title: Association of drug exposure with toxicity and clinical response in metastatic renal cell carcinoma patients receiving an attenuated dosing regimen of sunitinib.
abstract: An attenuated dosing (AD) regimen of 37.5 mg daily in repeated 4 week on, 2 week off cycles has been proposed to ameliorate frequent dose modifications caused by the toxicity observed with the approved dosing regimen of sunitinib for metastatic renal cell carcinoma (mRCC). This study aimed to determine the effect of drug exposure on toxicity and clinical response in patients receiving this regimen. All mRCC patients receiving AD sunitinib were invited to participate. In week 4 of each cycle, toxicity and plasma levels were assessed. Clinical responses were assessed after two cycles. A total of 36 patients were recruited. Patients who manifested ≥grade 2 mucositis (126.46 vs 84.81 ng/mL, p = 0.04) and altered taste (159.91 vs 105.22 ng/mL, p = 0.05) had higher total exposure than those who had grade 1 or no toxicity. Twenty-six patients completed two treatment cycles; four (15%) had partial responses, 15 (58%) had a stable disease and 7 (27%) had progressive disease. No difference in the exposure levels was found among the patients with different clinical outcomes. The AD regimen of sunitinib in Asian mRCC patients provided sufficient drug exposure with a lower incidence of toxicity, with higher drug exposure being observed in patients who experienced toxicity.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore.
authors.forename: Yi Ling
authors.initials: YL
authors.lastname: Teo
authors.forename: Xiu Ping
authors.initials: XP
authors.lastname: Chue
authors.forename: Noan Minh
authors.initials: NM
authors.lastname: Chau
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
authors.forename: Ravindran
authors.initials: R
authors.lastname: Kanesvaran
authors.forename: Hwee Lin
authors.initials: HL
authors.lastname: Wee
authors.forename: Han Kiat
authors.initials: HK
authors.lastname: Ho
authors.forename: Alexandre
authors.initials: A
authors.lastname: Chan
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D012846:Singapore; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C544393:SU 12662; D000077210:Sunitinib