Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated with Radiotherapy: Results of a Phase I Clinical Study
Mené sur 13 patientes atteintes d'un cancer du col de l'utérus de stade IB à IIIB (durée médiane de suivi : 4,5 ans), cet essai de phase I montre que le sorafenib, administré avant une radiothérapie en combinaison avec une chimiothérapie concomitante par cisplatine, augmente l'hypoxie tumorale
Purpose : Pre-clinical studies have shown that angiogenesis inhibition can improve response to radiotherapy (RT). The purpose of this phase I study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). Methods and Materials : Thirteen stage IB to IIIB patients participated. Sorafenib was administered daily for seven days prior to the start of standard RTCT in patients with early stage, low-risk disease, as well as during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion and hypoxia were measured at baseline and again after seven days of sorafenib alone prior to the start of RTCT. The median follow-up was 4.5 years. Results : Initial complete response was seen in 12 patients. One died without achieving disease control and four developed recurrent disease. One patient with an extensive, infiltrative tumor developed pelvic fistulae during treatment. The 4-year actuarial survival was 85%. Late, grade 3 gastrointestinal toxicity developed in four patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. Conclusions : Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT.