Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel

An in vitro study

J. Szebeni, Franco M. Muggia, Carl R. Alving

Research output: Contribution to journalArticle

267 Citations (Scopus)

Abstract

Background: Cancer patients treated with the anticancer drug, paclitaxel (Taxol) often experience mild to severe hypersensitivity reactions. It is not known how these reactions are induced and whether the inducer is paclitaxel or its vehicle (i.e., Cremophor EL in 50% ethanol). Molecules present in Cremophor EL are similar in structure to certain nonionic block copolymers that activate complement proteins (i.e., proteins involved in various immune processes). To explore the role of complement in the observed hypersensitivity reactions, we studied the effects of paclitaxel and Cremophor EL plus ethanol on human complement in vitro. Methods: Serum specimens from healthy individuals and cancer patients were incubated with paclitaxel or with relevant control compounds (Cremophor EL with ethanol, ethanol only, docetaxel, and cyclosporine), and markers of complement activation (SC5b-9 and Bb) were measured by enzyme-linked immunosorbent assay. Similar incubations were performed in the presence of inhibitors of complement activation (i.e., EGTA/Mg2+ and soluble complement receptor type 1 [sCR1]). Results: Paclitaxel in Cremophor EL plus ethanol caused increased formation of SC5b-9 in serum specimens from 10 of 10 healthy control subjects and from five of 10 cancer patients. Experiments with one or more individual sera indicated the above effect was due to Cremophor EL plus ethanol, that increased formation of Bb also occurred, that the drug-induced rise in SC5b- 9 was inhibited by sCR1, and that EGTA/Mg2+ partially inhibited SC5b-9 formation and stimulated Bb formation. Implication: The role of complement activation in hypersensitivity reactions associated with administration of paclitaxel in Cremophor EL plus ethanol should be studied in vivo.

Original languageEnglish
Pages (from-to)300-306
Number of pages7
JournalJournal of the National Cancer Institute
Volume90
Issue number4
Publication statusPublished - Feb 18 1998

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Complement Activation
Paclitaxel
Hypersensitivity
Ethanol
Complement Receptors
Egtazic Acid
docetaxel
Serum
Neoplasms
cremophor EL
In Vitro Techniques
Pharmaceutical Preparations
Cyclosporine
Healthy Volunteers
Complement System Proteins
Enzyme-Linked Immunosorbent Assay
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel : An in vitro study. / Szebeni, J.; Muggia, Franco M.; Alving, Carl R.

In: Journal of the National Cancer Institute, Vol. 90, No. 4, 18.02.1998, p. 300-306.

Research output: Contribution to journalArticle

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