Treatment of hormone-refractory prostate cancer with 90Y-CYT-356 monoclonal antibody.
A Phase I dose-escalation study using 90Y-CYT-356 monoclonal antibody was performed in 12 patients with hormone-refractory prostate carcinoma. Biodistribution studies using 111In-CYT-356 were performed 1 week before 90Y-CYT-356 administration. Of the 12 patients, 58% had at least one site of disease imaged after administration of 111In-CYT-356. The dose of 90Y ranged from 1.83-12 mCi/m2. Both 111In and 90Y-CYT-356 were tolerated well, without significant nonhematological toxicity. Myelosuppression was the dose-limiting toxicity and occurred at dose levels of 4.5-12 mCi/m2. Of the patients receiving </=9 mCi/m2, 55% had grade 1 or 2 leukopenia and/or thrombocytopenia. Two of three patients treated with 12 mCi/m2 experienced grade 3 thrombocytopenia and leukopenia. One patient treated with 12 mCi/m2 had grade 4 neutropenia. The maximum tolerated dose of 90Y-CYT-356 was 9 mCi/m2. Only one patient developed a human anti-mouse antibody 4 weeks after treatment. No patient attained a complete or partial response based on prostate-specific antigen and/or radiological criteria. Three patients had transient subjective improvement in the symptomatology of their disease. In addition, patients treated with 12 mCi/m2 of 90Y-CYT-356 had a slightly longer freedom from disease progression than patients treated with doses of 90Y-CYT-356 </=9 mCi/m2.
Deb
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Department of Radiation Oncology, St. Luke's Hospital, Bethlehem, Pennsylvania 18015, USA.
Goris
M
M
Trisler
K
K
Fowler
S
S
Saal
J
J
Ning
S
S
Becker
M
M
Marquez
C
C
Knox
S
S
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; C101315:Capromab Pendetide