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

Scott Wadler, Laura Tenteromano, Lorraine Cazenave, Joseph A. Sparano, Edward S. Greenwald, Alla Rozenblit, Ronald Kaleya, Peter H. Wiernik

Research output: Contribution to journalArticle

28 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)266-269
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume34
Issue number3
DOIs
StatePublished - May 1 1994

Keywords

  • Colorectal cancer
  • Echinomycin
  • Phase II

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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    Wadler, S., Tenteromano, L., Cazenave, L., Sparano, J. A., Greenwald, E. S., Rozenblit, A., Kaleya, R., & Wiernik, P. H. (1994). Phase II trial of echinomycin in patients with advanced or recurrent colorectal cancer. Cancer Chemotherapy and Pharmacology, 34(3), 266-269. https://doi.org/10.1007/BF00685088