Dosimetry-based therapy in metastatic breast cancer patients using Y-90 monoclonal antibody 170H.82 with autologous stem cell support and cyclosporina

Radioimmunoconjugates of 170H.82 (m170), a panadenocarcinoma monoclonal ant ibody, are effective for imaging primary and metastatic breast cancer. To e valuate m170 as a targeting agent for therapy, we developed In-111- and Y-9 0-2-iminothiolane-2-[p-(bromoacetamido)benzyl]-1,4,7,10 tetraazacyclododeca ne-N,N',N",N"'-tetraacet acid-m170 immunoconjugates with 99% purity by mole cular sieving and immunoreactivity comparable to unmodified antibody. In-11 1-m170 pharmacokinetic studies were performed prior to each therapy to dete rmine the maximum dose of Y-90-m170 that could be administered without exce eding a limit of 800 rad to the liver, lungs, or kidneys or 250 rad to the whole body or bone marrow for each of three cycles of treatment. Peripheral blood stem cells (PBSCs) were harvested and cyclosporin A (5 mg/kg twice d aily) was administered as strategies to ameliorate myelosuppression and pre vent the development of MAMA, respectively. An In-111 imaging/pharmacokinet ic study was performed, and the Y-90 dose was calculated and administered. The liver was the 90Y dose-limiting organ. The mean and range of calculated doses (in rad/mCi) for the five patients evaluated were as follows: whole body, 2.3 (2.1-2.4); liver, 17.8 (12.7-22.2); lung, 6.4 (4.8-7.2); kidney, 6.9 (6.3-11.5); marrow, 3.6 (1.9-4.4); and tumors (n = 25), 71.5 (14.1-141. 5). Of the three patients treated, with doses of 37, 54, and 57 mCi of Y-90 , one had a partial response, one had measurable tumor reduction but less t han a partial response, and one had stable disease for more than 1 month. P BSCs prevented prolonged myelosuppression. The therapeutic responses, coupl ed with an absence, thus far, of significant adverse sequelae, suggest that this dosimetry-based approach combined with PBSCs may lead to effective th erapy when higher 90Y doses are reached.