Abiraterone & Food

[pjoshea13]

New Dutch study below [1].

One Abi dose size fits all - actually doesn't.

"At the currently used fixed dose of 1000 mg once daily in modified fasting state, 40% of patients do not reach the efficacy threshold of a minimum plasma concentration (Cmin) ≥ 8.4 ng/mL and are thereby at risk of decreased treatment efficacy."

"In total, 32 evaluable patients were included, of which 20 patients (63%) had a Cmin < 8.4 ng/mL at a certain time point during treatment. These patients were recommended to take abiraterone acetate concomitantly with food, after which Cmin increased from 6.9 ng/mL to 27 ng/mL (p < 0.001) without additional toxicities. This intervention led to adequate exposure in 28 patients (87.5%)."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/321...

Eur J Cancer

, 130, 32-38 2020 Mar 12[Online ahead of print]

Concomitant Intake of Abiraterone Acetate and Food to Increase Pharmacokinetic Exposure: Real Life Data From a Therapeutic Drug Monitoring Programme

Stefanie L Groenland 1 , Merel van Nuland 2 , Andries M Bergman 3 , Jeantine M de Feijter 3 , Vincent O Dezentje 3 , Hilde Rosing 2 , Jos H Beijnen 4 , Alwin D R Huitema 5 , Neeltje Steeghs 6 , Dutch Pharmacology Oncology Group (DPOG)

Affiliations collapse

Affiliations

1 Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands. Electronic address: [e-mail].

2 Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, the Netherlands.

3 Division of Medical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, the Netherlands.

4 Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, the Netherlands; Department of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.

5 Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, the Netherlands; Department of Clinical Pharmacy, University Medical Center, Utrecht University, Utrecht, the Netherlalnds.

6 Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.

PMID: 32172196 DOI: 10.1016/j.ejca.2020.02.012

Abstract

Aim: Abiraterone acetate is approved for the treatment of metastatic prostate cancer. At the currently used fixed dose of 1000 mg once daily in modified fasting state, 40% of patients do not reach the efficacy threshold of a minimum plasma concentration (Cmin) ≥ 8.4 ng/mL and are thereby at risk of decreased treatment efficacy. This study aims to evaluate whether pharmacokinetically (PK) guided abiraterone acetate dosing with a food intervention is feasible and results in an increased percentage of patients with concentrations above the target.

Methods: Patients starting regular treatment with abiraterone acetate in modified fasting state were included. Pharmacokinetic analysis was performed 4, 8 and 12 weeks after start of treatment and every 12 weeks thereafter. In case of Cmin < 8.4 ng/mL and acceptable toxicity, a PK-guided intervention was recommended. The first step was concomitant intake of abiraterone acetate with a light meal or a snack.

Results: In total, 32 evaluable patients were included, of which 20 patients (63%) had a Cmin < 8.4 ng/mL at a certain time point during treatment. These patients were recommended to take abiraterone acetate concomitantly with food, after which Cmin increased from 6.9 ng/mL to 27 ng/mL (p < 0.001) without additional toxicities. This intervention led to adequate exposure in 28 patients (87.5%).

Conclusion: Therapeutic drug monitoring of abiraterone was applied in clinical practice and proved to be feasible. Concomitant intake with food resulted in a significant increase in Cmin and offers a cost-neutral opportunity to optimise exposure in patients with low Cmin.

Keywords: abiraterone acetate; drug monitoring; pharmacokinetics; prostate cancer.

Copyright © 2020 Elsevier Ltd. All rights reserved.

[cesces]

That's sort of troubling.

[keepinon]

So they were taking the full dose of 1000 mg with food?

[Hidden]

Good info. During approval the manufacturer had people take it on an empty stomach. No real reason for them to redo the approval for it to be taken with food (obviously no profit incentive since it would result in less drug sales).

I've taken mine with/without food. I think I'll go to half dose with food (500mg/day). Note that my primary SOC oncologist has told me many times that we don't really know if 500mg provides decent effects with less side effects and cost - so she's told me that I can take 1000mg or 750mg or 500mg. My choice (I like her).

[Mikeski in reply to Hidden]

Agree, that’s interesting. I’m too gullible, I always try to be a good patient and do as directed, assuming they have our best interests (our lives!) in mind and not their bottom line.

[Hidden]

Do you know if we could measure serum levels? Be great to verify w/wo food and dosing.

[depotdoug]

My MO stays. With me @ 250mg for the next 90 days. He specifically asked me are you taking you Abiraterone with food? Yes low fat breakfast food. Just like the DR ordered. That may change anytime. Like the COVID -19 responses are .

Not sure if I’m making any sense But not getting icy sleep either with my Prednisone high. Doing what my MO tells me.

[immunity1]

Useful article thanks. R

[Grumpyswife]

My husband tried taking 250 with food and his PSA went up. Now it's not really working at full dose anyway as his PSA rose this month. It maybe a good time to experiment with full dose with a bit of food.

Thanks for article.

[Hirsch]

Anyone know what a modified fasting state is?

[pjoshea13 in reply to Hirsch]

I believe they are referring to current instructions:

'Zytiga should be taken on an empty stomach, either one 1 before or 2 hours after a meal.'

i.e. take on an empty stomach

-Patrick

[Hirsch in reply to pjoshea13]

Thanks Patrick