Radioimmunotherapy with 111in/90y-2it-BAD-m170 for metastatic prostate cancer

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 111 In-2IT-BAD-m170 (for imaging) and 90 Y-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 111 In-2IT-BAD-m170, a single dose of 90 Y-2IT-BAD-m170 (0.185, 0.370, 0.555, or 0.740 GBq/m 2 ) 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 90 Y-2IT-BAD-m170 was 0.740 GBq/m 2 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 111 In-2IT-BAD-m170 in all 17 patients. The mean radiation dose delivered to 39 bone and 18 nodal metastases by 90 Y-2IT-BAD-m170 was 10.5 Gy/GBq (range 2.8–25.1). Thirteen of 17 patients reported pain before 90 Y-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 111 In/ 90 Y-2IT-BAD-m170 in patients with metastatic prostate cancer. The drugs were well tolerated, targeted metastases, and temporarily palliated pain.

[1]  G. Denardo,et al.  Radiation dosimetry for 90Y-2IT-BAD-Lym-1 extrapolated from pharmacokinetics using 111In-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[2]  M. Juweid,et al.  Initial experience with high-dose radioimmunotherapy of metastatic medullary thyroid cancer using 131I-MN-14 F(ab)2 anti-carcinoembryonic antigen MAb and AHSCR. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[3]  Taylor Murray,et al.  Cancer statistics, 2000 , 2000, CA: a cancer journal for clinicians.

[4]  P. Gumerlock,et al.  Molecular biology of prostate carcinogenesis. , 1999, Critical reviews in oncology/hematology.

[5]  G. Denardo,et al.  Dosimetry-based therapy in metastatic breast cancer patients using 90Y monoclonal antibody 170H.82 with autologous stem cell support and cyclosporin A. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[6]  G. Denardo,et al.  67Cu-2IT-BAT-Lym-1 pharmacokinetics, radiation dosimetry, toxicity and tumor regression in patients with lymphoma. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[7]  G. Denardo,et al.  Optimized conditions for chelation of yttrium-90-DOTA immunoconjugates. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  Manyak.  Clinical Applications of Radioimmunoscintigraphy With Prostate-Specific Antibodies for Prostate Cancer. , 1998, Cancer control : journal of the Moffitt Cancer Center.

[9]  F Regan,et al.  Indium-111 capromab pendetide (ProstaScint) imaging to detect recurrent and metastatic prostate cancer. , 1998, Clinical nuclear medicine.

[10]  G. Denardo,et al.  Maximum tolerated dose of 67Cu-2IT-BAT-LYM-1 for fractionated radioimmunotherapy of non-Hodgkin's lymphoma: a pilot study. , 1998, Anticancer research.

[11]  S. Larson,et al.  Interferon-gamma and monoclonal antibody 131I-labeled CC49: outcomes in patients with androgen-independent prostate cancer. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[12]  G. Denardo,et al.  A revolution in the treatment of non-Hodgkin's lymphoma. , 1998, Cancer biotherapy & radiopharmaceuticals.

[13]  G. Denardo,et al.  Prediction of myelotoxicity using radiation doses to marrow from body, blood and marrow sources. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[14]  R. Ceriani,et al.  Radioimmunotherapy for breast cancer using indium-111/yttrium-90 BrE-3: results of a phase I clinical trial. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[15]  K. Lamborn,et al.  Radioimmunotherapy for advanced breast cancer using I-131-ChL6 antibody. , 1997, Anticancer research.

[16]  W. Hawkins,et al.  Patient-specific dosimetry of indium-111- and yttrium-90-labeled monoclonal antibody CC49. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  M. Goris,et al.  Treatment of hormone-refractory prostate cancer with 90Y-CYT-356 monoclonal antibody. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[18]  G. Denardo,et al.  A radioimmunoimaging and MIRD dosimetry treatment planning program for radioimmunotherapy. , 1996, Nuclear medicine and biology.

[19]  G. Denardo,et al.  Antibody responses to macrocycles in lymphoma. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  G. Denardo,et al.  Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[21]  L. Howell,et al.  Immunohistochemical Staining of Metastatic Ductal Carcinomas of the Breast by Monoclonal Antibodies used in Imaging and Therapy: A Comparative Study , 1995, The International journal of biological markers.

[22]  N. Bander.  Current status of monoclonal antibodies for imaging and therapy of prostate cancer. , 1994, Seminars in Oncology.

[23]  J. Schlom,et al.  Treatment of metastatic prostate carcinoma with radiolabeled antibody CC49. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[24]  R. Sylvester,et al.  Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). EORTC GU Group and EORTC Data Center. , 1993, Urology.

[25]  G. Denardo,et al.  Body and blood clearance and marrow radiation dose of 131I-Lym-1 in patients with B-cell malignancies. , 1993, Nuclear medicine communications.

[26]  S. McQuarrie,et al.  MAb 170H.82: an evaluation of a novel panadenocarcinoma monoclonal antibody labelled with 99Tcm and with 111In. , 1992, Nuclear medicine communications.

[27]  F. Buchegger,et al.  The effect of antigen concentration, antibody valency and size, and tumor architecture on antibody binding in multicell spheroids. , 1991, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[28]  C. Meares,et al.  Simplified method for conjugating macrocyclic bifunctional chelating agents to antibodies via 2-iminothiolane. , 1990, Bioconjugate chemistry.

[29]  E. W. Bradley,et al.  Radiobiological comparison of external beam irradiation and radioimmunotherapy in renal cell carcinoma xenografts. , 1989, International journal of radiation oncology, biology, physics.

[30]  S. Denardo,et al.  Development of monoclonal antibody imaging of metastatic prostatic carcinoma , 1989, The Prostate.

[31]  L. T. Dillman.  Radionuclide decay schemes and nuclear parameters for use in radiation-dose estimation. , 1969, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.