title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  An attenuated dose regimen of sunitinib yielded comparable real-world efficacy outcomes, with considerable reduction in toxicities as documented in a prospective registry.
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Hui Shan
authors.initials: HS
authors.lastname: Tan
authors.affiliation: Department of Health Services Research, Singapore General Hospital, Singapore.
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.affiliation: Oncology Pharmacy, National Cancer Centre Singapore, Singapore; Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Yu Wen
authors.initials: YW
authors.lastname: Hong
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Chee-Keong
authors.initials: CK
authors.lastname: Toh
authors.affiliation: Department of Haematology-Oncology, National University Health System, Singapore.
authors.forename: Alvin
authors.initials: A
authors.lastname: Wong
authors.affiliation: Johns Hopkins International Medical Centre, Singapore.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Lopes
authors.affiliation: Onco-Care Cancer Centre, Gleneagles Hospital, Singapore.
authors.forename: Miah Hiang
authors.initials: MH
authors.lastname: Tay
authors.affiliation: Oncology Pharmacy, National Cancer Centre Singapore, Singapore; Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Chan
authors.affiliation: Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tang
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Quan Sing
authors.initials: QS
authors.lastname: Ng
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Ravindran
authors.initials: R
authors.lastname: Kanesvaran
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Noan Minh
authors.initials: NM
authors.lastname: Chau
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore; Institute of Bioengineering and Nanotechnology, Singapore. Electronic address: tan.min.han@nccs.com.sg.
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage* / Q000627:therapeutic use; D012846:Singapore; D000077210:Sunitinib; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Dose modification; Kidney cancer; Pharmacokinetics; Real-world outcomes; Targeted therapy