title: Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma.
abstract: OBJECTIVE
  The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, was selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents. We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma.
  
  
  METHODS
  Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days). Patients were assessed for response after two courses.
  
  
  RESULTS
  Seventeen patients with metastatic colorectal cancer were entered onto this trial. No complete or partial responses were noted. Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute granulocyte count (AGC) was 1,500/microL. The median number of courses given was two and the median time to disease progression was 8 weeks.
  
  
  CONCLUSIONS
  At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer. 9-AC infusion schedules of longer duration are currently being investigated in this disease.
authors.affiliation: Department of Gastrointestinal Medical Oncology and Digestive Diseases, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. rpazdur@notes.mdacc.tmc.edu
authors.forename: R
authors.initials: R
authors.lastname: Pazdur
authors.forename: E
authors.initials: E
authors.lastname: Diaz-Canton
authors.forename: W P
authors.initials: WP
authors.lastname: Ballard
authors.forename: J E
authors.initials: JE
authors.lastname: Bradof
authors.forename: S
authors.initials: S
authors.lastname: Graham
authors.forename: S G
authors.initials: SG
authors.lastname: Arbuck
authors.forename: J L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: R
authors.initials: R
authors.lastname: Winn
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000473:pathology*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged
chemical_list: D000970:Antineoplastic Agents; C080125:9-aminocamptothecin; D002166:Camptothecin