TY - JOUR
T1 - Efficacy and Safety of an Attenuated-Dose Sunitinib Regimen in Metastatic Renal Cell Carcinoma
T2 - Results from a Prospective Registry in Singapore
AU - Tan, Hui Shan
AU - Li, Huihua
AU - Hong, Yu Wen
AU - Toh, Chee Keong
AU - Wong, Alvin
AU - Lopes, Gilberto
AU - Tay, Miah Hiang
AU - Chan, Alexandre
AU - Yao, Xin
AU - Tang, Tiffany
AU - Ng, Quan Sing
AU - Kanesvaran, Ravindran
AU - Chau, Noan Minh
AU - Tan, Min Han
N1 - Funding Information:
Dr Gilberto Lopes has received grants, personal fees, and nonfinancial support from AstraZeneca, Roche, Merck Serono, and MSD. Dr Miah Hiang Tay has received personal fees from Pfizer, GlaxoSmithKline, Sanofi, and Bayer. Dr Alexandre Chan is a consultant for GlaxoSmithKline and MSD, and has received personal fees and grants from these companies. Dr Quan Sing Ng has received personal fees from Bayer. Dr Ravindran Kanesvaran is an advisory board member and has received honoraria from GSK, Janssen, and Bayer; he is also on speakers bureaus for Pfizer and Sanofi. Dr Min-Han Tan has received research funding from Pfizer, and has filed for patents not materially involved in this study. The remaining authors have stated that they have no conflicts of interest.
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Background The use of sunitinib at conventional doses (50 mg/d, 6-week cycles: 4 weeks of treatment, then 2 weeks of no treatment) in Asian patients with metastatic renal cell carcinoma (mRCC) is associated with high real-world toxicities. Patients and Methods Patients with mRCC treated with sunitinib between 2005 and 2012 at 4 centers representing a near-national cohort (n = 160) in Singapore were evaluated. One hundred twenty-seven consecutive patients in 1 center were treated with a novel attenuated-dose sunitinib regimen (37.5 mg/d, 6-week cycle: 4 weeks of treatment, then 2 weeks of no treatment) with outcomes captured in a prospective registry. Efficacy and safety outcomes of these patients were compared against those who received sunitinib at conventional dosing (n = 33) at all 4 centers. Statistical modeling was adjusted for baseline prognostic criteria and therapy line where possible. Results Overall survival from treatment initiation (OSinitiation), overall survival from the first documented metastasis (OStotal), and progression-free survival (PFS) were similar for patients who received first-line sunitinib for conventional relative to attenuated dose regimens (OSinitiation: 18.3 vs. 16.5 months, respectively; P =.54; OStotal: 27.4 vs. 21.8 months, respectively; P =.45; PFS: 6.7 vs. 7.9 months, respectively; P =.64), similar to real-world outcomes in Western studies. A marked lower rate of severe toxicities, dose delays, and reductions were observed with the attenuated dose regimen, with 75/127 (59%), rather than 28/33 (85%) for the conventional dose arm who experienced Grade ≤ 3 toxicities (P =.0088); 31/127 (24%) rather than 19/33 (58%) who experienced dose delays (P =.0004); and 44/127 (35%) rather than 23/33 (70%) who experienced dose reduction (P =.0005) during their course of treatment. Conclusion An attenuated dose regimen of sunitinib yielded comparable real-world efficacy outcomes, with considerable reduction in toxicities as documented in a prospective registry.
AB - Background The use of sunitinib at conventional doses (50 mg/d, 6-week cycles: 4 weeks of treatment, then 2 weeks of no treatment) in Asian patients with metastatic renal cell carcinoma (mRCC) is associated with high real-world toxicities. Patients and Methods Patients with mRCC treated with sunitinib between 2005 and 2012 at 4 centers representing a near-national cohort (n = 160) in Singapore were evaluated. One hundred twenty-seven consecutive patients in 1 center were treated with a novel attenuated-dose sunitinib regimen (37.5 mg/d, 6-week cycle: 4 weeks of treatment, then 2 weeks of no treatment) with outcomes captured in a prospective registry. Efficacy and safety outcomes of these patients were compared against those who received sunitinib at conventional dosing (n = 33) at all 4 centers. Statistical modeling was adjusted for baseline prognostic criteria and therapy line where possible. Results Overall survival from treatment initiation (OSinitiation), overall survival from the first documented metastasis (OStotal), and progression-free survival (PFS) were similar for patients who received first-line sunitinib for conventional relative to attenuated dose regimens (OSinitiation: 18.3 vs. 16.5 months, respectively; P =.54; OStotal: 27.4 vs. 21.8 months, respectively; P =.45; PFS: 6.7 vs. 7.9 months, respectively; P =.64), similar to real-world outcomes in Western studies. A marked lower rate of severe toxicities, dose delays, and reductions were observed with the attenuated dose regimen, with 75/127 (59%), rather than 28/33 (85%) for the conventional dose arm who experienced Grade ≤ 3 toxicities (P =.0088); 31/127 (24%) rather than 19/33 (58%) who experienced dose delays (P =.0004); and 44/127 (35%) rather than 23/33 (70%) who experienced dose reduction (P =.0005) during their course of treatment. Conclusion An attenuated dose regimen of sunitinib yielded comparable real-world efficacy outcomes, with considerable reduction in toxicities as documented in a prospective registry.
KW - Dose modification
KW - Kidney cancer
KW - Pharmacokinetics
KW - Real-world outcomes
KW - Targeted therapy
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U2 - 10.1016/j.clgc.2014.11.004
DO - 10.1016/j.clgc.2014.11.004
M3 - Article
C2 - 25541325
AN - SCOPUS:84936985400
SN - 1558-7673
VL - 13
SP - e285-e295
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 4
ER -