Evaluation of self-reported progression and correlation of imatinib dose to survival in patients with metastatic gastrointestinal stromal tumors: an open cohort study.
OBJECTIVE
Self-reported progression was evaluated as a predictor of survival in patients with metastatic gastrointestinal stromal tumor (GIST).


METHODS
This is a follow-up of an open cohort study of Life Raft Group (LRG) members with a diagnosis of KIT-positive metastatic GIST receiving imatinib from May 2000-December 2007 reporting their subjective response to therapy by completion of an internet-based questionnaire. Subjects received >or= 1 year of imatinib and reported an initial positive response. Members reporting stable disease or progression were excluded. Self-reported progression-free survival (srPFS) was compared with overall survival (OS) and analyzed by starting and last reported dose.


RESULTS
One hundred sixty-nine subjects reported a mean starting dose of 527.8+/-177.9 mg/d at a mean age of 53.8+/-11.6 years at initial diagnosis. Of those reporting progression, 66% died versus 11% of those not reporting progression (P < 0.0001). When analyzed by last reported dose, a median srPFS benefit of 27.3 months was observed for the >400 mg/d group (P = 0.0017). Sixty-two percent of subjects who initiated therapy at >400 mg/d reported a dose reduction. When analyzed by last reported dose, a significant benefit in OS (P = 0.0229) and srPFS (P = 0.0069) was observed for subjects taking 600 over 400 mg/d.


CONCLUSIONS
srPFS strongly correlated with OS. Significant advantages were observed when last reported dose was considered, as was higher daily dose. These observations suggest that careful escalation to intermediate daily doses should be investigated further for its potential to reduce the incidence and severity of adverse events, but also as a strategy against developing secondary resistance to imatinib.
Call
Jerry
J
The Life Raft Group, 40 Galesi Dr, Wayne, NJ 07470, USA. jcall@liferaftgroup.org
Scherzer
Norman J
NJ
Josephy
P David
PD
Walentas
Christopher
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate