BACKGROUND: Patients with metastatic clear cell renal cell carcinoma (ccRCC) have a dismal prognosis. Therefore, new and less toxic treatments are needed. OBJECTIVE: We determined the maximum tolerated dose (MTD) and potential therapeutic efficacy of multiple infusions of lutetium 177 ((177)Lu)-girentuximab (cG250) on various dose levels in a phase 1 trial in patients with progressive metastasized ccRCC. DESIGN, SETTING, AND PARTICIPANTS: In this uncontrolled case series in 23 patients with progressive ccRCC metastases, cG250 accumulation was verified by diagnostic indium 111-cG250 imaging. Patients then received a high-activity dose of (177)Lu-cG250. INTERVENTION: Groups of three patients received (177)Lu-cG250, starting at a dose level of 1110 MBq/m(2)(177)Lu-cG250, with dose increments of 370 MBq/m(2) per group. In the absence of persistent toxicity, progressive disease, and accelerated blood clearance, patients were eligible for retreatment after 3 mo with 75% of the previous activity dose. Patients could receive a total of three treatment cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Determination of the MTD was the primary and therapeutic efficacy was the secondary outcome measurement of the study. RESULTS AND LIMITATIONS: The MTD was 2405 MBq/m(2) because higher doses resulted in dose-limiting myelotoxicity. Some patients received second (13 of 23 [56%]) and third (4 of 23 [17%]) treatment cycles. Most patients (17 of 23 [74%]) demonstrated stable disease 3 mo after the first treatment, and one patient showed a partial response that lasted for 9 mo. Mean growth of target tumor lesions was reduced from 40.4% (95% confidence interval [CI], ± 17.0) during the last 3 mo before study entry to 5.5% (95% CI, ± 5.3; p<0.001) at 3 mo after the first treatment cycle. No major nonhematologic side effects were observed. CONCLUSIONS: (177)Lu-cG250 radioimmunotherapy in metastatic ccRCC patients is well tolerated at an activity dose level as high as 2405 MBq/m(2) (MTD). Radioimmunotherapy with (177)Lu-cG250 may stabilize previously progressive metastatic ccRCC.
BACKGROUND:Patients with metastatic clear cell renal cell carcinoma (ccRCC) have a dismal prognosis. Therefore, new and less toxic treatments are needed. OBJECTIVE: We determined the maximum tolerated dose (MTD) and potential therapeutic efficacy of multiple infusions of lutetium 177 ((177)Lu)-girentuximab (cG250) on various dose levels in a phase 1 trial in patients with progressive metastasized ccRCC. DESIGN, SETTING, AND PARTICIPANTS: In this uncontrolled case series in 23 patients with progressive ccRCC metastases, cG250 accumulation was verified by diagnostic indium 111-cG250 imaging. Patients then received a high-activity dose of (177)Lu-cG250. INTERVENTION: Groups of three patients received (177)Lu-cG250, starting at a dose level of 1110 MBq/m(2)(177)Lu-cG250, with dose increments of 370 MBq/m(2) per group. In the absence of persistent toxicity, progressive disease, and accelerated blood clearance, patients were eligible for retreatment after 3 mo with 75% of the previous activity dose. Patients could receive a total of three treatment cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Determination of the MTD was the primary and therapeutic efficacy was the secondary outcome measurement of the study. RESULTS AND LIMITATIONS: The MTD was 2405 MBq/m(2) because higher doses resulted in dose-limiting myelotoxicity. Some patients received second (13 of 23 [56%]) and third (4 of 23 [17%]) treatment cycles. Most patients (17 of 23 [74%]) demonstrated stable disease 3 mo after the first treatment, and one patient showed a partial response that lasted for 9 mo. Mean growth of target tumor lesions was reduced from 40.4% (95% confidence interval [CI], ± 17.0) during the last 3 mo before study entry to 5.5% (95% CI, ± 5.3; p<0.001) at 3 mo after the first treatment cycle. No major nonhematologic side effects were observed. CONCLUSIONS: (177)Lu-cG250 radioimmunotherapy in metastatic ccRCC patients is well tolerated at an activity dose level as high as 2405 MBq/m(2) (MTD). Radioimmunotherapy with (177)Lu-cG250 may stabilize previously progressive metastatic ccRCC.
Authors: Sarah M Cheal; Blesida Punzalan; Michael G Doran; Michael J Evans; Joseph R Osborne; Jason S Lewis; Pat Zanzonico; Steven M Larson Journal: Eur J Nucl Med Mol Imaging Date: 2014-03-07 Impact factor: 9.236
Authors: Emmy D G Fleuren; Yvonne M H Versleijen-Jonkers; Sandra Heskamp; Carla M L van Herpen; Wim J G Oyen; Winette T A van der Graaf; Otto C Boerman Journal: Mol Oncol Date: 2014-03-21 Impact factor: 6.603
Authors: Baris Turkbey; Maria L Lindenberg; Stephen Adler; Karen A Kurdziel; Yolanda L McKinney; Juanita Weaver; Cathy D Vocke; Miriam Anver; Gennady Bratslavsky; Philip Eclarinal; Gideon Kwarteng; Frank I Lin; Nana Yaqub-Ogun; Maria J Merino; W Marston Linehan; Peter L Choyke; Adam R Metwalli Journal: Abdom Radiol (NY) Date: 2016-01