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 language | English (US) |
|---|---|
| Pages (from-to) | 1561-1568 |
| Number of pages | 8 |
| Journal | Clinical Cancer Research |
| Volume | 7 |
| Issue number | 6 |
| State | Published - 2001 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=0034895678&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034895678&partnerID=8YFLogxK
M3 - Article
C2 - 11410491
AN - SCOPUS:0034895678
VL - 7
SP - 1561
EP - 1568
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 6
ER -