title: Phase II trial of 9-aminocamptothecin (NSC 603071) administered as a 120-hr continuous infusion weekly for three weeks in metastatic colorectal carcinoma.
abstract: 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.
authors.affiliation: Division of Medicine, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pazdur
authors.forename: D C
authors.initials: DC
authors.lastname: Medgyesy
authors.forename: R J
authors.initials: RJ
authors.lastname: Winn
authors.forename: S R
authors.initials: SR
authors.lastname: Dakhil
authors.forename: D F
authors.initials: DF
authors.lastname: Moore
authors.forename: A
authors.initials: A
authors.lastname: Scalzo
authors.forename: P M
authors.initials: PM
authors.lastname: Hoff
authors.forename: S G
authors.initials: SG
authors.lastname: Arbuck
authors.forename: J L
authors.initials: JL
authors.lastname: Abbruzzese
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; C080125:9-aminocamptothecin; D002166:Camptothecin