PMID- 19652072
OWN - NLM
STAT- MEDLINE
DCOM- 20090915
LR  - 20181201
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 27
IP  - 25
DP  - 2009 Sep 1
TI  - Phase II study of sunitinib administered in a continuous once-daily dosing 
      regimen in patients with cytokine-refractory metastatic renal cell carcinoma.
PG  - 4068-75
LID - 10.1200/JCO.2008.20.5476 [doi]
AB  - PURPOSE: Sunitinib has demonstrated antitumor activity in metastatic renal cell 
      carcinoma (mRCC) when given at 50 mg/d on a 4-weeks-on 2-weeks-off regimen. 
      Herein, we report results of an open-label, multicenter phase II mRCC study of 
      sunitinib administered on a continuous once-daily dosing regimen. PATIENTS AND 
      METHODS: Eligibility criteria included histologically proven mRCC with measurable 
      disease, failure of one prior cytokine regimen, and good performance status. 
      Patients were randomly assigned to a sunitinib starting dose of 37.5 mg/d in the 
      morning (AM) or evening (PM). RECIST-defined objective response rate (ORR) was 
      the primary end point. Secondary end points included progression-free survival 
      (PFS), overall survival (OS), adverse events (AEs), and quality-of-life measures. 
      RESULTS: One hundred seven patients were randomly assigned to AM (n = 54) or PM 
      (n = 53) dosing and on study for a median 8.3 months. Eighty-three patients 
      discontinued, 65 due to disease progression and 16 because of AEs; two patients 
      withdrew consent. Dosing was reduced to 25 mg/d in 46 patients (43%) due to grade 
      3/4 AEs. The most common grade 3 treatment-related AEs were asthenia/fatigue 
      (16%), diarrhea (11%), hypertension (11%), hand-foot syndrome (9%), and anorexia 
      (8%). ORR was 20% with a 7.2-month median response duration. Median PFS and OS 
      were 8.2 and 19.8 months, respectively, at median follow-up of 26.4 months. 
      Efficacy, tolerability, and quality-of-life results were similar between patients 
      dosed in the AM or PM. CONCLUSION: Sunitinib 37.5 mg, administered on a 
      continuous once-daily dosing regimen, has a manageable safety profile as 
      second-line mRCC therapy, providing flexible dosing, which can be explored in 
      combination studies.
FAU - Escudier, Bernard
AU  - Escudier B
AD  - Unite Immunotherapie, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 
      Villejuif Cedex, France. bernard.escudier@igr.fr
FAU - Roigas, Jan
AU  - Roigas J
FAU - Gillessen, Silke
AU  - Gillessen S
FAU - Harmenberg, Ulrika
AU  - Harmenberg U
FAU - Srinivas, Sandhya
AU  - Srinivas S
FAU - Mulder, Sasja F
AU  - Mulder SF
FAU - Fountzilas, George
AU  - Fountzilas G
FAU - Peschel, Christian
AU  - Peschel C
FAU - Flodgren, Per
AU  - Flodgren P
FAU - Maneval, Edna Chow
AU  - Maneval EC
FAU - Chen, Isan
AU  - Chen I
FAU - Vogelzang, Nicholas J
AU  - Vogelzang NJ
LA  - eng
SI  - ClinicalTrials.gov/NCT00137423
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20090803
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cytokines)
RN  - 0 (Indoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrroles)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Carcinoma, Renal Cell/*drug therapy/mortality/secondary
MH  - Cytokines/*therapeutic use
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - *Drug Resistance, Neoplasm
MH  - Europe
MH  - Female
MH  - Humans
MH  - Indoles/*administration & dosage/adverse effects/pharmacokinetics
MH  - Kaplan-Meier Estimate
MH  - Kidney Neoplasms/*drug therapy/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Protein Kinase Inhibitors/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Pyrroles/*administration & dosage/adverse effects/pharmacokinetics
MH  - Quality of Life
MH  - Sunitinib
MH  - Time Factors
MH  - Treatment Outcome
MH  - United States
EDAT- 2009/08/05 09:00
MHDA- 2009/09/16 06:00
CRDT- 2009/08/05 09:00
PHST- 2009/08/05 09:00 [entrez]
PHST- 2009/08/05 09:00 [pubmed]
PHST- 2009/09/16 06:00 [medline]
AID - JCO.2008.20.5476 [pii]
AID - 10.1200/JCO.2008.20.5476 [doi]
PST - ppublish
SO  - J Clin Oncol. 2009 Sep 1;27(25):4068-75. doi: 10.1200/JCO.2008.20.5476. Epub 2009 
      Aug 3.