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

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

Author information

1
Medical Ovarian Cancer Team, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

Abstract

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.

PMID:
20051952
PMCID:
PMC2822947
DOI:
10.1038/sj.bjc.6605514
[Indexed for MEDLINE]
Free PMC Article

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