High-dose 90Y Mx-diethylenetriaminepentaacetic acid (DTPA)-BrE-3 and autologous hematopoietic stem cell support (AHSCS) for the treatment of advanced breast cancer: a phase I trial.

This Phase I trial explores the use of high-dose 90Y conjugated to the antibreast cancer monoclonal antibody BrE-3 and autologous hematologic cell support in the treatment of women with stage four breast cancer. Nine women with heavily pretreated disease were enrolled. All of the patients had BrE-3-positive tumors by immunostaining and were treated with increasing doses of 90Y (15 mCi/m2, 3 patients), 20 mCi/M2 (six patients), and a fixed (50 mg) dose of BrE-3. 111In-labeled BrE-3 (5 mCi) was given simultaneously for scanning purposes. The only toxicity noted was hematological. Grade 4 platelet toxicity requiring transfusion support occurred in four patients. Grade 4 WBC toxicity was seen in two patients that resolved in 3-9 days. All hematological nadirs occurred approximately 25 days after treatment. Objective partial responses were noted in 4 of 8 (50%) patients with measurable tumors. Dose escalation is ongoing.

Interrelationship between subpressor effects of vasopressin and other vasoactive hormones in the rat.

Measurements of the vasoactive hormones including norepinephrine, angiotensin II and arginine vasopressin, in patients with essential hypertension generally have revealed plasma levels which are considered to be in a subpressor range. The results of recent in vivo studies from our laboratory, however, suggest that norepinephrine, angiotensin II and vasopressin all increase blood pressure by enhancing calcium movement across plasma membranes of vascular smooth muscle. Thus, subpressor levels of these three hormones may interact to increase peripheral vascular resistance and increase blood pressure. In the present study the effect of a subpressor dose of norepinephrine, angiotensin II or vasopressin to potentiate the blood pressure response to a pressor dose of one of these vasoactive hormones was demonstrated in the conscious rat. Furthermore, the combined subpressor doses of two of these three hormones caused a significant rise in blood pressure, even though each hormone by itself did not alter blood pressure. These results therefore raise the possibility that the combined vascular effects of subpressor levels of these three vasoactive hormones might contribute to some, heretofore, unexplained, states of essential hypertension.