Phase II Study of Low-Dose Abiraterone With Food.

[pjoshea13]

New study below [1].

BBruce has already referenced the study, but not the abstract. Some significance was given to the fact that the food was low-fat.

Here is my response to the earlier post:

"It's easy to miss the point. It isn't so much about the fat as the meal.

"We sought to test the hypothesis that low-dose AA (LOW; 250 mg with a low-fat meal) would have comparable activity to standard AA (STD; 1,000 mg fasting) in patients with CRPC."

"At 12 weeks, there was a greater effect on PSA in the LOW arm ... compared with STD (-1.19), and noninferiority of LOW was established according to predefined criteria." [1]

NOTE that there was no "HIGH" arm, so we can draw no conclusion about a cheese burger breakfast.

Noninferiority was established, so men can have the drug with food, & at quarter of the dose with the low-fat breakfast. We don't know what the dose would be with a high fat meal.

As with many food-related studies, there seems to be bias against fat. The researchers probably felt that high fat was bad. & traditional breakfasts can be high in fat. Hence we have the structure of the study & the inevitable misinterpretation of the findings.

Note that "a conventional low-fat breakfast" was not defined [2]. But they don't mean Dean Ornish."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/295...

J Clin Oncol. 2018 Mar 28:JCO2017764381. doi: 10.1200/JCO.2017.76.4381. [Epub ahead of print]

Prospective International Randomized Phase II Study of Low-Dose Abiraterone With Food Versus Standard Dose Abiraterone In Castration-Resistant Prostate Cancer.

Szmulewitz RZ1, Peer CJ1, Ibraheem A1, Martinez E1, Kozloff MF1, Carthon B1, Harvey RD1, Fishkin P1, Yong WP1, Chiong E1, Nabhan C1, Karrison T1, Figg WD1, Stadler WM1, Ratain MJ1.

Author information

Abstract

Purpose Abiraterone acetate (AA) is a standard of care for metastatic castration-resistant prostate cancer (CRPC). Despite a large food effect, AA was administered under fasting conditions in its pivotal trials. We sought to test the hypothesis that low-dose AA (LOW; 250 mg with a low-fat meal) would have comparable activity to standard AA (STD; 1,000 mg fasting) in patients with CRPC. Patients and Methods Patients (n = 72) with progressive CRPC from seven institutions in the United States and Singapore were randomly assigned to STD or LOW. Both arms received prednisone 5 mg twice daily. Prostate-specific antigen (PSA) was assessed monthly, and testosterone/dehydroepiandrosterone sulfate were assessed every 12 weeks with disease burden radiographic assessments. Plasma was collected for drug concentrations. Log change in PSA, as a pharmacodynamic biomarker for efficacy, was the primary end point, using a noninferiority design. Progression-free survival (PFS), PSA response (≥ 50% reduction), change in androgen levels, and pharmacokinetics were secondary end points. Results Thirty-six patients were accrued to both arms. At 12 weeks, there was a greater effect on PSA in the LOW arm (mean log change, -1.59) compared with STD (-1.19), and noninferiority of LOW was established according to predefined criteria. The PSA response rate was 58% in LOW and 50% in STD, and the median PFS was approximately 9 months in both groups. Androgen levels decreased similarly in both arms. Although there was no difference in PSA response or PFS, abiraterone concentrations were higher in STD. Conclusion Low-dose AA (with low-fat breakfast) is noninferior to standard dosing with respect to PSA metrics. Given the pharmacoeconomic implications, these data warrant consideration by prescribers, payers, and patients. Additional studies are indicated to assess the long-term efficacy of this approach.

PMID: 29590007 DOI: 10.1200/JCO.2017.76.4381

...

[2] clinicaltrials.gov/ct2/show...

[Dan59]

Thank You Patrick. When I did zytiga with food, I did the full dose with a high fat meal, talking bacon ,eggs and homefries with high fat yogurt,and was doing xtandi at same time. Liver functions stayed normal, got an extra 5 months by doing this. I had been on zytiga first for 1.5 years, after being heavily pretreated with ketoconazole, then added xtandi, 2 years or more later I started eating high fat and doing xtandi at night got 5 more months before starting chemo, so this was 4 years after originally starting zytiga. My Harvard Oncologist said “Often we find when zytiga stops responding we find it is no longer being absorbed and we find that food increases absorption”. I agree with guys with a financial concern this study shows you can get a better response by doing 1 zytiga with a low fat meal, as opposed to full dose fasting. Sitting in the house of drips today as I type, getting my 3rd Jevtana, psa was down 20 to 123 after first 2, so it looks like it is working.

Dan

[j-o-h-n in reply to Dan59]

Good for you... "keep it up".... (oops we no longer can say that).

Good Luck and Good Health.

j-o-h-n Friday 03/30/2018 1:30 PM EDT