Vascular disrupting agents: a delicate balance between effi... : Current Opinion in Oncology
Current Opinion in Oncology:
May 2012 - Volume 24 - Issue 3 - p 305–315
doi: 10.1097/CCO.0b013e32835249de
INNOVATIVE EARLY CLINICAL TRIALS METHODOLOGY AND NEW THERAPEUTICS IN CANCER: Edited by Ahmad Awada
Abstract
Purpose of review:
Targeting the tumor vasculature is
an attractive approach for cancer therapy. Vascular disrupting agents
(VDAs) are compounds that directly target tumor blood vessels and create
central tumor necrosis. The current review aims to summarize the
clinical development (i.e. safety and efficacy) of this class of
compounds.
Recent findings:
VDAs have demonstrated signs of
clinical activity in different tumor types [e.g. anaplastic thyroid
carcinoma (ATC), nonsmall cell lung carcinoma (NSCLC), ovarian cancer,
sarcoma]. However, the lack of predictive biomarkers to identify
patients with a high probability of response to VDAs, places this class
of compounds at a high risk of failure. This has recently been
exemplified by several negative phase II/III trials in NSCLC, ATC, and
castration-refractory metastatic prostate cancer.
Summary:
VDAs represent a unique class of anticancer
compounds. Their clinical development is hampered by cardiovascular,
neurological toxicities as single agent and by hematological toxicity in
combination with chemotherapy. Molecular predictors of their efficacy
are crucial for further development. As single agent, only few objective
responses have been observed in a variety of solid tumors. However,
VDAs have failed to demonstrate a survival advantage in several phase
II/III trials especially in combination with chemotherapy.
