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Anticancer Res. 1998 Nov-Dec;18(6A):4011-8.

Synergistic therapy of breast cancer with Y-90-chimeric L6 and paclitaxel in the xenografted mouse model: development of a clinical protocol.

Author information

1
Section of Radiodiagnosis and Therapy, University of California Davis Medical Center, Sacramento, USA.

Abstract

BACKGROUND:

Paclitaxel (Taxol) has demonstrated synergistic enhancement of radioimmunotherapy (RIT) of breast cancer with Y-90 labeled antibody ChL6, in the xenografted mouse model. To determine the optimal sequence and timing of RIT and Taxol for a prospective clinical trial, efficacy and dosimetry in mice, and dosimetry in patients receiving RIT alone, were examined.

MATERIALS AND METHODS:

Mice bearing human breast cancer xenografts (HBT 3477) received i.v. Y-90-DOTA-peptide-ChL6 (260 microCi), and i.p. Taxol (300 or 600 micrograms) 72, 48, or 24 hours prior to RIT, or 6, 24, 48, or 72 hours after RIT.

RESULTS:

Taxol after RIT resulted in cure, CR, or PR of all mice (70/70 tumors) and demonstrated greater therapeutic enhancement (p = 0.001) than Taxol before RIT. Mice receiving 600 micrograms Taxol 48 hours after RIT achieved 88% cure (7/8 tumors). In mice, 57% and 42% of the radiation dose to tumor and marrow, respectively, was delivered from 48-336 hours after RIT; in patients receiving 90Y-DOTA-peptide-ChL6, the corresponding values were 56% and 22%.

CONCLUSIONS:

Taxol given approximately 48 hours after RIT provides coincident peak deposition of Taxol and Y-90 in tumor, and no Taxol in the marrow during the major radiation dose to marrow, resulting in therapeutic enhancement without observable additive toxicity. A clinical trial of low dose Taxol given after RIT to patients with metastatic breast cancer is planned.

PMID:
9891439
[Indexed for MEDLINE]

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