PMID- 21898376
OWN - NLM
STAT- MEDLINE
DCOM- 20120430
LR  - 20181201
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 118
IP  - 5
DP  - 2012 Mar 1
TI  - Phase II trial of continuous once-daily dosing of sunitinib as first-line 
      treatment in patients with metastatic renal cell carcinoma.
PG  - 1252-9
LID - 10.1002/cncr.26440 [doi]
AB  - 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.
CI  - Copyright (c) 2011 American Cancer Society.
FAU - Barrios, Carlos H
AU  - Barrios CH
AD  - PUCRS School of Medicine, Porto Alegre, Brazil. chbe@via-rs.net
FAU - Hernandez-Barajas, David
AU  - Hernandez-Barajas D
FAU - Brown, Michael P
AU  - Brown MP
FAU - Lee, Se-Hoon
AU  - Lee SH
FAU - Fein, Luis
AU  - Fein L
FAU - Liu, Jin-Hwang
AU  - Liu JH
FAU - Hariharan, Subramanian
AU  - Hariharan S
FAU - Martell, Bridget A
AU  - Martell BA
FAU - Yuan, Jinyu
AU  - Yuan J
FAU - Bello, Akintunde
AU  - Bello A
FAU - Wang, Zhixiao
AU  - Wang Z
FAU - Mundayat, Rajiv
AU  - Mundayat R
FAU - Rha, Sun-Young
AU  - Rha SY
LA  - eng
SI  - ClinicalTrials.gov/NCT00338884
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20110906
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Indoles)
RN  - 0 (Pyrroles)
RN  - V99T50803M (Sunitinib)
SB  - IM
CIN - Cancer. 2012 Mar 1;118(5):1178-80. PMID: 21898373
MH  - Adult
MH  - Aged
MH  - Carcinoma, Renal Cell/*drug therapy/epidemiology/mortality/pathology
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Indoles/*administration & dosage/adverse effects
MH  - Kidney Neoplasms/*drug therapy/epidemiology/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoadjuvant Therapy
MH  - Neoplasm Metastasis
MH  - Pyrroles/*administration & dosage/adverse effects
MH  - Sunitinib
MH  - Survival Analysis
MH  - Young Adult
EDAT- 2011/09/08 06:00
MHDA- 2012/05/01 06:00
CRDT- 2011/09/08 06:00
PHST- 2010/12/22 00:00 [received]
PHST- 2011/03/30 00:00 [revised]
PHST- 2011/04/04 00:00 [accepted]
PHST- 2011/09/08 06:00 [entrez]
PHST- 2011/09/08 06:00 [pubmed]
PHST- 2012/05/01 06:00 [medline]
AID - 10.1002/cncr.26440 [doi]
PST - ppublish
SO  - Cancer. 2012 Mar 1;118(5):1252-9. doi: 10.1002/cncr.26440. Epub 2011 Sep 6.