title: Phase II trial of amonafide in advanced colorectal cancer: a SouthWest Oncology Group study.
abstract: Amonafide is a substituted benzisoquinolinedione that exerts its cytotoxicity through effects on macromolecular synthesis and intercalation of DNA. In this trial, 44 patients with advanced colorectal cancer and without prior chemotherapy received amonafide at a starting dose of 300 mg/m2 intravenously over one hour, on a daily x 5 schedule every 3 weeks. Toxicities of grade 3 or above included granulocytopenia, thrombocytopenia, sepsis, anaphylaxis and transient aphasia. Forty-seven % of patients had grade 3 or higher toxicity of any type. There were no complete or partial responses for an overall response rate of 0%, with a 95% confidence interval of 0-9%. The level of toxicity observed on this trial suggests an appropriate dose intensity of amonafide, despite lack of knowledge of patients' acetylator phenotypes.
authors.affiliation: Duke University Medical Center, Durham, NC 27710.
authors.forename: T D
authors.initials: TD
authors.lastname: Brown
authors.forename: P J
authors.initials: PJ
authors.lastname: Goodman
authors.forename: T
authors.initials: T
authors.lastname: Fleming
authors.forename: J S
authors.initials: JS
authors.lastname: Macdonald
authors.forename: J B
authors.initials: JB
authors.lastname: Craig
authors.forename: A B
authors.initials: AB
authors.lastname: Einstein
mesh_terms: D000225:Adenine; D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007094:Imides; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D053644:Naphthalimides; D063065:Organophosphonates
chemical_list: D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; D063065:Organophosphonates; C037020:amonafide; D000225:Adenine