PMID- 19730791
OWN - NLM
STAT- MEDLINE
DCOM- 20110203
LR  - 20221207
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 28
IP  - 6
DP  - 2010 Dec
TI  - Phase I/II study of sunitinib malate in Japanese patients with gastrointestinal 
      stromal tumor after failure of prior treatment with imatinib mesylate.
PG  - 866-75
LID - 10.1007/s10637-009-9306-9 [doi]
AB  - PURPOSE: To establish a recommended sunitinib dosing schedule in Japanese 
      patients with imatinib-resistant/intolerant gastrointestinal stromal tumor (GIST) 
      and to evaluate the efficacy, safety/tolerability, pharmacokinetics, and 
      pharmacodynamics of sunitinib using this schedule. PATIENTS AND METHODS: In the 
      phase I part of this open-label phase I/II trial, Japanese GIST patients received 
      25, 50, or 75 mg/day of sunitinib on Schedule 4/2 (4 weeks on treatment; 2 weeks 
      off treatment) following imatinib failure. In phase II, patients received the 
      recommended (maximum tolerated) dose on this schedule; the primary endpoint was 
      clinical benefit rate (CBR; percent objective responses or stable disease [SD] 
      >/=22 weeks). Additional efficacy, safety, pharmacokinetic, and biomarker analyses 
      were performed. RESULTS: In phase I (12 patients), the recommended dose was 
      determined to be 50 mg/day. Sunitinib pharmacokinetics were similar to those 
      observed in studies with Western patients. In the phase II part (36 patients), 
      the CBR was 39% (95% CI: 23-57%; 11% partial responses, 28% SD >/=22 weeks). The 
      most common treatment-related non-hematologic adverse events (AEs) were hand-foot 
      syndrome (86%) and fatigue (67%). A trend towards a correlation between decreases 
      from baseline in plasma soluble KIT levels and improved CB was found. 
      CONCLUSIONS: The pharmacokinetics observed and clinical outcomes achieved in 
      Japanese GIST patients on sunitinib (50 mg/day, Schedule 4/2) after imatinib 
      failure appeared similar to those of Western patients in previous sunitinib 
      trials. Although some serious AEs were observed, AEs were generally manageable 
      using dose interruption/modification and/or standard medical treatments.
FAU - Shirao, Kuniaki
AU  - Shirao K
AD  - Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan. 
      kshirao@med.oita-u.ac.jp
FAU - Nishida, Toshirou
AU  - Nishida T
FAU - Doi, Toshihiko
AU  - Doi T
FAU - Komatsu, Yoshito
AU  - Komatsu Y
FAU - Muro, Kei
AU  - Muro K
FAU - Li, Yinhua
AU  - Li Y
FAU - Ueda, Eiji
AU  - Ueda E
FAU - Ohtsu, Atsushi
AU  - Ohtsu A
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Indoles)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/adverse effects/blood/pharmacokinetics/therapeutic use
MH  - *Asian People
MH  - Benzamides
MH  - Biomarkers, Tumor/blood
MH  - Demography
MH  - Female
MH  - Gastrointestinal Stromal Tumors/blood/*drug therapy
MH  - Humans
MH  - Imatinib Mesylate
MH  - Indoles/adverse effects/blood/pharmacokinetics/*therapeutic use
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/blood
MH  - Piperazines/*therapeutic use
MH  - Pyrimidines/*therapeutic use
MH  - Pyrroles/adverse effects/blood/pharmacokinetics/*therapeutic use
MH  - Solubility
MH  - Sunitinib
MH  - Treatment Failure
MH  - Young Adult
EDAT- 2009/09/05 06:00
MHDA- 2011/02/04 06:00
CRDT- 2009/09/05 06:00
PHST- 2009/07/08 00:00 [received]
PHST- 2009/08/11 00:00 [accepted]
PHST- 2009/09/05 06:00 [entrez]
PHST- 2009/09/05 06:00 [pubmed]
PHST- 2011/02/04 06:00 [medline]
AID - 10.1007/s10637-009-9306-9 [doi]
PST - ppublish
SO  - Invest New Drugs. 2010 Dec;28(6):866-75. doi: 10.1007/s10637-009-9306-9.