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


METHODS
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.
O'Donnell
R T
RT
Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis Medical Center, Sacramento, California 95816, USA.rtodonnell@ucdavis.edu
DeNardo
S J
SJ
Yuan
A
A
Shen
S
S
Richman
C M
CM
Lara
P N
PN
Griffith
I J
IJ
Goldstein
D S
DS
Kukis
D L
DL
Martinez
G S
GS
Mirick
G R
GR
DeNardo
G L
GL
Meyers
F J
FJ
D000230:Adenocarcinoma / Q000628:therapy; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010146:Pain / Q000188:drug therapy; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000628:therapy*; D016499:Radioimmunotherapy; D011874:Radiometry; D013997:Time Factors; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*
C410508:2IT-BAD-Lym-1 monoclonal antibody; D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D015021:Yttrium Radioisotopes; D017430:Prostate-Specific Antigen