Phase II trial of 9-aminocamptothecin (NSC 603071) administered as a 120-hr continuous infusion weekly for three weeks in metastatic colorectal carcinoma.
9-Aminocamptothecin (9-AC) is a camptothecin derivative with broad antitumor activity in preclinical studies. Prior investigations suggested that prolonged maintenance of 9-AC lactone plasma concentrations above 10 nmol/l and frequent administration of the drug are important determinants of antitumor activity. Our phase II study, therefore, examined a 5-day continuous infusion of 9-AC weekly for 3 weeks in patients with advanced colorectal cancer. Eighteen patients previously untreated for metastatic disease received 480 microg/m2/day of 9-AC. No responses were observed in 17 evaluable patients. Severe toxicities included granulocytopenia, nausea, vomiting and diarrhea. The median absolute granulocyte count (AGC) nadir was 2,300/microl (range 0-9,000/microl) and occurred on day 10. Eight patients received an escalated dose of 600 microg/m2/day. The median AGC nadir at the escalated dose was 1,500/microl (range: 300-2,700/microl) and occurred on day 22. The median number of courses given was 2 (range: 1-8); and the median time to disease progression was 8 weeks (range: 1-40 weeks). 9-AC administered by this schedule lacked antitumor activity in patients with advanced colorectal carcinomas.
Pazdur
R
R
Division of Medicine, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Medgyesy
D C
DC
Winn
R J
RJ
Dakhil
S R
SR
Moore
D F
DF
Scalzo
A
A
Hoff
P M
PM
Arbuck
S G
SG
Abbruzzese
J L
JL
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009362:Neoplasm Metastasis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C080125:9-aminocamptothecin; D002166:Camptothecin