Efficacy and Safety of an Attenuated-Dose Sunitinib Regimen in Metastatic Renal Cell Carcinoma: Results From a Prospective Registry in Singapore.

Abstract

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.

• Authors: Hui Shan Tan, Huihua Li, Yu Wen Hong, Chee-Keong Toh, Alvin Wong, Gilberto Lopes, Miah Hiang Tay, Alexandre Chan, Xin Yao, Tiffany Tang, Quan Sing Ng, Ravindran Kanesvaran, Noan Minh Chau, Min-Han Tan
• Journal: Clinical genitourinary cancer (Clin Genitourin Cancer) Vol. 13 Issue 4 Pg. e285-e295 (Aug 2015) ISSN: 1938-0682 [Electronic] United States
• PMID: 25541325 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Indoles
• Pyrroles
• Sunitinib

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Carcinoma, Renal Cell (drug therapy, pathology)
• Drug Administration Schedule
• Female
• Humans
• Indoles (administration & dosage, therapeutic use)
• Kidney Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Metastasis
• Prospective Studies
• Pyrroles (administration & dosage, therapeutic use)
• Singapore
• Sunitinib
• Survival Analysis
• Treatment Outcome
• Young Adult