PMID- 19282169
OWN - NLM
STAT- MEDLINE
DCOM- 20090811
LR  - 20220408
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 45
IP  - 11
DP  - 2009 Jul
TI  - Clinical evaluation of continuous daily dosing of sunitinib malate in patients 
      with advanced gastrointestinal stromal tumour after imatinib failure.
PG  - 1959-68
LID - 10.1016/j.ejca.2009.02.011 [doi]
AB  - AIMS: To assess the antitumour activity, safety, pharmacokinetics and 
      pharmacodynamics of continuous daily sunitinib dosing in patients with 
      imatinib-resistant/intolerant gastrointestinal stromal tumour (GIST) and to 
      assess morning dosing versus evening dosing. PATIENTS AND METHODS: In this 
      open-label phase II study, patients were randomised to receive morning or evening 
      dosing of sunitinib 37.5mg/day. The primary end-point was clinical benefit rate 
      (CBR; percent complete responses+partial responses [PRs]+stable disease [SD] 24 
      weeks). Secondary end-points included progression-free survival (PFS), overall 
      survival (OS), safety, pharmacokinetic parameters and plasma biomarker levels. 
      RESULTS: Sixty of 61 planned patients received treatment (30 per dosing group); 
      26 completed the study. Overall, the CBR was 53% (95% exact CI, 40-66): eight 
      patients (13%) achieved objective PRs; 24 (40%) achieved SD 24 weeks. Median PFS 
      was 34 weeks (95% CI, 24-49); median OS was 107 weeks (95% CI, 72 - not yet 
      calculable). Most adverse events (AEs) were of grade 1 or 2 in severity, and were 
      manageable through dose modification or standard interventions. No new AEs were 
      apparent compared with the approved intermittent dosing schedule. Antitumour 
      activity and safety were generally similar with morning and evening dosing. 
      Continuous daily sunitinib dosing achieved and sustained effective drug 
      concentrations without additional accumulation across cycles. Decreases from 
      baseline in plasma levels of soluble KIT after 20 and 24 weeks of dosing 
      correlated with longer OS. CONCLUSION: For patients with 
      imatinib-resistant/intolerant GIST, continuous daily sunitinib dosing appears to 
      be an active alternative dosing strategy with acceptable safety.
FAU - George, S
AU  - George S
AD  - Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute,Boston, MA 
      02115, USA. suzanne_george@dfci.harvard.edu
FAU - Blay, J Y
AU  - Blay JY
FAU - Casali, P G
AU  - Casali PG
FAU - Le Cesne, A
AU  - Le Cesne A
FAU - Stephenson, P
AU  - Stephenson P
FAU - Deprimo, S E
AU  - Deprimo SE
FAU - Harmon, C S
AU  - Harmon CS
FAU - Law, C N J
AU  - Law CN
FAU - Morgan, J A
AU  - Morgan JA
FAU - Ray-Coquard, I
AU  - Ray-Coquard I
FAU - Tassell, V
AU  - Tassell V
FAU - Cohen, D P
AU  - Cohen DP
FAU - Demetri, G D
AU  - Demetri GD
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090311
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Benzamides)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Indoles)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-3)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/blood/pharmacokinetics/*therapeutic use
MH  - Benzamides
MH  - Biomarkers, Tumor/blood
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Gastrointestinal Stromal Tumors/blood/*drug therapy/mortality
MH  - Humans
MH  - Imatinib Mesylate
MH  - Indoles/blood/pharmacokinetics/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Piperazines/therapeutic use
MH  - Proto-Oncogene Proteins c-kit/blood
MH  - Pyrimidines/therapeutic use
MH  - Pyrroles/blood/pharmacokinetics/*therapeutic use
MH  - Sunitinib
MH  - Survival Rate
MH  - Treatment Outcome
MH  - Vascular Endothelial Growth Factor A/blood
MH  - Vascular Endothelial Growth Factor Receptor-2/blood
MH  - Vascular Endothelial Growth Factor Receptor-3/blood
EDAT- 2009/03/14 09:00
MHDA- 2009/08/12 09:00
CRDT- 2009/03/14 09:00
PHST- 2009/02/04 00:00 [received]
PHST- 2009/02/05 00:00 [accepted]
PHST- 2009/03/14 09:00 [entrez]
PHST- 2009/03/14 09:00 [pubmed]
PHST- 2009/08/12 09:00 [medline]
AID - S0959-8049(09)00101-4 [pii]
AID - 10.1016/j.ejca.2009.02.011 [doi]
PST - ppublish
SO  - Eur J Cancer. 2009 Jul;45(11):1959-68. doi: 10.1016/j.ejca.2009.02.011. Epub 2009 
      Mar 11.