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

Abstract

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 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.

Sunitinib dosing schedule 2/1 improves tolerability, efficacy, and health-related quality of life in Chinese patients with metastatic renal cell carcinoma

“…Patients who are unable to tolerate severe AEs on the schedule 4/2 (either at the standard or a modified dosage) are generally switched to an alternative dosing schedule. In recent years, there has been increasing evidence that the schedule 2/1 is associated with a lower frequency of dose reductions or treatment interruptions and has a comparable or even better oncological outcome than the traditional schedule 4/2, especially in Asian patients [11][12][13]22].…”

Molecular‐targeted therapy in advanced renal cell carcinoma based on pharmacokinetics, pharmacodynamics and pharmacogenetics: A proposed strategy

“…Several studies described the clinical benefit of an alternative administration schedule, such as 2 weeks of treatment and 1 week off (2/1) instead of the standard 4 weeks of treatment and 2 weeks off (4/2) schedule . According to the pharmacological data, both schedules were shown to have almost the same amount of time with C 0 in the therapeutic range.…”

Editorial Comment from Dr Yokomizo to Efficacy of traditional and alternative sunitinib treatment schedules in Japanese patients with metastatic renal cell carcinoma

“…1 Owing to its prominent treatment efficacy, sunitinib is one of the most widely prescribed drugs for the treatment of metastatic renal cell cancer (RCC). However, almost all patients experience treatment-related adverse events, such as fatigue, bone marrow suppression, hand-foot syndrome, stomatitis, hypertension or hypothyroidism, 1 and dose modification is required for most patients to continue therapy. The traditional dosing schedule for sunitinib is 50 mg administered daily with the 4 weeks on and 2 weeks off schedule.…”

“…The traditional dosing schedule for sunitinib is 50 mg administered daily with the 4 weeks on and 2 weeks off schedule. 1 In order to decrease the toxicity and extend the duration of treatment, a recent study has reported an alternative treatment schedule for sunitinib administration involving the 2 weeks on and 1 week off schedule. 2 In this retrospective study, the altered dosing schedule not only increased patient tolerability, but also increased patient survival duration compared with the traditional schedule regimen.…”