Typical hormone deprivation side effects compared to SM-88 therapy for rising PSA.

Abstract

79 Background: Treatment for rising PSA non-metastatic prostate cancer (nmPC) includes multifaceted hormone therapies (HT) associated with increasing related toxicity; in aggregate the risk benefit ratio is not ideal. We report on the use before HT, of SM-88, a novel combination therapy (amino acid analogue, CYP3A4 inducer, mTOR inhibitor and catalyst) based on the Warburg effect without known hormone related toxicity. Methods: Prospective ongoing Phase II of SM-88 (230 mg po bid) in recurrent nmPC with rising PSA (PCWG3 definition), no radiographically identified metastases at baseline and detectable CTCs. Results: From Sept 2016 to Dec 2017, there have been 31 consented (34 planned) with 23 evaluable (completed > 1 cycle). Mean age 68.9; BMI 28.7; 38% black and 62% post RT. Mean testosterone (T) rose from 319 to 382 ng/dl (p=.19). Typical HT related side-effects were not observed: 96% of subjects reported no hot flashes, 91% no gynecomastia, 83% interest and 61% activity in sex, 78% excellent or nearly so overall health and 74% excellent QOL on at least 50% of their EORTC questionnaires; weight (-0.2 kg), hct (0%), glu (+2 mg/dl), urinary N telopeptide (-4.2 nmol), MAP (normotensives -2 mmHg, hypertensives -3 mmHg), heart rate (-2.4 beats/min), QTc (-3 ms) with no newly emergent >480 ms, serum Ca++ (-0.006 mg/dL), LDH (+6.4 u/L), bsAlkPhos (+6.2 u/L), triglycerides (-5.2 mg/dL), total protein (0.05 g/dL) and albumin (0.02 g/dL). Neutrophil lymphocyte ratio decreased at the end of cycle 1 in 100% (n=5, median 2.4) of those who progressed to subsequent therapy vs 47% of those who did not (p=.05). AEs occurred in 16 subjects: 1 unrelated Grade (G) 3; 0 G 4; 14/26 G 1-2 possibly related to drug. No AEs were related to T levels. From initial diagnosis of PSA rise (median 9, 3-18 months), 96% (22/23) have remained metastases free and 78% (18/23) remained free of additional HT (p<.05). There were no skeletal or cardiovascular events. Conclusions: SM-88 may be useful in delaying the start of HT. While on SM88 subjects did not report any T or therapy related AEs >G2. SM88 may be useful in prostate cancer patients who are more sensitive or vulnerable to HT related toxicity while maintaining stable PSA values. Prospective trials are planned to confirm its utility. Clinical trial information: NCT02796898.