Jaspreet S Batra1, Muhammad Junaid Niaz1, Young E Whang2, Arif Sheikh3, Charlene Thomas4, Paul Christos4, Shankar Vallabhajosula5, Yuliya S Jhanwar5, Ana M Molina6, David M Nanus7, Joseph R Osborne8, Neil H Bander9, Scott T Tagawa10. 1. Department of Urology, Weill Cornell Medicine, New York, NY. 2. Department of Medicine, Division of Hematology/Oncology, University of North Carolina School of Medicine, Chapel Hill, NC. 3. Department of Radiology, Icahn School of Medciine at Mount Sinai, New York, NY. 4. Department of Biostatistics and Epidemiology, Weill Cornell Medicine, New York, NY. 5. Division of Molecular Imaging and Therapeutics, Department of Radiology, Weill Cornell Medicine, New York, NY. 6. Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY; Meyer Cancer Center, Weill Cornell Medicine, NewYork Presbyterian Hospital, New York, NY. 7. Department of Urology, Weill Cornell Medicine, New York, NY; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY; Meyer Cancer Center, Weill Cornell Medicine, NewYork Presbyterian Hospital, New York, NY. 8. Division of Molecular Imaging and Therapeutics, Department of Radiology, Weill Cornell Medicine, New York, NY; Meyer Cancer Center, Weill Cornell Medicine, NewYork Presbyterian Hospital, New York, NY. 9. Department of Urology, Weill Cornell Medicine, New York, NY; Meyer Cancer Center, Weill Cornell Medicine, NewYork Presbyterian Hospital, New York, NY. 10. Department of Urology, Weill Cornell Medicine, New York, NY; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY; Meyer Cancer Center, Weill Cornell Medicine, NewYork Presbyterian Hospital, New York, NY. Electronic address: stt2007@med.cornell.edu.
Abstract
BACKGROUND: Docetaxel remains a standard of care for metatsatic castration resistant porstate cancer (mCRPC) and has radiosensitizing properties. The dose limiting toxicity (DLT) of radioimmunotherapy is myelosuppression; dose fractionation of 177Lu-J591 allows similar administered doses with less toxicity. This study (NCT00916123) was designed to determine the safety, DLT, and maximum tolerated dose of fractionated 177Lu-J591 administered concurrently with standard docetaxel. METHODS: Men with progressive mCRPC received docetaxel 75 mg/m2 every 3 weeks with escalating 2 fractionated doses of 177Lu-J591 (1.48 GBq/m2 up to max of 2.96 GBq/m2) 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 transfusions, febrile neutropenia, or grade ≥3 nonhematological toxicity following 177Lu-J591. PSA was assessed prior to each cycle and serial computed tomography (CT) and bone scan were performed. RESULTS: Fifteen men with progressive mCRPC received dose-escalated targeted radionuclide therapy in 4 cohorts up to the highest planned dose (2.96 GBq/m2). No DLT was seen at any dose level. Grade 4 neutropenia without fever occurred in 8 (53.5%) and thromboytopenia in 2 (13.3%), with 2 receiving prophylactic platelet transfusion. No grade ≥3 nonhematological toxicity was observed. 11 (73.3%) had >50% PSA decline, with 78.6% having favorable circulating tumor cell counts after 177Lu-J591. All patients had targeting of known sites of disease by planar 177Lu-J591 imaging. CONCLUSION: The combination of 177Lu-J591 delivered as a single fractionated cycle with docetaxel/prednisone is feasible in patients with mCRPC. Without preselection for prostate-specific membrane antigen, accurate targeting of known sites of disease and a strong preliminary efficacy signal was observed.
BACKGROUND:Docetaxel remains a standard of care for metatsatic castration resistant porstate cancer (mCRPC) and has radiosensitizing properties. The dose limiting toxicity (DLT) of radioimmunotherapy is myelosuppression; dose fractionation of 177Lu-J591 allows similar administered doses with less toxicity. This study (NCT00916123) was designed to determine the safety, DLT, and maximum tolerated dose of fractionated 177Lu-J591 administered concurrently with standard docetaxel. METHODS:Men with progressive mCRPC received docetaxel 75 mg/m2 every 3 weeks with escalating 2 fractionated doses of 177Lu-J591 (1.48 GBq/m2 up to max of 2.96 GBq/m2) 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 transfusions, febrile neutropenia, or grade ≥3 nonhematological toxicity following 177Lu-J591. PSA was assessed prior to each cycle and serial computed tomography (CT) and bone scan were performed. RESULTS: Fifteen men with progressive mCRPC received dose-escalated targeted radionuclide therapy in 4 cohorts up to the highest planned dose (2.96 GBq/m2). No DLT was seen at any dose level. Grade 4 neutropenia without fever occurred in 8 (53.5%) and thromboytopenia in 2 (13.3%), with 2 receiving prophylactic platelet transfusion. No grade ≥3 nonhematological toxicity was observed. 11 (73.3%) had >50% PSA decline, with 78.6% having favorable circulating tumor cell counts after 177Lu-J591. All patients had targeting of known sites of disease by planar 177Lu-J591 imaging. CONCLUSION: The combination of 177Lu-J591 delivered as a single fractionated cycle with docetaxel/prednisone is feasible in patients with mCRPC. Without preselection for prostate-specific membrane antigen, accurate targeting of known sites of disease and a strong preliminary efficacy signal was observed.
Authors: Panagiotis J Vlachostergios; Muhammad Junaid Niaz; Michael Sun; Seyed Ali Mosallaie; Charlene Thomas; Paul J Christos; Joseph R Osborne; Ana M Molina; David M Nanus; Neil H Bander; Scott T Tagawa Journal: Front Oncol Date: 2021-02-18 Impact factor: 6.244
Authors: M K Ramirez-Fort; B Meier-Schiesser; K Lachance; S S Mahase; C D Church; M J Niaz; H Liu; V Navarro; A Nikolopoulou; D V Kazakov; E Contassot; D P Nguyen; J Sach; L Hadravsky; Y Sheng; S T Tagawa; X Wu; C S Lange; L E French; P T Nghiem; N H Bander Journal: Skin Health Dis Date: 2020-11-28