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Phase II trial of echinomycin in patients with advanced or recurrent colorectal cancer

Abstract

Echinomycin is a novel bifunctional intercalating agent derived fromStreptomyces 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 in 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 21-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.

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Wadler, S., Tenteromano, L., Cazenave, L. et al. Phase II trial of echinomycin in patients with advanced or recurrent colorectal cancer. Cancer Chemother. Pharmacol. 34, 266–269 (1994). https://doi.org/10.1007/BF00685088

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Key words

  • Echinomycin
  • Colorectal cancer
  • Phase II