title: Phase II trial of echinomycin in patients with advanced or recurrent colorectal cancer.
abstract: Echinomycin is a novel bifunctional intercalating agent derived from Streptomyces echinatus. A phase II clinical trial of echinomycin in patients with advanced, measurable colorectal cancer was initiated to determine the efficacy and toxicities of this agent. Echinomycin, 1.5 mg/m2, was given initially as a 30- to 60-min infusion every 4 weeks. After 4 episodes of anaphylaxis had occurred among the first 14 patients, the schedule was changed to a 24-h infusion, and an additional 16 patients were treated on this schedule. Treatment was given every 3 weeks. A total of 30 patients were eligible and evaluable; there were 3 (10%; 90% confidence interval, 3%-23%) clinical responses lasting 3, 3+, and 12 months, respectively. The most serious toxicity encountered was anaphylaxis, which occurred in 5 patients, although with no serious sequelae. A premedication regimen with dexamethasone, diphenhydramine, and cimetidine and a change of the duration of the infusion to 24 h reduced the incidence of this complication. Grade 2-3 vomiting occurred among earlier patients treated; however, with the 24-h schedule this toxicity was substantially reduced. The sole important case of hematologic toxicity was a single patient with grade 3 thrombocytopenia. Echinomycin employed in this dose and schedule had modest activity against colorectal cancer, comparable with that observed with 5-fluorouracil. Further studies in patients with gastrointestinal malignancies using a 24-h infusion with a dexamethasone premedication regimen similar to that employed prior to administration of taxol may be warranted.
authors.affiliation: Department of Oncology, Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, New York 10467.
authors.forename: S
authors.initials: S
authors.lastname: Wadler
authors.forename: L
authors.initials: L
authors.lastname: Tenteromano
authors.forename: L
authors.initials: L
authors.lastname: Cazenave
authors.forename: J A
authors.initials: JA
authors.lastname: Sparano
authors.forename: E S
authors.initials: ES
authors.lastname: Greenwald
authors.forename: A
authors.initials: A
authors.lastname: Rozenblit
authors.forename: R
authors.initials: R
authors.lastname: Kaleya
authors.forename: P H
authors.initials: PH
authors.lastname: Wiernik
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004448:Echinomycin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D004448:Echinomycin