Phase I trial of docetaxel/prednisone plus fractionated dose radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody 177lu-J591 in patients with metastatic, castration-resistant prostate cancer (mCRPC).

Genitourinary (Prostate) Cancer
Session Type and Session Title: 
General Poster Session, Genitourinary (Prostate) Cancer
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 5064)
Scott T. Tagawa, Young E. Whang, Gurveen Kaur, Shankar Vallabhajosula, Paul J. Christos, Anastasia Nikolopoulou, Yuliya Jhanwar, Arif Sheikh, Adam Ireland, Carmen Garcias-Espana, Stanley J. Goldsmith, Himisha Beltran, Neil Harrison Bander, David M. Nanus; Weill Cornell Medical College, New York, NY; The University of North Carolina at Chapel Hill, Chapel Hill, NC

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Abstract Disclosures


Background: Docetaxel remains a standard agent for mCRPC and has radiosensitizing properties. 177Lu-J591 delivered with fractionated dosing leads to less myelosuppression while maintaining efficacy in mCRPC. This study was designed to determine the safety, dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of fractionated 177Lu-J591 administered concurrently with standard docetaxel. Methods: Men with progressivemCRPC received docetaxel 75 mg/m2 every 3 weeks with escalating 2 fractionated doses of 177Lu-J591 (initial dose 20 mCi/m2 x2 up to max of 40 mCi/m2 x2) with cycle 3. Cycle 4 of docetaxel was planned 6 weeks after cycle 3 to allow for recovery from 177Lu-J591-associated hematologic toxicity. DLT was defined as delay in docetaxel >3 weeks, prolonged myelosuppression or need for >2 platelet (plt) transfusions, febrile neutropenia, or grade >2 non-heme toxicity following 177Lu-J591. PSA was assessed prior to each cycle and CTC count (CellSearch) was assessed at baseline and after 177Lu-J591. Results: 15 men with median age 67.3 (range 49.2-80.8), PSA 84.3 (17-776), 73.3% with elevated LDH, 71.4% unfavorable CTC counts received up to the highest anticipated dose (40 mCi/m2 x2). No DLT was seen at any dose level. Significant toxicity was limited to reversible myelosuppression. Gr 4 neutropenia without fever occurred in 3 (20%) and Gr 4 plts in 2 (13.3%), with 2 receiving prophylactic plt transfusion. No Gr >2 non-heme toxicity was observed. 13 had PSA decline, with 11 (73.3%) and 12 (80%) having >50% and >30% PSA decline respectively. All 14 evaluable men had decline (85.7%) or persistently undetectable (14.3%) CTC counts, with 78.6% having CTC counts decline by >50% and 78.6% having favorable counts after 177Lu-J591. Of 10 analyzed to date, all had targeting of known sites of disease by planar 177Lu-J591 imaging. Conclusions: The combination offractionated dose 177Lu-J591 and docetaxel/prednisone is well tolerated in patients with mCRPC. Without pre-selection, accurate targeting of known sites of disease and a strong preliminary efficacy signal was observed. Clinical trial information: NCT00916123.