Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study

Br J Cancer. 2012 May 22;106(11):1722-7. doi: 10.1038/bjc.2012.153. Epub 2012 May 8.


Background: In a phase I dose-escalation study, regorafenib demonstrated tolerability and antitumour activity in solid tumour patients. The study was expanded to focus on patients with metastatic colorectal cancer (CRC).

Methods: Patients received oral regorafenib 60-220 mg daily (160 mg daily in the extension cohort) in cycles of 21 days on, 7 days off treatment. Assessments included toxicity, response, pharmacokinetics and pharmacodynamics.

Results: Thirty-eight patients with heavily pretreated CRC (median 4 prior lines of therapy, range 0-7) were enrolled in the dose-escalation and extension phases; 26 patients received regorafenib 160 mg daily. Median treatment duration was 53 days (range 7-280 days). The most common treatment-related toxicities included hand-foot skin reaction, fatigue, voice change and rash. Twenty-seven patients were evaluable for response: 1 achieved partial response and 19 had stable disease. Median progression-free survival was 107 days (95% CI, 66-161). At steady state, regorafenib and its active metabolites had similar systemic exposure. Pharmacodynamic assessment indicated decreased tumour perfusion in most patients.

Conclusion: Regorafenib showed tolerability and antitumour activity in patients with metastatic CRC. This expanded-cohort phase I study provided the foundation for further clinical trials of regorafenib in this patient population.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / pharmacokinetics
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Pyridines / pharmacokinetics


  • Antineoplastic Agents
  • Phenylurea Compounds
  • Pyridines
  • regorafenib