Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo

This study evaluates the efficacy of the combination of an antiangiogenic d rug and conventional chemotherapeutics for the treatment of experimental hu man gliomas. As an antiangiogenic, we used recombinant human PEX, a fragmen t of matrix metalloproteinase-2 that we have previously shown to have a sig nificant antimitotic, anti-invasive, and antiangiogenic properties against human glioblastoma in vitro and it? vivo. We used carboplatin and etoposide as the two chemotherapeutic drugs routinely used in our institution (Osped ale Maggiore de Milano) for the treatment of malignant gliomas. Conventiona l chemotherapeutic drugs were administered at high dose or at a low and sem icontinuous regimen. Combined treatment of high-dose chemotherapy and PEX d id not produce an improvement of survival in comparison with chemotherapy a lone, but it was associated with a decrease in tumor volume, vascularity, a nd proliferative index and an increased apoptosis. Ail of these animals exp erienced severe side effects. The longest survival was documented in animal s submitted to low and semicontinuous chemotherapy and antiangiogenic treat ment. This regimen was associated with no side effects, marked decrease in tumor volume, vascularity, and proliferative index, and an increased apopto sis. Our data suggest that low-dose chemotherapy in combination with PEX ca n be successfully used against human malignant glioma in vivo.