Importance of temporal relationships in combined modality radioimmunotherapy of breast carcinoma

Sally J. DeNardo, Linda A. Kroger, Kathleen R. Lamborn, Laird A. Miers, Robert T O'Donnell, David L. Kukis, Carol M Richman, Gerald L Denardo

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

BACKGROUND. The beneficial effects of radioimmunotherapy (RIT) may result from activation of molecular pathways that lead to programmed cell death (apoptosis). The influences of sequence and timing of 90Y-DOTA- peptide-ChL6 antibody (90Y-ChL6) and anti-epidermal growth factor receptor antibody (ch225) or paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ) on efficacy and toxicity were examined. METHODS. Groups of human breast carcinoma (HBT 3477) tumored mice received paclitaxel (300 or 600 μg) or ch225 (70, 150, or 350 μg) at various intervals before or after 90Y-ChL6. Mortality, hematologic toxicity, weight loss, and therapeutic efficacy were evaluated. RESULTS. Mice receiving paclitaxel within 24 hours of 90Y-ChL6 had a 100% response rate; 48% were cured when paclitaxel was given 6 or 24 hours after 90Y-ChL6. When 150 μg ch225 was given 24 hours before 90Y-ChL6, the response and cure rates surpassed those of 90Y-ChL6 alone. Timing of administration was critical, with mortality rates as high as 80% in some groups receiving 350 μg ch225 and 90Y-ChL6. CONCLUSIONS. In this aggressive human breast carcinoma model, combined 90Y-ChL6 and paclitaxel had a high therapeutic index with many cures. Sequence of administration was critical in order for ch225 or paclitaxel, when combined with 90Y-ChL6, to enhance the response rate.

Original languageEnglish (US)
Pages (from-to)2583-2590
Number of pages8
JournalCancer
Volume80
Issue number12 SUPPL.
StatePublished - Dec 15 1997

Keywords

  • Antibody
  • Breast carcinoma
  • Ch225
  • Paclitaxel
  • Radioimmunoconjugate therapy
  • Yttrium-90

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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