Received: 29 September 2016 Accepted: 27 February 2017 Published on: 21 April 2017
Real-world experience of the feasibility and tolerability
of the 2/1 dosing schedule with sunitinib in the treatment of
patients with advanced renal cell carcinoma in Australia
Royal North Shore Hospital, NSW, Australia
Crown Princess Mary Cancer Centre, West-
mead Hospital, NSW, Australia
Western Health, VIC, Australia
Northern Cancer Institute, NSW, Australia
Megan Crumbaker, Crown Princess Mary Cancer
Centre, Westmead Hospital, Clinical Trials Unit,
Westmead NSW 2145, Australia.
Presented in part at the Australian and New
Zealand Urogenital and Prostate (ANZUP)
Cancer Trials Group Annual Scientific Meeting
held on 10–12 July 2016 in Brisbane, QLD, as a
Aim: Sunitinib is a first-line treatment option for metastatic renal cell carcinoma (mRCC) funded
by the Australian Pharmaceutical Benefits Scheme. Toxicities are common with the standard
schedule leading to alternative dosing schedules to be suggested. We reviewed Australian treat-
ment practices to evaluate the safety and outcomes of patients on a 2 weeks on, 1 week off treat-
ment schedule (2/1).
Methods: We performed a retrospective review of 63 patients with mRCC treated with first-line
sunitinib on a 2/1 schedule at four Australian centers.
Results: Forty-six patients (73%) initiated sunitinib on the 2/1 schedule whereas 17 (27%)
switched from the 4/2 schedule due to toxicity. Three progressing on a 4/2 schedule tolerated up-
titration of their dose with a clinical and radiological response on the 2/1 schedule. The median
duration of treatment was 31.9 months; median duration of treatment on the 2/1 schedule in
patients changing from 4/2 was 11.5 months. Few (6.3%) ceased due to toxicity. Median overall
survival was 37.2 months.
Conclusion: In this retrospective review of the 2/1 sunitinib schedule, time on treatment with clin-
ical benefit exceeded the overall survival times seen in the phase III trials utilizing the 4/2 schedule.
Overall survival also exceeded that seen in these trials. Few patients ceased due to toxicity. The
2/1 schedule appears to be an acceptable schedule to use in selected patients with mRCC both at
initiation of first-line treatment and in those intolerant to the 4/2 schedule.
renal cell carcinoma, schedule, sunitinib, toxicity
The orally administered multitargeted tyrosine kinase inhibitor suni-
tinib is a standard first-line treatment for metastatic renal cell
carcinoma (mRCC). The dose and schedule approved by the Aus-
tralian Therapeutic Goods Administration (TGA) and funded by the
Pharmaceutical Benefits Scheme is a 6-week dosing cycle com-
prising sunitinib 50 mg/day for 4 weeks, followed by a 2-week
rest period (Schedule 4/2), and repeated until disease progression.
However, phase III and ‘real-world’ data indicate that this sched-
ule can result in adverse events necessitating dose reductions or
delays in up to 50% of patients and discontinuation of therapy in
a further 10–20% of patients.
Maintaining dose intensity and
target plasma concentrations of sunitinib is essential for optimal clin-
ical outcomes in patients with mRCC.
The challenge, therefore, is
to minimize toxicity while maintaining sunitinib systemic exposure
intensity and maximizing treatment adherence and overall time on
Alternative sunitinib dosing regimens have been studied in patients
with mRCC with the goal of providing a better safety profile than the
Continuous daily dosing with sunitinib 37.5 mg daily
has been investigated in two prospective single-arm phase II studies.
Overall response rate was 20% in 107 cytokine pretreated patients
and 35% in 119 treatment naïve patients.
survival was 8.2 and 9.0 months.
The spectrum of toxicity was sim-
ilar in both studies. A single randomized phase II study compared the
Asia-Pac J Clin Oncol. 2018;14:e45–e49.
2017 John Wiley & Sons Australia, Ltd e45wileyonlinelibrary.com/journal/ajco