A phase II study of troglitazone, an activator of the PPARgamma receptor, in patients with chemotherapy-resistant metastatic colorectal cancer.
OBJECTIVE
Troglitazone, a potent activator of the peroxisome proliferator-activated receptor-gamma, induces tumor differentiation in human liposarcomas and causes regression of tumors that are derived from human colon cancer cells in nude mice. We therefore assessed the efficacy of troglitazone in the treatment of metastatic colon cancer in humans.


METHODS
Twenty-five patients with metastatic colorectal cancer were treated with oral troglitazone. Patients were followed up for evidence of toxicity, tumor response, and survival.


RESULTS
The treatment was well tolerated: no grade 3/4 treatment-related toxicities were observed. However, no objective tumor responses were noted, and all 25 patients had progressive disease as their best response to therapy. The median progression-free survival time was only 1.6 months, and the median survival time was 3.9 months.


CONCLUSIONS
Troglitazone is not an active agent for the treatment of metastatic colorectal cancer.
Kulke
Matthew H
MH
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Demetri
George D
GD
Sharpless
Norman E
NE
Ryan
David P
DP
Shivdasani
Ramesh
R
Clark
Jeffrey S
JS
Spiegelman
Bruce M
BM
Kim
Haesook
H
Mayer
Robert J
RJ
Fuchs
Charles S
CS
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002839:Chromans / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D016019:Survival Analysis; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists*; D017211:Treatment Failure; D016896:Treatment Outcome; D000077288:Troglitazone
D000970:Antineoplastic Agents; D002839:Chromans; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone