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Phase I trial of docetaxel plus lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (Lu-J591) for metastatic castration-resistant prostate cancer.

TitlePhase I trial of docetaxel plus lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (Lu-J591) for metastatic castration-resistant prostate cancer.
Publication TypeJournal Article
Year of Publication2020
AuthorsBatra JS, Niaz MJunaid, Whang YE, Sheikh A, Thomas C, Christos P, Vallabhajosula S, Jhanwar YS, Molina AM, Nanus DM, Osborne JR, Bander NH, Tagawa ST
JournalUrol Oncol
Date Published2020 Jun 27
ISSN1873-2496
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 Lu-J591 allows similar administered doses with less toxicity. This study (NCT00916123) was designed to determine the safety, DLT, and maximum tolerated dose of fractionated Lu-J591 administered concurrently with standard docetaxel.

METHODS: Men with progressive mCRPC received docetaxel 75 mg/m every 3 weeks with escalating 2 fractionated doses of Lu-J591 (1.48 GBq/m up to max of 2.96 GBq/m) with cycle 3. Cycle 4 of docetaxel was planned 6 weeks after cycle 3 to allow for recovery from Lu-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 Lu-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/m). 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 Lu-J591. All patients had targeting of known sites of disease by planar Lu-J591 imaging.

CONCLUSION: The combination of Lu-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.

DOI10.1016/j.urolonc.2020.05.028
Alternate JournalUrol. Oncol.
PubMed ID32600929
Division: 
Biostatistics
Category: 
Faculty Publication