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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52 Scopus citations

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    O'Donnell, R. T., DeNardo, S. J., Yuan, A., Shen, S., Richman, C. M., Lara, P. N., Griffith, I. J., Goldstein, D. S., Kukis, D. L., Martinez, G. S., Mirick, G. R., Denardo, G. L., & Meyers, F. J. (2001). Radioimmunotherapy with 111In/90Y-2IT-BAD-m170 for metastatic prostate cancer. Clinical Cancer Research, 7(6), 1561-1568.