Study of Recombinant Human Endostatin Combined With Temozolomide and Irinotecan in Recurrent Gliomas
Status:
Recruiting
Trial end date:
2023-11-30
Target enrollment:
Participant gender:
Summary
Almost all gliomas relapse. After temozolomide rechallenge or combination with irinotecan,
the progression-free survival rate at 6 months (PFS-6%) of recurrent glioblastoma was about
21%. After treatment with irinotecan-based chemotherapy regimen, the PFS-6% of recurrent
lower-grade gliomas was 40%. The optimal chemotherapeutics of recurrent gliomas has yet to be
determined.
Anti-angiogenesis is a promising therapeutic strategy. Vascular endothelial growth factor-A
(VEGF) is the primary driver of angiogenesis in tumors. Bevacizumab, a humanized monoclonal
antibody directed against VEGF, is the prototypical anti-angiogenic drug and received
accelerated approval of the United States Food and Drug Administration (FDA) for the
treatment of recurrent glioblastoma. Bevacizumab inproved the PFS-6% (36%), but had no effect
on the overall survival (OS) (9.2 months). Moreover, the effects of bevacizumab are transient
and most patients' tumors progress just after a median time of 3-5 months. Recombinant human
endostatin (rh-ES) is an endogenous broad-spectrum angiogenesis inhibitor that has been shown
to significantly improve therapeutic efficacy when combining with conventional chemotherapy
agents in non-small-cell lung cancer, breast cancer and melanoma.
In our previous study, we retrospectively analyzed the effect and toxicity of rh-ES when
combined with temozolomide and irinotecan on adult recurrent disseminated glioblastoma. After
combined treatment, PFS-6% was 23.3%; the median PFS and OS were 3.2 and 6.9 months,
respectively, which were promising compared with that in other studies. Once patients get
radiographic remission in a short time (4 months), they may get a long PFS.The combined
regimen did not reduce the sensitivity of tumor to bevacizumab. After tumor progression from
the combined chemotherapy, bevacizumab usage could help to prolong the survival time (5.1
months versus 2.4 months). Moreover, the toxicities of the combination therapy in this study
were manageable.
On the basis of prior clinical experience, we carry out this prospective trial to confirm the
efficacy and safety of the combination of rh-ES, temozolomide and irinotecan in patients with
recurrent gliomas.