Phase II trial of SM-88, a cancer metabolism based therapy, in non-metastatic biochemical recurrent prostate cancer

• Published in: Investigational new drugs Vol. 39; no. 2; pp. 499 - 508
• Main Authors: Gartrell, Benjamin A., Roach, Mack, Retter, Avi, Sokol, Gerald H., Del Priore, Giuseppe, Scher, Howard I.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2021; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Amino acids; Androgen Antagonists - administration & dosage; Androgen Antagonists - adverse effects; Androgen Antagonists - therapeutic use; Clinical trials; Deprivation; Disease control; Health risks; Humans; Kaplan-Meier Estimate; Male; Medical treatment; Medicine; Medicine & Public Health; Metabolism; Metastases; Metastasis; Methoxsalen; Methoxsalen - administration & dosage; Middle Aged; Neoplasm Recurrence, Local; Oncology; Pharmacology/Toxicology; Phase II Studies; Phenytoin; Phenytoin - administration & dosage; Prostate cancer; Prostate-Specific Antigen; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Quality of Life; Rapamycin; Side effects; Sirolimus - administration & dosage; Testosterone; Therapy; Toxicity; Tumor cells; Metabolism based therapy; SM-88; Prostate Cancer
• ISSN: 0167-6997; 1573-0646; 1573-0646
• DOI: 10.1007/s10637-020-00993-4

Summary 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