Evaluation of continuous-infusion alpha-difluoromethylornithine therapy for colorectal carcinoma.
A total of 32 evaluable patients with measurable advanced colorectal carcinoma were treated with continuous-infusion alpha-difluoromethylornithine (DFMO) at a median daily dose of 8 g/m2 (range, 6-14 g/m2). DFMO was infused over 24 h daily for 28 days, followed by a rest period of 7 days. Of the 32 patients, 14 had received no prior chemotherapy. A total of 65 courses was given, with the median being 2 (range, 1-9 courses). None of the patients achieved a partial or complete response; however, 3 patients achieved a minor response and 14 had stable disease. The frequent toxic effects of DFMO included thrombocytopenia (which was dose-limiting), malaise, nausea, vomiting, reversible hearing loss, and diarrhea. Our data suggest that continuous-infusion DFMO therapy is feasible and results in only mild gastrointestinal toxicity. Although DFMO proved to be ineffective as a single agent in this trial, it could probably best be used in combination with cytotoxic agents known to enhance its antitumor activity in a preclinical setting.
Ajani
J A
JA
Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Ota
D M
DM
Grossie
V B
VB
Abbruzzese
J L
JL
Faintuch
J S
JS
Patt
Y Z
YZ
Jackson
D E
DE
Levin
B
B
Nishioka
K
K
D002277:Carcinoma / Q000097:blood / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy*; D004341:Drug Evaluation; D004361:Drug Tolerance; D000518:Eflornithine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D065108:Ornithine Decarboxylase Inhibitors; D012074:Remission Induction; D013997:Time Factors
D065108:Ornithine Decarboxylase Inhibitors; D000518:Eflornithine