Superior Tolerability of Altered Dosing Schedule of Sunitinib with 2-Weeks-on and 1-Week-off in Patients with Metastatic Renal Cell Carcinoma--Comparison to Standard Dosing Schedule of 4-Weeks-on and 2-Weeks-off

• Published in: Japanese journal of clinical oncology Vol. 44; no. 3; pp. 270 - 277
• Main Authors: Kondo, T., Takagi, T., Kobayashi, H., Iizuka, J., Nozaki, T., Hashimoto, Y., Ikezawa, E., Yoshida, K., Omae, K., Tanabe, K.
• Format: Journal Article
• Language: English
• Published: England 01.03.2014
• Subjects: Adult; Aged; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Carcinoma, Renal Cell - secondary; Diarrhea - chemically induced; Disease-Free Survival; Drug Administration Schedule; Female; Hand-Foot Syndrome - etiology; Humans; Indoles - administration & dosage; Indoles - adverse effects; Kidney Neoplasms - drug therapy; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Male; Middle Aged; Neoplasm Staging; Pyrroles - administration & dosage; Pyrroles - adverse effects; Retrospective Studies; Treatment Outcome; sunitinib; adverse drug event; renal cell carcinoma; drug tolerances; drug administration schedule
• ISSN: 0368-2811; 1465-3621; 1465-3621
• DOI: 10.1093/jjco/hyt232

Poor tolerability to sunitinib with the standard dosing schedule has become an issue. We retrospectively analyzed the treatment efficacy and the profile of adverse events of 2 weeks of sunitinib treatment followed by 1-week-off (Schedule 2/1) and compared the results with the standard dosing schedule with 4 weeks of treatment followed by 2-weeks-off (Schedule 4/2). From January 2010 until December 2012, 48 patients with metastatic renal cell carcinoma who received at least two cycles of sunitinib as first-line therapy were the subjects of this study. After 2011, we switched to Schedule 2/1 for most patients. Schedule 2/1 included 26 patients and Schedule 4/2 had 22. The incidence of most adverse events was not significantly different between the two groups except for hand-foot syndrome and diarrhoea, which were observed more frequently in Schedule 4/2 and reached statistical significance. A dose interruption due to adverse events in the first three cycles was significantly lower in Schedule 2/1 patients than in those on Schedule 4/2 (27 versus 53% P = 0.04). With respect to treatment efficacy, the objective response rate tended to be higher in Schedule 4/2 than in Schedule 2/1 (50 versus 32%), and median progression-free survival was longer in patients on Schedule 2/1 than those on Schedule 4/2 (18.4 versus 9.1 months). These differences, however, did not reach statistical significance (P = 0.14, P = 0.13). Alteration in dosing schedule of sunitinib with 2-weeks-on and 1-week-off showed a lower incidence of dose interruption and a similar oncological outcome compared with the standard dosing schedule of 4-weeks-on and 2-weeks-off.