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Importance of temporal relationships in combined modality radioimmunotherapy of breast carcinoma
Author(s) -
DeNardo Sally J.,
Kroger Linda A.,
Lamborn Kathleen R.,
Miers Laird A.,
O'Donnell Robert T.,
Kukis David L.,
Richman Carol M.,
DeNardo Gerald L.
Publication year - 1997
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19971215)80:12+<2583::aid-cncr34>3.0.co;2-6
Subject(s) - radioimmunotherapy , medicine , paclitaxel , toxicity , oncology , breast carcinoma , chemotherapy , antibody , breast cancer , immunology , cancer , monoclonal antibody
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 90 Y‐DOTA‐peptide‐ChL6 antibody ( 90 Y‐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 90 Y‐ChL6. Mortality, hematologic toxicity, weight loss, and therapeutic efficacy were evaluated. RESULTS Mice receiving paclitaxel within 24 hours of 90 Y‐ChL6 had a 100% response rate; 48% were cured when paclitaxel was given 6 or 24 hours after 90 Y‐ChL6. When 150 μg ch225 was given 24 hours before 90 Y‐ChL6, the response and cure rates surpassed those of 90 Y‐ChL6 alone. Timing of administration was critical, with mortality rates as high as 80% in some groups receiving 350 μg ch225 and 90 Y‐ChL6. CONCLUSIONS In this aggressive human breast carcinoma model, combined 90 Y‐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 90 Y‐ChL6, to enhance the response rate. Cancer 1997; 80:2583‐90. © 1997 American Cancer Society.