In vitro schedule-dependency of myelotoxicity and cytotoxicity of Ecteinascidin 743 (ET-743)

M. Ghielmini, E. Colli, E. Erba, D. Bergamaschi, S. Pampallona, J. Jimeno, G. Faircloth, C. Sessa

Research output: Contribution to journalArticle

Abstract

Background: Ecteinascidin (ET-743) is a marine derived compound with an interesting preclinical profile currently completing phase I clinical trials. The present study was under-taken to compare the toxicity of different schedules of ET-743 against human hemopoietic progenitors and tumour cell lines. Materials and methods: Human hemopoietic progenitors and solid tumour cell lines were incubated with ET-743 for one hour, 24 hours and one hour daily for five consecutive days to define by comparison an 'in vitro therapeutic index'. Additional experiments were set up to assess whether incubation for 24 hours or five days could change either the sensitivity of cells or the activity of ET-743. Results: Prolonged or repeated exposures were more toxic than a single one hour exposure (P <0.001), but due to the higher sensitivity to prolonged exposure of several tumor cell lines, prolonged treatment yielded a more favorable in vitro therapeutic index. After incubation for 24 hours, ET-743 showed a significantly (P <0.01) lower inhibiting capacity. Incubation before treatment rendered progenitors more resistant, but incubation after treatment increased their sensitivity, so that overall the toxicity of ET-743 on hemopoietic cells appears to be close to AUC dependency. Conclusions: Despite the possible effect of some experimental artefacts, prolonged exposure could represent the best schedule of administration of ET- 743.

Original languageEnglish
Pages (from-to)989-993
Number of pages5
JournalAnnals of Oncology
Volume9
Issue number9
DOIs
Publication statusPublished - Sep 1998

Keywords

  • Cell lines
  • Ecteinascidin
  • Hematotoxicology
  • In vitro assays

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ghielmini, M., Colli, E., Erba, E., Bergamaschi, D., Pampallona, S., Jimeno, J., Faircloth, G., & Sessa, C. (1998). In vitro schedule-dependency of myelotoxicity and cytotoxicity of Ecteinascidin 743 (ET-743). Annals of Oncology, 9(9), 989-993. https://doi.org/10.1023/A:1008430827281