Authors:
A.B. Stillebroer, O.C. Boerman, W.J. Oyen, P.F. Mulders, E. Oosterwijk, I.M. Desar, & C.M. van Herpen
Summary:
Objectives - Monoclonal antibody cG250 recognizes carbonic anhydrase IX, an antigen abundantly expressed in Renal Cell Carcinoma (RCC). Here, we determined the MTD and preliminary therapeutic efficacy of multiple infusions of Lu-177-cG250 in patients with progressive RCC.
Methods - Patients with progressive metastatic RCC were eligible. After cG250 targeting was verified by In-111-cG250 imaging, patients received high dose Lu-177-cG250. Three patients were treated per dose level (initial dose level 1110 MBq/m2, dose increments 370 MBq/m2 until the maximum tolerated dose (MTD)). Patients were evaluated for toxicity during treatment and therapeutic efficacy was evaluated with CT-scan. When progressive disease and accelerated blood clearance were absent after 3 months, patients were eligible for re-treatment with 75% of the previous dose. In total patients could receive a maximum of 3 doses.
Results - The MTD was determined at 2405 MBq/m2, since higher doses resulted in dose-limiting myelotoxicity. In-111-cG250 and Lu-177-cG250 showed excellent targeting of tumor lesions in all patients. In-111-cG250 images could be used to predict Lu-177-cG250 radiation doses to normal tissues and tumors. Patients received 2nd (10/20) and 3rd (3/20) treatment cycles. Most patients (14/20) demonstrated stable disease 12 weeks after treatment and one patient showed a partial response for 9 months. Average growth of all tumor lesions was reduced from 28.5% increase in size according to RECIST (95%CI 12.5) during the 3 months before treatment to 4.1% (95%CI 6.2, p=0.002) during the 3 months after the 1st treatment cycle.
Conclusions - Lu-177-cG250 showed excellent targeting of RCC lesions. MTD of RIT with Lu-177-cG250 was 2405 MBq/m2. Lu-177-cG250 treatment could stabilize previously progressive metastatic RCC.
Source:
Society of Nuclear Medicine 58th Annual Meeting; Scientific Paper 359, San Antonio, Texas (06/04-08/11)