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International Journal of Urology (2014) 21, 1065–1068

doi: 10.1111/iju.12504

Short Communication

Efficacy of traditional and alternative sunitinib treatment schedules in Japanese patients with metastatic renal cell carcinoma Takayuki Ohzeki,1 Satoshi Fukasawa,1 Atsushi Komaru,1 Takeshi Namekawa,1 Yosuke Sato,1 Kimiaki Takagi,1 Masayuki Kobayashi,1 Hirotsugu Uemura,2 Tomohiko Ichikawa3 and Takeshi Ueda1 1 Prostate Center and Division of Urology, Chiba Cancer Center, Chiba, 2Department of Urology, Graduate School of Medicine, Kinki University, Osaka, and 3Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan

Abbreviations & Acronyms AE = adverse events ALP = alkaline phosphatase AS = alternative schedule AST = aspartate aminotransferase ECOG PS = Eastern Cooperative Oncology Group performance status IFN-α = interferon alpha LDH = serum lactate dehydrogenase LLN = lower limit of normal mRCC = metastatic renal cell carcinoma MSKCC = Memorial Sloan-Kettering Cancer Center OS = overall survival PFS = progression-free survival TS = traditional schedule TTF = time to treatment failure ULN = upper limit of normal WBC = white blood cell Correspondence: Takeshi Ueda M.D., Ph.D., Prostate Center and Division of Urology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717, Japan. Email: [email protected] Received 25 October 2013; accepted 20 April 2014. Online publication 15 June 2014

© 2014 The Japanese Urological Association

Abstract: We report the adverse events and efficacy of traditional (4 weeks on 2 weeks off) and alternative sunitinib treatment schedules for Japanese patients with metastatic renal cell carcinoma. We retrospectively investigated 54 patients who received sunitinib for metastatic renal cell carcinoma between May 2006 and June 2012: 32 received a traditional treatment schedule and 22 received an alternative schedule. According to the Memorial Sloan-Kettering Cancer Center risk classification, five patients had favorable prognoses, 42 had intermediate prognoses and seven had poor prognoses. The mean observation periods were 16.3 and 20 months for the traditional and alternative schedule groups, respectively. Adverse events were significantly less common in the alternative schedule group, including most high-grade events. In the traditional and alternative schedule groups, median times to failure were 4.1 and 11.6 months (P = 0.040), median progression-free survival times were 4.1 and 11.3 months (P = 0.031), and median overall survival times were 12.0 and 32.1 months (P = 0.018), respectively. Each of these measures was better in the group of patients who received an alternative treatment schedule, suggesting that individualized changes to the sunitinib administration schedule can be effective. Key words: alternative schedule, renal cell carcinoma, sunitinib.

Introduction Sunitinib malate (SUTENT; Pfizer, New York, NY, USA) is an orally administered, multitargeted inhibitor of vascular endothelial growth factor receptors, platelet-derived growth factor receptors and other receptor tyrosine kinases.1 Sunitinib is approved as first- and second-line treatment for advanced mRCC worldwide, including in Japan. In a randomized phase III trial, sunitinib at 50 mg/day with a 4 weeks on 2 weeks off schedule (4/2 schedule) showed superior efficacy to IFN-α as first-line therapy for mRCC. Median PFS times were 11 and 5 months (P < 0.001) in the sunitinib and IFN-α arms, respectively, and median OS exceeded 2 years in both arms.2 Sunitinib at 50 mg/day with the 4/2 schedule is the approved standard dosing for mRCC. In many cases, however, doses must be reduced or therapy must be discontinued as a result of toxicities, including hand–foot syndrome and malaise.3 Recently, switching from traditional to alternative schedules of sunitinib treatment was reported to be effective.4,5 However, no studies on this topic have been carried out in Japan. Japanese patients with mRCC experience substantially different AE than do patients in many other nations, presumably because of underlying genetic differences. Accordingly, we retrospectively examined the AE and efficacy of sunitinib administered to Japanese patients with mRCC using traditional and alternative schedules.

Methods Patients We retrospectively analyzed the medical records of 54 patients with mRCC who received treatment with sunitinib between May 2006 and June 2012 at the Prostate Center and Division of Urology, Chiba Cancer Center. The patients had received sunitinib as first-line therapy, as well as interferon therapy or other molecular target treatments as second-line therapies. At the time of sunitinib administration, patients were evaluated according to the MSKCC risk classification.6 For patients who underwent second-line therapy, the relevant risk factors were ECOG PS, low hemoglobin levels and high calcium levels. For patients who underwent first-line therapy, additional risk factors were elevated lactate dehydrogenase, and an interval of

Efficacy of traditional and alternative sunitinib treatment schedules in Japanese patients with metastatic renal cell carcinoma.

We report the adverse events and efficacy of traditional (4 weeks on 2 weeks off) and alternative sunitinib treatment schedules for Japanese patients ...
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