Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study

Int J Radiat Oncol Biol Phys. 2016 Jan 1;94(1):111-117. doi: 10.1016/j.ijrobp.2015.09.009. Epub 2015 Sep 18.


Purpose: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT).

Methods and materials: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years.

Results: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects*
  • Antineoplastic Agents / administration & dosage
  • Biomarkers
  • Brachytherapy / methods
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Cell Hypoxia*
  • Chemoradiotherapy / methods*
  • Cisplatin / administration & dosage
  • Drug Administration Schedule
  • Early Termination of Clinical Trials
  • Female
  • Follow-Up Studies
  • Humans
  • Niacinamide / administration & dosage
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Oxygen / metabolism
  • Partial Pressure
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / adverse effects*
  • Radiation Tolerance / drug effects
  • Sorafenib
  • Time Factors
  • Tumor Burden
  • Uterine Cervical Neoplasms / blood supply
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Biomarkers
  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib
  • Cisplatin
  • Oxygen