Combination therapy: intermittent sorafenib with bevacizumab yields activity and decreased toxicity.
Br J Cancer
; 102(3): 495-9, 2010 Feb 02.
Article
in En
| MEDLINE
| ID: mdl-20051952
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Antineoplastic Combined Chemotherapy Protocols
/
Neoplasms, Glandular and Epithelial
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Br J Cancer
Year:
2010
Document type:
Article
Affiliation country:
United States