Synergistic therapy of breast cancer with Y90-chimeric L6 and paclitaxel in the xenografted mouse model: Development of a clinical protocol

Sally J. DeNardo, Carol M. Richman, David L. Kukis, Sui Shen, Kathleen R. Lamborn, Laird A. Miers, Linda A. Kroger, Edith A. Perez, Gerald L. Denardo

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 RlT alone, were examined. Materials and Methods. Mice bearing human breast cancer xenografts (HBT 3477) received i.v. Y-90-DOTA-peptide-ChL6 (260 μCi), and i.p. Taxol (300 or 600 μg) 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 μg Taxol 48 hours after RlT 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.

Original languageEnglish (US)
Pages (from-to)4011-4018
Number of pages8
JournalAnticancer Research
Volume18
Issue number6 A
StatePublished - 1998

Fingerprint

Radioimmunotherapy
Clinical Protocols
Paclitaxel
Breast Neoplasms
Therapeutics
Bone Marrow
Neoplasms
Clinical Trials
Radiation
Heterografts
Peptides

Keywords

  • Breast cancer
  • Paclitaxel
  • Radioimmunotherapy
  • Taxol
  • Yttrium-90

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

DeNardo, S. J., Richman, C. M., Kukis, D. L., Shen, S., Lamborn, K. R., Miers, L. A., ... Denardo, G. L. (1998). Synergistic therapy of breast cancer with Y90-chimeric L6 and paclitaxel in the xenografted mouse model: Development of a clinical protocol. Anticancer Research, 18(6 A), 4011-4018.

Synergistic therapy of breast cancer with Y90-chimeric L6 and paclitaxel in the xenografted mouse model : Development of a clinical protocol. / DeNardo, Sally J.; Richman, Carol M.; Kukis, David L.; Shen, Sui; Lamborn, Kathleen R.; Miers, Laird A.; Kroger, Linda A.; Perez, Edith A.; Denardo, Gerald L.

In: Anticancer Research, Vol. 18, No. 6 A, 1998, p. 4011-4018.

Research output: Contribution to journalArticle

DeNardo, SJ, Richman, CM, Kukis, DL, Shen, S, Lamborn, KR, Miers, LA, Kroger, LA, Perez, EA & Denardo, GL 1998, 'Synergistic therapy of breast cancer with Y90-chimeric L6 and paclitaxel in the xenografted mouse model: Development of a clinical protocol', Anticancer Research, vol. 18, no. 6 A, pp. 4011-4018.
DeNardo, Sally J. ; Richman, Carol M. ; Kukis, David L. ; Shen, Sui ; Lamborn, Kathleen R. ; Miers, Laird A. ; Kroger, Linda A. ; Perez, Edith A. ; Denardo, Gerald L. / Synergistic therapy of breast cancer with Y90-chimeric L6 and paclitaxel in the xenografted mouse model : Development of a clinical protocol. In: Anticancer Research. 1998 ; Vol. 18, No. 6 A. pp. 4011-4018.
@article{083e16de8df94470b218af5eeb045fa0,
title = "Synergistic therapy of breast cancer with Y90-chimeric L6 and paclitaxel in the xenografted mouse model: Development of a clinical protocol",
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 RlT alone, were examined. Materials and Methods. Mice bearing human breast cancer xenografts (HBT 3477) received i.v. Y-90-DOTA-peptide-ChL6 (260 μCi), and i.p. Taxol (300 or 600 μg) 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 μg Taxol 48 hours after RlT 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.",
keywords = "Breast cancer, Paclitaxel, Radioimmunotherapy, Taxol, Yttrium-90",
author = "DeNardo, {Sally J.} and Richman, {Carol M.} and Kukis, {David L.} and Sui Shen and Lamborn, {Kathleen R.} and Miers, {Laird A.} and Kroger, {Linda A.} and Perez, {Edith A.} and Denardo, {Gerald L.}",
year = "1998",
language = "English (US)",
volume = "18",
pages = "4011--4018",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "6 A",

}

TY - JOUR

T1 - Synergistic therapy of breast cancer with Y90-chimeric L6 and paclitaxel in the xenografted mouse model

T2 - Development of a clinical protocol

AU - DeNardo, Sally J.

AU - Richman, Carol M.

AU - Kukis, David L.

AU - Shen, Sui

AU - Lamborn, Kathleen R.

AU - Miers, Laird A.

AU - Kroger, Linda A.

AU - Perez, Edith A.

AU - Denardo, Gerald L.

PY - 1998

Y1 - 1998

N2 - 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 RlT alone, were examined. Materials and Methods. Mice bearing human breast cancer xenografts (HBT 3477) received i.v. Y-90-DOTA-peptide-ChL6 (260 μCi), and i.p. Taxol (300 or 600 μg) 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 μg Taxol 48 hours after RlT 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.

AB - 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 RlT alone, were examined. Materials and Methods. Mice bearing human breast cancer xenografts (HBT 3477) received i.v. Y-90-DOTA-peptide-ChL6 (260 μCi), and i.p. Taxol (300 or 600 μg) 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 μg Taxol 48 hours after RlT 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.

KW - Breast cancer

KW - Paclitaxel

KW - Radioimmunotherapy

KW - Taxol

KW - Yttrium-90

UR - http://www.scopus.com/inward/record.url?scp=0032423412&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032423412&partnerID=8YFLogxK

M3 - Article

C2 - 9891439

AN - SCOPUS:0032423412

VL - 18

SP - 4011

EP - 4018

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 6 A

ER -