RandomizEd phase 2 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

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).

In this multicenter, randomized, open-label, phase 2 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 (MSKCC) risk group and the presence or absence of measurable lesions. The primary endpoint was the 6 month failure-free survival (FFS) rate, determined by intention-to-treat analysis.

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% vs. 37%; grade 3-4, 28% vs. 11%) and fatigue (all grades, 83% vs. 58%) were more frequently observed with schedule 4/2. There was a strong tendency towards 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.

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).

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2015 Sep 07 [Epub ahead of print]

J L Lee, M K Kim, I Park, J-H Ahn, D H Lee, H M Ryoo, C Song, B Hong, J H Hong, H Ahn

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. , Department of Hematology and Oncology, Yeungnam University College of Medicine, Daegu, Korea. , Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Internal Medicine, Gachon University Gil Medical Center, Inchon, Korea. , Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. , Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. , Department of Hematology and Oncology, Daegu Catholic University Medical Center, Daegu, Korea. , Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. , Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. , Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. , Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

PubMed

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