Does paclitaxel (taxol) given after111In-labeled monoclonal antibodies increase tumor-cumulated activity in epithelial cancers?

Laird Miers, Kathleen Lamborn, Aina Yuan, Carol M Richman, Arutselvan Natarajan, Sally DeNardo, Gerald L Denardo

Research output: Contribution to journalArticle

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Abstract

Purpose: Paclitaxel synergized radiolabeled monoclonal antibodies, enhancing therapeutic effect in studies in mice with human xenografts. Paclitaxel was also observed to increase tumor uptake in imaging studies of 111In-DOTA-Gly3Phe-m170 in patients with breast and prostate cancers. Further evaluations of tissue-cumulated activities, therapeutic indices, and pharmacokinetics were done using data for patients with breast and prostate cancer and for mice with human breast cancer xenografts. Experimental Design: In radioimmunotherapy trials, 12 patients with breast or prostate cancer were given two imaging doses (5 mCi each) of 111In-DOTA-GlysPhe-m170 1 week apart. Five of these patients were given a single dose of paclitaxel i.v. (75 mg/m2) 2 days after the second dose of 111In. In a subsequent study, athymic mice with human breast cancer xenografts were given 111In-DOTA-Gly 3Phe-ChL6 alone, or in combination with daily paclitaxel i.p. (300 μg) one or more times. Pharmacokinetics were studied for at least 6 days in patients and 5 days in mice. Cumulated activities were determined for tumors and normal tissues. Results: Tumor-cumulated activity for every patient in the paclitaxel-treated group increased for the second dose of 111In-DOTA- Gly3Phe-m170. The median ratio of cumulated activities in tumors for imaging dose 2 to those for dose 1 was 1.0 (0.8-1.3) in patients that were not given paclitaxel and 1.3 (1.2-1.4) in patients given paclitaxel. Normal tissue-cumulated activities were not different for the two doses. Mice given paclitaxel 1 day after 111In-DOTA-Gly3Phe-ChL6 also showed an increase in tumor-cumulated activity, 22.9 (± 1.3) versus 19.4 (± 3.3) μCi h/g/μCi (P = 0.05). Cumulated activities of normal tissues were similar for all groups of mice. Conclusions: Paclitaxel given 1 to 2 days after 111In-DOTA-Gly3Phe-monoclonal antibody increased the tumor-cumulated activity in patients and in mice with epithelial cancers and did not alter cumulated activities in normal tissues.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume11
Issue number19 II
DOIs
StatePublished - Oct 1 2005

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Paclitaxel
Monoclonal Antibodies
Neoplasms
Breast Neoplasms
Heterografts
Prostatic Neoplasms
Pharmacokinetics
Radioimmunotherapy
Therapeutic Uses
Nude Mice
indium-111-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Does paclitaxel (taxol) given after111In-labeled monoclonal antibodies increase tumor-cumulated activity in epithelial cancers? / Miers, Laird; Lamborn, Kathleen; Yuan, Aina; Richman, Carol M; Natarajan, Arutselvan; DeNardo, Sally; Denardo, Gerald L.

In: Clinical Cancer Research, Vol. 11, No. 19 II, 01.10.2005.

Research output: Contribution to journalArticle

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title = "Does paclitaxel (taxol) given after111In-labeled monoclonal antibodies increase tumor-cumulated activity in epithelial cancers?",
abstract = "Purpose: Paclitaxel synergized radiolabeled monoclonal antibodies, enhancing therapeutic effect in studies in mice with human xenografts. Paclitaxel was also observed to increase tumor uptake in imaging studies of 111In-DOTA-Gly3Phe-m170 in patients with breast and prostate cancers. Further evaluations of tissue-cumulated activities, therapeutic indices, and pharmacokinetics were done using data for patients with breast and prostate cancer and for mice with human breast cancer xenografts. Experimental Design: In radioimmunotherapy trials, 12 patients with breast or prostate cancer were given two imaging doses (5 mCi each) of 111In-DOTA-GlysPhe-m170 1 week apart. Five of these patients were given a single dose of paclitaxel i.v. (75 mg/m2) 2 days after the second dose of 111In. In a subsequent study, athymic mice with human breast cancer xenografts were given 111In-DOTA-Gly 3Phe-ChL6 alone, or in combination with daily paclitaxel i.p. (300 μg) one or more times. Pharmacokinetics were studied for at least 6 days in patients and 5 days in mice. Cumulated activities were determined for tumors and normal tissues. Results: Tumor-cumulated activity for every patient in the paclitaxel-treated group increased for the second dose of 111In-DOTA- Gly3Phe-m170. The median ratio of cumulated activities in tumors for imaging dose 2 to those for dose 1 was 1.0 (0.8-1.3) in patients that were not given paclitaxel and 1.3 (1.2-1.4) in patients given paclitaxel. Normal tissue-cumulated activities were not different for the two doses. Mice given paclitaxel 1 day after 111In-DOTA-Gly3Phe-ChL6 also showed an increase in tumor-cumulated activity, 22.9 (± 1.3) versus 19.4 (± 3.3) μCi h/g/μCi (P = 0.05). Cumulated activities of normal tissues were similar for all groups of mice. Conclusions: Paclitaxel given 1 to 2 days after 111In-DOTA-Gly3Phe-monoclonal antibody increased the tumor-cumulated activity in patients and in mice with epithelial cancers and did not alter cumulated activities in normal tissues.",
author = "Laird Miers and Kathleen Lamborn and Aina Yuan and Richman, {Carol M} and Arutselvan Natarajan and Sally DeNardo and Denardo, {Gerald L}",
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T1 - Does paclitaxel (taxol) given after111In-labeled monoclonal antibodies increase tumor-cumulated activity in epithelial cancers?

AU - Miers, Laird

AU - Lamborn, Kathleen

AU - Yuan, Aina

AU - Richman, Carol M

AU - Natarajan, Arutselvan

AU - DeNardo, Sally

AU - Denardo, Gerald L

PY - 2005/10/1

Y1 - 2005/10/1

N2 - Purpose: Paclitaxel synergized radiolabeled monoclonal antibodies, enhancing therapeutic effect in studies in mice with human xenografts. Paclitaxel was also observed to increase tumor uptake in imaging studies of 111In-DOTA-Gly3Phe-m170 in patients with breast and prostate cancers. Further evaluations of tissue-cumulated activities, therapeutic indices, and pharmacokinetics were done using data for patients with breast and prostate cancer and for mice with human breast cancer xenografts. Experimental Design: In radioimmunotherapy trials, 12 patients with breast or prostate cancer were given two imaging doses (5 mCi each) of 111In-DOTA-GlysPhe-m170 1 week apart. Five of these patients were given a single dose of paclitaxel i.v. (75 mg/m2) 2 days after the second dose of 111In. In a subsequent study, athymic mice with human breast cancer xenografts were given 111In-DOTA-Gly 3Phe-ChL6 alone, or in combination with daily paclitaxel i.p. (300 μg) one or more times. Pharmacokinetics were studied for at least 6 days in patients and 5 days in mice. Cumulated activities were determined for tumors and normal tissues. Results: Tumor-cumulated activity for every patient in the paclitaxel-treated group increased for the second dose of 111In-DOTA- Gly3Phe-m170. The median ratio of cumulated activities in tumors for imaging dose 2 to those for dose 1 was 1.0 (0.8-1.3) in patients that were not given paclitaxel and 1.3 (1.2-1.4) in patients given paclitaxel. Normal tissue-cumulated activities were not different for the two doses. Mice given paclitaxel 1 day after 111In-DOTA-Gly3Phe-ChL6 also showed an increase in tumor-cumulated activity, 22.9 (± 1.3) versus 19.4 (± 3.3) μCi h/g/μCi (P = 0.05). Cumulated activities of normal tissues were similar for all groups of mice. Conclusions: Paclitaxel given 1 to 2 days after 111In-DOTA-Gly3Phe-monoclonal antibody increased the tumor-cumulated activity in patients and in mice with epithelial cancers and did not alter cumulated activities in normal tissues.

AB - Purpose: Paclitaxel synergized radiolabeled monoclonal antibodies, enhancing therapeutic effect in studies in mice with human xenografts. Paclitaxel was also observed to increase tumor uptake in imaging studies of 111In-DOTA-Gly3Phe-m170 in patients with breast and prostate cancers. Further evaluations of tissue-cumulated activities, therapeutic indices, and pharmacokinetics were done using data for patients with breast and prostate cancer and for mice with human breast cancer xenografts. Experimental Design: In radioimmunotherapy trials, 12 patients with breast or prostate cancer were given two imaging doses (5 mCi each) of 111In-DOTA-GlysPhe-m170 1 week apart. Five of these patients were given a single dose of paclitaxel i.v. (75 mg/m2) 2 days after the second dose of 111In. In a subsequent study, athymic mice with human breast cancer xenografts were given 111In-DOTA-Gly 3Phe-ChL6 alone, or in combination with daily paclitaxel i.p. (300 μg) one or more times. Pharmacokinetics were studied for at least 6 days in patients and 5 days in mice. Cumulated activities were determined for tumors and normal tissues. Results: Tumor-cumulated activity for every patient in the paclitaxel-treated group increased for the second dose of 111In-DOTA- Gly3Phe-m170. The median ratio of cumulated activities in tumors for imaging dose 2 to those for dose 1 was 1.0 (0.8-1.3) in patients that were not given paclitaxel and 1.3 (1.2-1.4) in patients given paclitaxel. Normal tissue-cumulated activities were not different for the two doses. Mice given paclitaxel 1 day after 111In-DOTA-Gly3Phe-ChL6 also showed an increase in tumor-cumulated activity, 22.9 (± 1.3) versus 19.4 (± 3.3) μCi h/g/μCi (P = 0.05). Cumulated activities of normal tissues were similar for all groups of mice. Conclusions: Paclitaxel given 1 to 2 days after 111In-DOTA-Gly3Phe-monoclonal antibody increased the tumor-cumulated activity in patients and in mice with epithelial cancers and did not alter cumulated activities in normal tissues.

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