PMID- 19193781
OWN - NLM
STAT- MEDLINE
DCOM- 20090728
LR  - 20151119
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Linking)
VI  - 14
IP  - 2
DP  - 2009 Feb
TI  - Approval summary: imatinib mesylate in the treatment of metastatic and/or 
      unresectable malignant gastrointestinal stromal tumors.
PG  - 174-80
LID - 10.1634/theoncologist.2008-0255 [doi]
AB  - The purpose of the present application was to fulfill a postmarketing commitment 
      to provide long-term efficacy and safety data on treatment with imatinib mesylate 
      (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ) in patients with CD117(+) 
      unresectable and/or metastatic malignant gastrointestinal stromal tumors (GISTs). 
      In addition, this application also provides evidence to support a change in the 
      label to allow for an escalation of imatinib dosing to 800 mg/day for patients 
      with progressive disease on a lower dose. Two open-label, controlled, 
      multicenter, intergroup, international, randomized phase III studies were 
      submitted -- one conducted by the European Organization for Research and 
      Treatment of Cancer (n = 946) and the other by the Southwest Oncology Group (n = 
      746). These studies compared 400 mg/day of imatinib with 800 mg/day of imatinib. 
      A combined analysis of the two studies was prospectively defined and agreed to by 
      both groups. Both protocols allowed patients randomized to the 400-mg/day 
      imatinib arm to cross over to 800 mg/day imatinib at progression. Objective 
      responses were achieved in >50% of patients receiving either imatinib dose. The 
      median progression-free survival time was approximately 20 months and the median 
      overall survival (OS) time was approximately 49 months. In the combined analysis, 
      347 patients crossed over to 800 mg/day imatinib at the time of progression. The 
      median OS time after crossover was 14.3 months. The most common adverse events 
      (AEs) were fluid retention, nausea, fatigue, skin rash, gastrointestinal 
      complaints, and myalgia. The most common laboratory abnormality was anemia. Most 
      often the AEs were of mild-to-moderate severity. Fluid retention events and skin 
      rash were numerically reported more often in the 800-mg/day treatment cohort of 
      patients.
FAU - Cohen, Martin H
AU  - Cohen MH
AD  - Office of Oncology Drug Products, Center for Drug Evaluation and Research, US 
      Food and Drug Administration, Silver Spring, MD 20993-0002, USA. 
      martin.cohen@fda.hhs.gov
FAU - Farrell, Ann
AU  - Farrell A
FAU - Justice, Robert
AU  - Justice R
FAU - Pazdur, Richard
AU  - Pazdur R
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20090204
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Benzamides
MH  - Disease-Free Survival
MH  - Drug Approval
MH  - Female
MH  - Gastrointestinal Stromal Tumors/*drug therapy
MH  - Humans
MH  - Imatinib Mesylate
MH  - Male
MH  - Middle Aged
MH  - Piperazines/adverse effects/*therapeutic use
MH  - Pyrimidines/adverse effects/*therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2009/02/06 09:00
MHDA- 2009/07/29 09:00
CRDT- 2009/02/06 09:00
PHST- 2009/02/06 09:00 [entrez]
PHST- 2009/02/06 09:00 [pubmed]
PHST- 2009/07/29 09:00 [medline]
AID - theoncologist.2008-0255 [pii]
AID - 10.1634/theoncologist.2008-0255 [doi]
PST - ppublish
SO  - Oncologist. 2009 Feb;14(2):174-80. doi: 10.1634/theoncologist.2008-0255. Epub 
      2009 Feb 4.