- 1: Cancer Res. 2001 Oct 15;61(20):7501-6.
Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo.
Bello L, Carrabba G, Giussani C, Lucini V, Cerutti F, Scaglione F, Landré J, Pluderi M, Tomei G, Villani R, Carroll RS, Black PM, Bikfalvi A.
Institute of Neurosurgery, University of Milano, Ospedale Maggiore Policlinico, IRCCS, Milan, Italy.
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.
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.