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

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

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / radiotherapy*
  • Animals
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / radiotherapy*
  • Combined Modality Therapy
  • Female
  • Heterocyclic Compounds / pharmacokinetics
  • Heterocyclic Compounds / therapeutic use*
  • Humans
  • Mice
  • Mice, Nude
  • Oligopeptides / pharmacokinetics
  • Oligopeptides / therapeutic use*
  • Paclitaxel / therapeutic use*
  • Radioimmunotherapy*
  • Time Factors
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Yttrium / pharmacokinetics
  • Yttrium / therapeutic use*

Substances

  • Antineoplastic Agents, Phytogenic
  • Heterocyclic Compounds
  • Oligopeptides
  • yttrium-90-DOTA-peptide-chimeric L6
  • Yttrium
  • Paclitaxel