title: Improved health-related quality of life of patients with metastatic renal cell carcinoma treated with a 2 weeks on and 1 week off schedule of sunitinib.
abstract: The objective of this study was to investigate the significance of changes from the standard dosing schedule of sunitinib, which is 4 weeks of treatment and 2 weeks off (schedule 4/2), to an alternative schedule with 2 weeks of treatment and 1 week off (schedule 2/1), after encountering dose-limiting toxicity in 45 consecutive Japanese patients with metastatic renal cell carcinoma (mRCC). Despite a definitively improved relative dose intensity of sunitinib by changing from schedule 4/2 to 2/1, this difference was not significant. Adverse events (AEs) occurred in all patients on both schedules 4/2 and 2/1; however, the proportion of patients experiencing AEs ≥ grade 3 on schedule 2/1 was significantly lower than that on schedule 4/2. Quality of life (QOL) analysis using SF-36 revealed that all eight scores during schedule 2/1 were more favorable than those during schedule 4/2, and there were significant differences in 2 of the 8 scores between these two schedules. Furthermore, multivariate analyses, which were performed to evaluate the contribution of several AEs on schedule 2/1 to the improvement of each score in SF-36, revealed that fatigue had independent impacts on two scores, despite the lack of an independent association between any scores and the remaining AEs examined. These findings suggest that schedule 2/1 is the optimal dosing schedule of sunitinib against mRCC that balances efficacy and toxicity, since treatment on schedule 2/1 resulted in a markedly improved QOL compared with that on schedule 4/2 by relieving the profile of sunitinib-related AEs.
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan, hideakimiyake@hotmail.com.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Harada
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects*; D011788:Quality of Life; D012189:Retrospective Studies; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib