Radioimmunotherapy with 111In/90Y-2IT-BAD-m170 for metastatic prostate cancer

Robert T O'Donnell, S. J. DeNardo, A. Yuan, S. Shen, Carol M Richman, Primo N Lara, I. J. Griffith, D. S. Goldstein, D. L. Kukis, G. S. Martinez, G. R. Mirick, Gerald L Denardo, Frederick J Meyers

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Abstract

Purpose: Over 31,000 Americans die of androgen-independent metastatic prostate cancer each year. New strategies that do not involve hormonal manipulation but instead recognize the biochemical and molecular characteristics of prostate cancer are needed. Radioimmunotherapy (RIT) uses a tumor-specific monoclonal antibody to deliver systemic, targeted radiation to cancer. The objectives of this Phase I study of 111In-2IT-BAD-m170 (for imaging) and 90Y-2IT-BAD-m170 (for therapy) were to determine the toxicity and maximum tolerated dose (MTD), the specificity for targeting metastatic prostate cancer, and the efficacy for palliation of pain. Experimental Design: M170 is a mouse monoclonal antibody that targets adenocarcinomas. Patients with adequate renal and liver function, rising prostate-specific antigen, and androgen-independent metastatic prostate cancer were eligible. After estimation of dosimetry and pharmacokinetics with 111In-2IT-BAD-m170, a single dose of 90Y-2IT-BAD-m170 (0.185, 0.370, 0.555, or 0.740 GBq/m2) was administered to cohorts of three patients. Pain was assessed objectively by questionnaires before and for 8 weeks after RIT; weekly prostate-specific antigen levels were obtained for 2 months after RIT. Results: The MTD of 90Y-2IT-BAD-m170 was 0.740 GBq/m2 for patients that had up to 10% of the axial skeleton involved with prostate cancer. Toxicity was almost exclusively confined to reversible myelosuppression. Metastatic prostate cancer was targeted by 111In-2IT-BAD-m170 in all 17 patients. The mean radiation dose delivered to 39 bone and 18 nodal metastases by 90Y-2IT-BAD-m170 was 10.5 Gy/GBq (range 2.8-25.1). Thirteen of 17 patients reported pain before 90Y-2IT-BAD-m170; 7 of these 13 had a partial or complete resolution of pain that lasted an average of 4.3 weeks. Conclusions: This study determined the MTD of 111In/ 90Y-2IT-BAD-m170 in patients with metastatic prostate cancer. The drugs were well tolerated, targeted metastases, and temporarily palliated pain.

Original languageEnglish (US)
Pages (from-to)1561-1568
Number of pages8
JournalClinical Cancer Research
Volume7
Issue number6
StatePublished - 2001

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Radioimmunotherapy
Prostatic Neoplasms
Maximum Tolerated Dose
Pain
Prostate-Specific Antigen
Androgens
Monoclonal Antibodies
Radiation
Neoplasm Metastasis
Skeleton
Neoplasms
Adenocarcinoma
Research Design
Pharmacokinetics
Kidney
Bone and Bones
Liver
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Radioimmunotherapy with 111In/90Y-2IT-BAD-m170 for metastatic prostate cancer. / O'Donnell, Robert T; DeNardo, S. J.; Yuan, A.; Shen, S.; Richman, Carol M; Lara, Primo N; Griffith, I. J.; Goldstein, D. S.; Kukis, D. L.; Martinez, G. S.; Mirick, G. R.; Denardo, Gerald L; Meyers, Frederick J.

In: Clinical Cancer Research, Vol. 7, No. 6, 2001, p. 1561-1568.

Research output: Contribution to journalArticle

O'Donnell, RT, DeNardo, SJ, Yuan, A, Shen, S, Richman, CM, Lara, PN, Griffith, IJ, Goldstein, DS, Kukis, DL, Martinez, GS, Mirick, GR, Denardo, GL & Meyers, FJ 2001, 'Radioimmunotherapy with 111In/90Y-2IT-BAD-m170 for metastatic prostate cancer', Clinical Cancer Research, vol. 7, no. 6, pp. 1561-1568.
O'Donnell, Robert T ; DeNardo, S. J. ; Yuan, A. ; Shen, S. ; Richman, Carol M ; Lara, Primo N ; Griffith, I. J. ; Goldstein, D. S. ; Kukis, D. L. ; Martinez, G. S. ; Mirick, G. R. ; Denardo, Gerald L ; Meyers, Frederick J. / Radioimmunotherapy with 111In/90Y-2IT-BAD-m170 for metastatic prostate cancer. In: Clinical Cancer Research. 2001 ; Vol. 7, No. 6. pp. 1561-1568.
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abstract = "Purpose: Over 31,000 Americans die of androgen-independent metastatic prostate cancer each year. New strategies that do not involve hormonal manipulation but instead recognize the biochemical and molecular characteristics of prostate cancer are needed. Radioimmunotherapy (RIT) uses a tumor-specific monoclonal antibody to deliver systemic, targeted radiation to cancer. The objectives of this Phase I study of 111In-2IT-BAD-m170 (for imaging) and 90Y-2IT-BAD-m170 (for therapy) were to determine the toxicity and maximum tolerated dose (MTD), the specificity for targeting metastatic prostate cancer, and the efficacy for palliation of pain. Experimental Design: M170 is a mouse monoclonal antibody that targets adenocarcinomas. Patients with adequate renal and liver function, rising prostate-specific antigen, and androgen-independent metastatic prostate cancer were eligible. After estimation of dosimetry and pharmacokinetics with 111In-2IT-BAD-m170, a single dose of 90Y-2IT-BAD-m170 (0.185, 0.370, 0.555, or 0.740 GBq/m2) was administered to cohorts of three patients. Pain was assessed objectively by questionnaires before and for 8 weeks after RIT; weekly prostate-specific antigen levels were obtained for 2 months after RIT. Results: The MTD of 90Y-2IT-BAD-m170 was 0.740 GBq/m2 for patients that had up to 10{\%} of the axial skeleton involved with prostate cancer. Toxicity was almost exclusively confined to reversible myelosuppression. Metastatic prostate cancer was targeted by 111In-2IT-BAD-m170 in all 17 patients. The mean radiation dose delivered to 39 bone and 18 nodal metastases by 90Y-2IT-BAD-m170 was 10.5 Gy/GBq (range 2.8-25.1). Thirteen of 17 patients reported pain before 90Y-2IT-BAD-m170; 7 of these 13 had a partial or complete resolution of pain that lasted an average of 4.3 weeks. Conclusions: This study determined the MTD of 111In/ 90Y-2IT-BAD-m170 in patients with metastatic prostate cancer. The drugs were well tolerated, targeted metastases, and temporarily palliated pain.",
author = "O'Donnell, {Robert T} and DeNardo, {S. J.} and A. Yuan and S. Shen and Richman, {Carol M} and Lara, {Primo N} and Griffith, {I. J.} and Goldstein, {D. S.} and Kukis, {D. L.} and Martinez, {G. S.} and Mirick, {G. R.} and Denardo, {Gerald L} and Meyers, {Frederick J}",
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T1 - Radioimmunotherapy with 111In/90Y-2IT-BAD-m170 for metastatic prostate cancer

AU - O'Donnell, Robert T

AU - DeNardo, S. J.

AU - Yuan, A.

AU - Shen, S.

AU - Richman, Carol M

AU - Lara, Primo N

AU - Griffith, I. J.

AU - Goldstein, D. S.

AU - Kukis, D. L.

AU - Martinez, G. S.

AU - Mirick, G. R.

AU - Denardo, Gerald L

AU - Meyers, Frederick J

PY - 2001

Y1 - 2001

N2 - Purpose: Over 31,000 Americans die of androgen-independent metastatic prostate cancer each year. New strategies that do not involve hormonal manipulation but instead recognize the biochemical and molecular characteristics of prostate cancer are needed. Radioimmunotherapy (RIT) uses a tumor-specific monoclonal antibody to deliver systemic, targeted radiation to cancer. The objectives of this Phase I study of 111In-2IT-BAD-m170 (for imaging) and 90Y-2IT-BAD-m170 (for therapy) were to determine the toxicity and maximum tolerated dose (MTD), the specificity for targeting metastatic prostate cancer, and the efficacy for palliation of pain. Experimental Design: M170 is a mouse monoclonal antibody that targets adenocarcinomas. Patients with adequate renal and liver function, rising prostate-specific antigen, and androgen-independent metastatic prostate cancer were eligible. After estimation of dosimetry and pharmacokinetics with 111In-2IT-BAD-m170, a single dose of 90Y-2IT-BAD-m170 (0.185, 0.370, 0.555, or 0.740 GBq/m2) was administered to cohorts of three patients. Pain was assessed objectively by questionnaires before and for 8 weeks after RIT; weekly prostate-specific antigen levels were obtained for 2 months after RIT. Results: The MTD of 90Y-2IT-BAD-m170 was 0.740 GBq/m2 for patients that had up to 10% of the axial skeleton involved with prostate cancer. Toxicity was almost exclusively confined to reversible myelosuppression. Metastatic prostate cancer was targeted by 111In-2IT-BAD-m170 in all 17 patients. The mean radiation dose delivered to 39 bone and 18 nodal metastases by 90Y-2IT-BAD-m170 was 10.5 Gy/GBq (range 2.8-25.1). Thirteen of 17 patients reported pain before 90Y-2IT-BAD-m170; 7 of these 13 had a partial or complete resolution of pain that lasted an average of 4.3 weeks. Conclusions: This study determined the MTD of 111In/ 90Y-2IT-BAD-m170 in patients with metastatic prostate cancer. The drugs were well tolerated, targeted metastases, and temporarily palliated pain.

AB - Purpose: Over 31,000 Americans die of androgen-independent metastatic prostate cancer each year. New strategies that do not involve hormonal manipulation but instead recognize the biochemical and molecular characteristics of prostate cancer are needed. Radioimmunotherapy (RIT) uses a tumor-specific monoclonal antibody to deliver systemic, targeted radiation to cancer. The objectives of this Phase I study of 111In-2IT-BAD-m170 (for imaging) and 90Y-2IT-BAD-m170 (for therapy) were to determine the toxicity and maximum tolerated dose (MTD), the specificity for targeting metastatic prostate cancer, and the efficacy for palliation of pain. Experimental Design: M170 is a mouse monoclonal antibody that targets adenocarcinomas. Patients with adequate renal and liver function, rising prostate-specific antigen, and androgen-independent metastatic prostate cancer were eligible. After estimation of dosimetry and pharmacokinetics with 111In-2IT-BAD-m170, a single dose of 90Y-2IT-BAD-m170 (0.185, 0.370, 0.555, or 0.740 GBq/m2) was administered to cohorts of three patients. Pain was assessed objectively by questionnaires before and for 8 weeks after RIT; weekly prostate-specific antigen levels were obtained for 2 months after RIT. Results: The MTD of 90Y-2IT-BAD-m170 was 0.740 GBq/m2 for patients that had up to 10% of the axial skeleton involved with prostate cancer. Toxicity was almost exclusively confined to reversible myelosuppression. Metastatic prostate cancer was targeted by 111In-2IT-BAD-m170 in all 17 patients. The mean radiation dose delivered to 39 bone and 18 nodal metastases by 90Y-2IT-BAD-m170 was 10.5 Gy/GBq (range 2.8-25.1). Thirteen of 17 patients reported pain before 90Y-2IT-BAD-m170; 7 of these 13 had a partial or complete resolution of pain that lasted an average of 4.3 weeks. Conclusions: This study determined the MTD of 111In/ 90Y-2IT-BAD-m170 in patients with metastatic prostate cancer. The drugs were well tolerated, targeted metastases, and temporarily palliated pain.

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