Combination of a polyamine-free oral nutritional supplement (ONS) with docetaxel in castrate-resistant prostate cancer (CRPC) patients (pts): A phase II trial.

Abstract

e15131 Background: Polyamines (PA) are essential for cancer cell growth. Reducing exogenous PA (foods + gut flora) and blocking PA synthesis, reduces tumour growth and potentializes chemotherapy in rodent tumour models. We have developed a PA “free” ONS, which inhibits tumour growth by 40% in pre-clinical models and assessed its tolerance with docetaxel in CRPC pts. Methods: 30 pts, 71 ± 7 years, with metastatic CRPC, median PSA: 95 ng/ml, were assessed for tolerance, quality of life (QOL) (QLQ C-30 questionnaire), W.H.O. performance status (P.S.), pain scores and prostate specific antigen (PSA) response. 90% pts were painful. 75% pts had opiate or morphinic analgesics at day 0 (D0). Median pain score is 5 (0 to 10 scale). The PA free ONS was given as sole diet (6 cans a day) for 14 days then progressively reduced and given with low PA containing foods. Docetaxel administration started on day 21 for 6, 75 mg/m2 injections, every three weeks with prednisone. Nutrialys Medical Nutrition, France, provided the PA free ONS. Results: 27 pts were evaluated for the PA ONS free phase. 18 pts completed the trial at scheduled dates and docetaxel doses. 9 pts did not complete the trial: disease progression (n=4), initial thrombocytemia (n=2), 2 deaths and 1 GI intolerance PA free ONS stage: No specific toxicity. QOL (p=0,04), pain (p=0,03) and anorexia (p=0,01) are improved at day 14. 1 pt had a > 50 % PSA decrease. PA free ONS + docetaxel stage: grade 1 or 2 nausea, vomiting or diarrhoea in < 35 % pts, 12% grade 1 neuropathy, no onycholysis or skin toxicity. Body weight and biological parameters are preserved except for two grade 4 neutropenias. P.S., Q.O.L. and pain scores and anorexia are improved. 55% pts cut their analgesics by ≥ 30% WITH stable or improved pain score. 13 pts (70% pts who completed the trial) had an > 50% PSA decrease with an 8 weeks median response time. Conclusions: A PA free ONS exclusive diet is well tolerated with significant QOL and pain improvements. The docetaxel PA free ONS combination tolerance is excellent with improved P.S., pain score and analgesic reduction. AE during chemotherapy are minimal. PSA responses are observed in a significant proportion of treated patients.