Combination therapy: intermittent sorafenib with bevacizumab yields activity and decreased toxicity

Br J Cancer. 2010 Feb 2;102(3):495-9. doi: 10.1038/sj.bjc.6605514. Epub 2010 Jan 5.


Background: We previously reported preliminary results of our phase I study of continuous daily sorafenib with bevacizumab every other week for solid tumours. Toxicity was moderate, leading to additional dose levels (DL) testing intermittent sorafenib dosing.

Methods: Seventeen patients with advanced solid tumours were treated on three additional DLs testing sorafenib days 1-5 per week. Dose level 4 was sorafenib 200 mg twice daily (b.i.d.) and bevacizumab 5 mg kg(-1). DL5 alternated between bevacizumab 10 mg kg(-1)-sorafenib 200 mg b.i.d. (A) and sorafenib 400 mg b.i.d. with bevacizumab 5 mg kg(-1) (B). Outcome and toxicity data from 19 epithelial ovarian cancer (EOC) patients from DL 1-5 were analysed.

Results: Fewer patients required sorafenib dose reduction with the intermittent schedule (41 vs 74% daily, P=0.01). Hand-foot skin reaction (HFSR) remained the primary cause of dose reduction (n=5). Partial responses (12%) or disease stabilisation > or =4 months (53%; median 6 (4-26)) occurred in most patients on the intermittent schedule. Partial response occurred in 47% EOC patients treated in pooled analysis of duration 4-37 months.

Conclusion: Intermittent sorafenib dosing with bevacizumab has promising clinical activity and less sorafenib dose reduction and side effects, but does not ameliorate HFSR. We are conducting a phase II clinical trial with intermittent sorafenib and bevacizumab in patients with EOC.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzenesulfonates / administration & dosage
  • Benzenesulfonates / adverse effects
  • Bevacizumab
  • Female
  • Humans
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Niacinamide / analogs & derivatives
  • Ovarian Neoplasms / drug therapy*
  • Phenylurea Compounds
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Sorafenib


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Benzenesulfonates
  • Phenylurea Compounds
  • Pyridines
  • Niacinamide
  • Bevacizumab
  • Sorafenib