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|Ref Type||Journal Article|
|Authors||Zhou A, Zhang W, Chang C, Chen X, Zhong D, Qin Q, Lou D, Jiang H, Wang J|
|Title||Phase I study of the safety, pharmacokinetics and antitumor activity of famitinib.|
|Journal||Cancer chemotherapy and pharmacology|
|Abstract Text||To evaluate the safety, tolerability, pharmacokinetics and antitumor activities of famitinib (famitinib L-malate), a novel oral multitargeting tyrosine kinase inhibitor that acts against vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor, stem cell factor receptor (c-kit), FMS-like tyrosine kinase-3 receptor and protooncogene tyrosine kinase receptor in patients with advanced solid cancer.Patients received once daily oral famitinib. Doses were increased from 4 to 8, 13, 20, 27, 24, 25 and eventually 30 mg. Each cycle was defined as 28 days. The pharmacokinetic profile and various biomarkers were evaluated during the first cycle. Antitumor efficacy was evaluated every 8 weeks.Fifty-four patients were evaluable for safety and efficacy. Dose-limiting toxicities were observed in 2 of 3 patients at 30 mg. The dose-limiting toxicities observed in the first cycle of famitinib treatment included hypertension, hand-foot skin reaction and diarrhea. Grade 3 hypertriglyceridemia/hypercholesterolemia and proteinuria were notable side effects in the subsequent treatment cycles. Other common side effects included bone marrow suppression, oral mucositis, fatigue, pain, elevated transaminase or bilirubin, peripheral sensory disturbance and hypothyroidism, most of which were mild to moderate in severity. Pharmacokinetic studies revealed no significant accumulation of famitinib or its major metabolite, M3. The half-lives of famitinib and M3 were approximately 28.7-33.8 and 41.3-47.7 h, respectively. Food demonstrated a minimal effect on the pharmacokinetics of famitinib. Eight partial responses were determined, including 6 cases of renal cell carcinoma, 1 case of gastrointestinal stromal tumor (GIST) and 1 case of alveolar soft part sarcoma. Fourteen patients demonstrated stable disease with various degrees of tumor shrinkage.Famitinib is generally well tolerated. Famitinib demonstrates a wide spectrum of antitumor activities, which warrants further study in renal cell carcinoma, GIST, hepatocellular carcinoma and soft tissue sarcoma. The recommended dose for future phase II clinical trials is 25 mg.|
|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||Advanced Solid Tumor||not applicable||Famitinib||Phase I||Actionable||In a Phase I trial, patients with advanced solid tumors had antitumor activity in response to the receptor tyrosine kinase inhibitor, famitinib (PMID: 24043137).||24043137|