Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil®): Possible role in hypersensitivity reactions

Asher Chanan-Khan, J. Szebeni, S. Savay, L. Liebes, N. M. Rafique, C. R. Alving, F. M. Muggia

Research output: Contribution to journalArticle

287 Scopus citations

Abstract

Background: Pegylated liposomal doxorubicin (Doxil®) has been reported to cause immediate hypersensitivity reactions (HSRs) that cannot be explained as IgE-mediated (type I) allergy. Previous in vitro and animal studies indicated that activation of the complement (C) system might play a causal role in the process, a proposal that has not been tested in humans to date. Patients and methods: Patients with solid tumors (n = 29) treated for the first time with Doxil were evaluated for HSRs and concurrent C activation. HSRs were classified from mild to severe, while C activation was estimated by serial measurement of plasma C terminal complex (SC5b-9) levels. Increases in SC5b-9 were compared in patients with or without reactions, and were correlated with Doxil dose rate. Results: Moderate to severe HSRs occurred in 45% of patients. Plasma SC5b-9 at 10 min after infusion was significantly elevated in 92% of reactor patients versus 56% in the non-reactor group, and the rise was greater in reactors than in non-reactors. We found significant association between C activation and HSRs, both showing direct correlation with the initial Doxil dose rate. Conclusions: C activation may play a key role in HSRs to Doxil. However, low-level C activation does not necessarily entail clinical symptoms, highlighting the probable involvement of further, as yet unidentified, amplification factors.

Original languageEnglish (US)
Pages (from-to)1430-1437
Number of pages8
JournalAnnals of Oncology
Volume14
Issue number9
DOIs
StatePublished - Sep 1 2003

Keywords

  • Allergy
  • Anaphylatoxins
  • Cancer chemotherapy
  • Doxorubicin
  • Hypersensitivity reactions
  • Liposomes

ASJC Scopus subject areas

  • Hematology
  • Oncology

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