RandomizEd phase II trial of Sunitinib four weeks on and two weeks off versus Two weeks on and One week off in metastatic clear-cell type REnal cell carcinoma: RESTORE trial.
BACKGROUND
The standard sunitinib schedule, 4 weeks on, followed by 2 weeks off (4/2 schedule), is associated with troublesome toxicities, and maintenance of adequate sunitinib dosing and drug levels, which are essential for achieving an optimal treatment outcome, is challenging. The objective of this study was to investigate the efficacy and safety of an alternative sunitinib dosing schedule of 2 weeks on and 1 week off (2/1 schedule) compared with the standard sunitinib schedule of 4 weeks on and 2 weeks off (4/2 schedule).


METHODS
In this multicenter, randomized, open-label, phase II trial, treatment-naïve patients with clear-cell type metastatic renal cell carcinoma (mRCC) were randomly assigned to 4/2 or 2/1 schedules after stratification by Memorial Sloan Kettering Cancer Center risk group and the presence or absence of measurable lesions. The primary end point was the 6-month failure-free survival (FFS) rate, determined by intention-to-treat analysis.


RESULTS
From November 2007 to February 2014, 76 patients were accrued, and 74 were eligible. FFS rates at 6 months were 44% with the 4/2 schedule (N = 36) and 63% with the 2/1 schedule (N = 38). Neutropenia (all grades, 61% versus 37%; grade 3-4, 28% versus 11%) and fatigue (all grades, 83% versus 58%) were more frequently observed with schedule 4/2. There was a strong tendency toward a lower incidence of stomatitis, hand-foot syndrome, and rash with schedule 2/1. Objective response rates (ORRs) were 47% in schedule 2/1 and 36% in schedule 4/2. With a median follow-up of 30.0 months, the median time to progression (TTP) was 12.1 months in schedule 2/1 and 10.1 months in schedule 4/2.


CONCLUSIONS
Sunitinib administered with a 2/1 schedule is associated with less toxicity and higher FFS at 6 months than a 4/2 schedule, without compromising the efficacy in terms of ORR and TTP (NCT00570882).
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul jaelyun@amc.seoul.kr.
J L
JL
Lee
Department of Hematology and Oncology, Yeungnam University College of Medicine, Daegu.
M K
MK
Kim
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul Department of Internal Medicine, Gachon University Gil Medical Center, Inchon.
I
I
Park
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul.
J-H
JH
Ahn
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul.
D H
DH
Lee
Department of Hematology and Oncology, Daegu Catholic University Medical Center, Daegu.
H M
HM
Ryoo
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
C
C
Song
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
B
B
Hong
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
J H
JH
Hong
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
H
H
Ahn
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage*; D000077210:Sunitinib
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
alternative dosing; failure-free survival; randomized trial; renal cell carcinoma; sunitinib