title: Phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  Sunitinib at 50 mg/day on the 4-weeks-on-2-weeks-off schedule is the current approved regimen for advanced/metastatic renal cell carcinoma (mRCC). Escudier et al reported that continuous, once-daily dosing with sunitinib 37.5 mg had a manageable safety profile and significant antitumor activity as second-line mRCC therapy. In this prospective, multicenter, phase II study, we evaluated the activity of continuous once-daily dosing with sunitinib 37.5 mg as first-line mRCC treatment.
  
  
  METHODS
  One hundred nineteen treatment-naive patients with measurable mRCC received sunitinib. The primary endpoint was objective response; secondary endpoints included progression-free survival (PFS), safety, pharmacokinetic measurements, exploration of response biomarkers, and patient reported outcomes (PRO).
  
  
  RESULTS
  Objective response rate (ORR) was 35.3%; median response duration was 10.4 months; 36% of patients had stable disease ≥12 weeks. Median PFS at 1 year was 9 months, and 1-year survival probability was 67.8%. The most common any-grade treatment-related adverse events (AEs) were diarrhea (50%) and hand-foot syndrome (43%); the most common grade 3-4 treatment-related AEs were hand-foot syndrome (13%), neutropenia (11%), and diarrhea (9%). Steady-state pharmacokinetics were reached within 3 weeks, with no disproportionate accumulation of sunitinib or its active metabolite throughout the study. No significant correlations between trough drug, active metabolite, or soluble protein levels and clinical response were observed. PRO was largely maintained, although fatigue appeared to worsen after treatment started, with improvement over time.
  
  
  CONCLUSIONS
  Continuous once-daily dosing with sunitinib 37.5 mg was active with a manageable safety profile as first-line mRCC therapy, making this a feasible alternative dosing regimen.
authors: PUCRS School of Medicine, Porto Alegre, Brazil. chbe@via-rs.net
authors: Carlos H
authors: CH
authors: Barrios
authors: David
authors: D
authors: Hernandez-Barajas
authors: Michael P
authors: MP
authors: Brown
authors: Se-Hoon
authors: SH
authors: Lee
authors: Luis
authors: L
authors: Fein
authors: Jin-Hwang
authors: JH
authors: Liu
authors: Subramanian
authors: S
authors: Hariharan
authors: Bridget A
authors: BA
authors: Martell
authors: Jinyu
authors: J
authors: Yuan
authors: Akintunde
authors: A
authors: Bello
authors: Zhixiao
authors: Z
authors: Wang
authors: Rajiv
authors: R
authors: Mundayat
authors: Sun-Young
authors: SY
authors: Rha
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib