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|Ref Type||Journal Article|
|Authors||Shacham-Shmueli E, Geva R, Figer A, Bulocinic S, Nalbandyan K, Shpigel S, Atsmon J, Brendel E|
|Title||Phase I trial of sorafenib in combination with 5-fluorouracil/leucovorin in advanced solid tumors.|
|Journal||Journal of clinical pharmacology|
|Abstract Text||This dose escalation, uncontrolled phase I study evaluated the tolerability, pharmacokinetics (PK), and antitumor activity of oral sorafenib 100, 200, or 400 mg twice daily (bid, continuous regimen) in combination with 5-fluorouracil/leucovorin (5-FU/LCV, intravenous infusion or bolus) in patients with advanced, solid tumors. A total of 47 patients (median age 57 years; colon cancer, 55%; pancreatic cancer, 21%; prior systemic therapy, 96%) received treatment; 24 were included in the PK analyses, and 38 were evaluable for tumor response. Treatment-emergent adverse events were observed in 98% of patients (≥grade 3, 55%); the most frequently reported were fatigue (51%), stomatitis/pharyngitis (47%), and hand-foot skin reaction (45%). Concomitant 5-FU/LCV resulted in no clinically relevant changes in the area under the plasma concentration-time curve in the dosing interval (AUC(0-12)) and maximum plasma concentration (C(max)) of sorafenib (100-400 mg bid) at steady state. Although the start of infusion until the last quantifiable plasma concentration (AUC(0-tn)) and C(max) of 5-FU were increased by concomitant sorafenib 100 to 200 mg, no consistent effect was observed with 400 mg sorafenib. Two (5%) patients with colon cancer achieved partial response; 16 (42%) patients (the majority with colon and pancreatic cancer) had stable disease. Sorafenib plus 5-FU/LCV was generally well tolerated with encouraging antitumor activity and no clinically relevant drug-drug interactions in patients with advanced solid tumors.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||colon cancer||not applicable||Fluorouracil + Sorafenib||Phase I||Actionable||In a Phase I trial, Nexavar (sorafenib) in combination with Adrucil (fluorouracil) displayed safety and efficacy in advanced solid tumors, including colon cancer (PMID: 22232731).||22232731|
|Unknown unknown||Advanced Solid Tumor||not applicable||Fluorouracil + Sorafenib||Phase I||Actionable||In a Phase I trial, Nexavar (sorafenib) in combination with Adrucil (fluorouracil) displayed safety and efficacy in advanced solid tumors, including colon cancer (PMID: 22232731).||22232731|