Journal of Clinical Oncology, Vol 14, 1007-1017, Copyright © 1996 by American Society of Clinical Oncology
Chemotherapy in malignant pleural mesothelioma. A review
ST Ong and NJ Vogelzang
Department of Medicine, University of Chicago, IL, USA.
PURPOSE AND DESIGN: We reviewed the published literature of clinical
studies in malignant pleural mesothelioma, including phase II trials of the
newer antifolates and plant derivatives, as well as older single- agent and
combination chemotherapy trials. We excluded trials with less than 15
patients, although we have mentioned smaller trials in the text to make a
specific point, as well as ones that show promise. We have also included
confidence intervals when cited in the original reports, or calculated them
when absent. RESULTS: No drugs have consistently induced a response greater
than 20%. Higher response rates have been reported with detorubicin,
high-dose methotrexate, and edatrexate at 26%, 37%, and 25%, respectively,
but these have yet to be confirmed. Agents that produce response rates in
10% to 20% of patients include doxorubicin, epirubicin, mitomycin,
cyclophosphamide, ifosfamide, cisplatin, and carboplatin. Combination
chemotherapy trials do not demonstrate a consistently greater response rate
than single-agent trials. However, the combination of doxorubicin,
cisplatin, bleomycin, and mitomycin demonstrated a response rate of 44%
(95% confidence interval, 27% to 63%), but this remains unconfirmed.
Intrapleural therapy using interferon gamma, particularly for small-volume
disease, shows promise. CONCLUSION: The successful treatment of
unresectable pleural mesothelioma awaits the discovery of active drugs.
Recent trials of high-dose methotrexate and other antifolates are
encouraging. Newer agents, including suramin, should be evaluated in phase
II trials. Off-protocol combination therapy cannot be recommended over
single-agent therapy, but studies that use combinations of the newer agents
should be conducted.
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