PMID- 32924093
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20220907
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 39
IP  - 2
DP  - 2021 Apr
TI  - Phase II trial of SM-88, a cancer metabolism based therapy, in non-metastatic 
      biochemical recurrent prostate cancer.
PG  - 499-508
LID - 10.1007/s10637-020-00993-4 [doi]
AB  - Background Androgen deprivation therapy (ADT) is a standard treatment for 
      high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is 
      not curative and associated with toxicity. Racemetyrosine (SM-88) is an 
      amino-acid analogue used with methoxsalen, phenytoin, and sirolimus (MPS) to 
      enhance SM-88 activity. Method A phase 1b/2, open-label trial in BRPC and rising 
      PSA. Patients were given daily SM-88 (230 mg BID), methoxsalen (10 mg), phenytoin 
      (50 mg), and sirolimus (0.5 mg)). Outcome measures included changes in PSA, 
      circulating tumor cells (CTCs) and imaging. Results 34 subjects were screened, 23 
      treated and 21 remained on study for >/=12 weeks. The median PSA was 6.4 ng/ml 
      (range 1.7-80.1); doubling-time 6.2 months (range 1.4-36.6) and baseline 
      testosterone 319.1 ng/ml (range 2.5-913.7). Median duration of therapy was 
      6.5 months (2.6-14.0). CTCs (median 48.5 cells/4 ml (range 15-268) at baseline) 
      decreased a median of 65.3% in 18 of 19 patients. For patients who achieved an 
      absolute CTC nadir count of <10 cells/4 ml (n = 10), disease control was 100% 
      i.e. no metastases or PSA progression, while on trial (p = 0.005). PSA fell by 
      >/=50% in 4.3% (1 subject). No patients developed metastatic disease while on 
      treatment (metastases free survival =100%). There were no treatment-related 
      adverse events (AEs) and quality of life was unchanged from baseline on the EORTC 
      QLQ-C30 and QLQ-PR25. Testosterone levels rose slightly on SM-88 and were 
      unrelated to efficacy or toxicity. Conclusions Use of SM-88 was associated with 
      disease control while maintaining QOL. SM-88 may delay the need for ADT and the 
      associated hormonal side effects. Larger trials are planned.Trial registration 
      number, date of registration - NCT02796898, June 13, 2016.
FAU - Gartrell, Benjamin A
AU  - Gartrell BA
AD  - Albert Einstein College of Medicine, Departments of Oncology and Urology, 
      Montefiore Einstein Center for Cancer Care, Montefiore Medical Center, New York, 
      NY, USA. BGartrel@Montefiore.org.
FAU - Roach, Mack 3rd
AU  - Roach M 3rd
AD  - Departments of Radiation Oncology & Urology, University of California San 
      Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center (HDFCC), San 
      Francisco, CA, USA.
FAU - Retter, Avi
AU  - Retter A
AD  - NY Cancer and Blood Specialist, East Setauket, NY, USA.
FAU - Sokol, Gerald H
AU  - Sokol GH
AD  - Division of Clinical Pharmacology, Uniform Services University of the Health 
      Sciences, Bethesda, MD, USA.
AD  - Florida Cancer Specialist and Research Institute, Fort Myers, FL, USA.
AD  - TYME Inc, New York, NY, USA.
FAU - Del Priore, Giuseppe
AU  - Del Priore G
AD  - TYME Inc, New York, NY, USA.
FAU - Scher, Howard I
AU  - Scher HI
AD  - Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering 
      Cancer Center, New York, NY, USA.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02796898
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200913
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Androgen Antagonists)
RN  - 0 (racemetyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 6158TKW0C5 (Phenytoin)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
RN  - U4VJ29L7BQ (Methoxsalen)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Androgen Antagonists/administration & dosage/adverse effects/*therapeutic use
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Methoxsalen/administration & dosage
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local
MH  - Phenytoin/administration & dosage
MH  - Prostate-Specific Antigen
MH  - Prostatic Neoplasms/*drug therapy/pathology
MH  - Quality of Life
MH  - Sirolimus/administration & dosage
MH  - Tyrosine/administration & dosage/adverse effects/*analogs & 
      derivatives/therapeutic use
PMC - PMC7960617
OTO - NOTNLM
OT  - Metabolism based therapy
OT  - Prostate Cancer
OT  - SM-88
COIS- NY Cancer and Blood received research support from TYME. GHS and GDP are 
      employees or board members at TYME and received salary, equity and other support.
EDAT- 2020/09/15 06:00
MHDA- 2022/02/03 06:00
PMCR- 2020/09/13
CRDT- 2020/09/14 05:58
PHST- 2020/07/28 00:00 [received]
PHST- 2020/08/21 00:00 [accepted]
PHST- 2020/09/15 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2020/09/14 05:58 [entrez]
PHST- 2020/09/13 00:00 [pmc-release]
AID - 10.1007/s10637-020-00993-4 [pii]
AID - 993 [pii]
AID - 10.1007/s10637-020-00993-4 [doi]
PST - ppublish
SO  - Invest New Drugs. 2021 Apr;39(2):499-508. doi: 10.1007/s10637-020-00993-4. Epub 
      2020 Sep 13.