Receptor-mediated radiotherapy with Y-90-DOTA-D-Phe(1)-Tyr(3)-octreotide

A newly developed somatostatin radioligand, DOTA-[D-Phe(1)-Tyr(3)]-octreoti de (DOTATOC), has been synthesised for therapeutic purposes, because of its stable and easy labelling with yttrium-90. The aim of this study was to de termine the dosage, safety profile and therapeutic efficacy of Y-90-DOTATOC in patients with cancers expressing somatostatin receptors. We recruited 3 0 patients with histologically confirmed cancer. The main inclusion criteri on was the presence of somatostatin receptors as documented by In-111-DOTAT OC scintigraphy, 90Y-DOTATOC was injected intravenously using a horizontal protocol: patients received equivalent-activity doses in each of three cycl es over 6 months. The first six patients received 1.11 GBq per cycle and th e four successive groups of six patients received doses increasing in 0.37- GBq steps. Toxicity was evaluated according to WHO criteria. No patient had acute or delayed adverse reactions up to 2.59 GBq Y-90-DOTATOC per cycle ( total 7.77 GBq). After a total dose of 3.33 GBq, one patient developed grad e II renal toxicity 6 months later. The maximum tolerated dose per cycle ha s not yet been reached, although transient lymphocytopenia has been observe d. Total injectable activity is limited by the fact that the maximum dose t olerated by the kidneys has been estimated at 20-25 Gy. Complete or partial tumour mass reduction occurred in 23% of patients; 64% had stable and 13% progressive disease. It is concluded that high activities of Y-90-DOTATOC c an be administered with a low risk of myelotoxicity, although the cumulativ e radiation dose to the kidneys is a limiting factor and requires careful e valuation, Objective therapeutic responses have been observed.