Abstract
This study evaluates the efficacy of the combination of an antiangiogenic drug and conventional chemotherapeutics for the treatment of experimental human gliomas. As an antiangiogenic, we used recombinant human PEX, a fragment of matrix metalloproteinase-2 that we have previously shown to have a significant antimitotic, anti-invasive, and antiangiogenic properties against human glioblastoma in vitro and in vivo. We used carboplatin and etoposide as the two chemotherapeutic drugs routinely used in our institution (Ospedale Maggiore de Milano) for the treatment of malignant gliomas. Conventional chemotherapeutic drugs were administered at high dose or at a low and semicontinuous regimen. Combined treatment of high-dose chemotherapy and PEX did not produce an improvement of survival in comparison with chemotherapy alone, but it was associated with a decrease in tumor volume, vascularity, and proliferative index and an increased apoptosis. All of these animals experienced severe side effects. The longest survival was documented in animals submitted to low and semicontinuous chemotherapy and antiangiogenic treatment. This regimen was associated with no side effects, marked decrease in tumor volume, vascularity, and proliferative index, and an increased apoptosis. Our data suggest that low-dose chemotherapy in combination with PEX can be successfully used against human malignant glioma in vivo.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 Supported by a Grant from Ministero della Sanità, Ricerca Finalizzata, by Ospedale Maggiore di Milano, by a Grant from Fondazione Monzino, by Associazione Italiana Ricerca sul Cancro, and by Associazione Amici della Clinica Neurochirurgica (to L. B. and R. V.) and from the Institut National de la Recherche Médicale, the Ministere de la Recherche, and the Ligue contre le Cancer (to A. B.).
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↵2 To whom requests for reprints should be addressed, at Institute of Neurosurgery, University of Milano, Ospedale Maggiore Policlinico, IRCCS, Via Francesco Sforza 35, 20122 Milan, Italy. Phone: 39-02-5503-5502; Fax: 39-02-5990-2239; E-mail: lbellorics.bwh.harvard.edu.
- Received April 11, 2001.
- Accepted August 2, 2001.
- ©2001 American Association for Cancer Research.
Volume 61, Issue 20
