.

Section snippets

Single-agent gemcitabine in malignant mesothelioma

Three phase II trials have evaluated the efficacy of gemcitabine as a single agent in patients with malignant mesothelioma.4, 5, 6 Gemcitabine was well tolerated at doses ranging from 1,250 to 1,500 mg/m2 in chemotherapy-naive patients. Two multicenter trials documented similarly low response rates: the European Organization for Research and Treatment of Cancer (EORTC) noted a response rate of 7% in 27 patients, while the Cancer and Leukemia Group B (CALGB) observed no responses in 17 patients.4

Gemcitabine in combination with a platinating agent in mesothelioma

The combination of gemcitabine and cisplatin is synergistic in vitro in mesothelioma cell lines3 and is active in a variety of tumor types. Four groups have investigated three different schedules of gemcitabine and cisplatin in phase II trials in mesothelioma patients; response rates have ranged from 16% to 48%.7, 8, 9 Other investigators have reported preliminary results of a phase II trial of the combination of gemcitabine and carboplatin.10 These single and multicenter trials provide level 3

Future directions for the use of gemcitabine in mesothelioma

The next generation of gemcitabine trials in malignant mesothelioma will either combine gemcitabine with other agents that have known activity in this disease, or will exploit the definite activity of the gemcitabine/platinum combination in novel contexts. Objective responses have been observed in mesothelioma patients entered on phase I trials in which gemcitabine has been combined with agents with known activity in mesothelioma, such as pemetrexed or vinorelbine.19, 20 A phase II trial of the

Conclusion

Gemcitabine has in vitro activity in mesothelioma. While it remains unclear whether gemcitabine as a single agent has any more than modest activity in this disease, the combination of gemcitabine with a platinating agent has promising activity. Phase III data to assess an impact on survival are lacking. Future approaches include combining gemcitabine with active cytotoxic or cytostatic agents, and employing active combinations as part of multimodality strategies.

References (24)

  • MJ Byrne et al.

    Cisplatin and gemcitabine for malignant mesothelioma: A phase II study

    J Clin Oncol

    (1999)
  • A Nowak et al.

    Multicentre phase II study of cisplatin (C) and gemcitabine (G) in malignant mesothelioma (MM)

    Ann Oncol

    (2000)
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    *

    Address reprint requests to Hedy Lee Kindler, MD, Assistant Professor of Medicine, University of Chicago, Section of Hematology/Oncology, 5841 S Maryland Ave, MC 2115, Chicago, IL 60637.

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