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Safety and Pharmacokinetics of Sorafenib Combined With Capecitabine in Patients With Advanced Solid Tumors: Results of a Phase 1 Trial.
- Source :
-
Journal of Clinical Pharmacology . Dec2011, Vol. 51 Issue 12, p1674-1684. 11p. - Publication Year :
- 2011
-
Abstract
- Sorafenib (twice daily [bid]) plus capecitabine (2 weeks on schedule/1 week off schedule) safety and pharmacokinetics were investigated in patients with advanced solid tumors (N = 35). Cohort 1 (n = 13) included sorafenib 200 mg bid and capecitabine 1050 mg/m2 bid; cohort 2 (n = 4), sorafenib 400 mg bid and capecitabine 1050 mg/m2 bid; cohort 3 (n = 6), sorafenib 200 mg bid and capecitabine 1050 mg/m2 bid (cycles 1 and 2), then 400 mg bid and capecitabine 1050 mg/m2 bid (cycle 3 onwards); and cohort 4 (n = 12), sorafenib 400 mg bid and capecitabine 850 mg/m2 bid. The combination of sorafenib and capecitabine was generally well tolerated. Most frequent drug-related adverse events were hand-foot skin reaction (HFSR, 89%), diarrhea (71%), and fatigue (69%). The HFSR was dose-limiting toxicities in 6 patients. Sorafenib exposure (Cmax and AUC0–12) was unaffected by concomitant capecitabine. Concomitant sorafenib moderately increased capecitabine and 5-fluorouracil (metabolite) exposure when the capecitabine dose was 1050 mg/m2 bid. Simultaneous administration of 400 mg bid sorafenib and 850 mg/m2 bid capecitabine, however, had only minor effects on the exposure to capecitabine and 5-fluorouracil. Based on the overall toxicity profile and pharmacokinetic parameters, the recommended phase 2 doses were therefore sorafenib 400 mg bid and capecitabine 850 mg/m2 bid, as scheduled above. [ABSTRACT FROM PUBLISHER]
Details
- Language :
- English
- ISSN :
- 00912700
- Volume :
- 51
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 67672613
- Full Text :
- https://doi.org/10.1177/0091270010386226