# Phase 1 trial of abiraterone acetate confirms that castration-resistant prostate cancer commonly remains hormone driven

Source: https://onco.cc/key-papers/paper-attard-abiraterone-phase-1-cyp17-jco-2008/  
OnCo record `paper-attard-abiraterone-phase-1-cyp17-jco-2008` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Twenty-one men whose prostate cancer had already stopped responding to every hormone treatment available were given a drug that shuts off the last remaining source of androgen. Two thirds had their PSA fall, which proved the cancer had never stopped depending on the hormone.

## Summary

Gerhardt Attard, Johann de Bono and colleagues at the Royal Marsden and the Institute of Cancer Research ran the first-in-human study of abiraterone acetate, a selective inhibitor of cytochrome P450 17A1 (CYP17), the enzyme that makes androgen in the adrenal gland and in the tumour itself. Twenty-one chemotherapy-naive men whose disease was resistant to multiple hormonal therapies were dosed through five levels from 250 mg to 2,000 mg.

The result settled a twenty-year argument about what castration-resistant prostate cancer is. If the disease were genuinely hormone-refractory, removing the residual androgen would do nothing. It did a great deal, and the secondary mineralocorticoid excess that the drug produces (hypertension, hypokalaemia, lower-limb oedema) was managed with a mineralocorticoid receptor antagonist, which is why abiraterone is still given with a steroid today.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Also known as: Attard 2008 abiraterone phase 1; CYP17 inhibition abiraterone first-in-human
- Tags: prostate-evidence
- Journal: Journal of Clinical Oncology
- Year: 2008
- DOI: 10.1200/jco.2007.15.9749
- Authors: Attard G, Reid AH, Yap TA, et al.
- Findings: Declines in prostate-specific antigen of at least 30 percent in 14 of 21 patients (66 percent), at least 50 percent in 12 (57 percent) and at least 90 percent in 6 (29 percent).; Responses lasted between 69 and at least 578 days.; 1,000 mg was selected for cohort expansion (9 further patients) because of a plateau in pharmacodynamic effect above that dose.; Administration suppressed serum testosterone, downstream androgenic steroids and estradiol in all patients, and raised adrenocorticotropic hormone and the steroids upstream of CYP17.; The anticipated toxicities of secondary mineralocorticoid excess (hypertension, hypokalaemia and lower-limb oedema) were managed with a mineralocorticoid receptor antagonist.
- What it means: The proof, in people, that castration-resistant prostate cancer is usually still androgen-driven. It renamed the disease (hormone-refractory became castration-resistant) and it opened the line of drugs that now dominate treatment at every stage from first diagnosis of metastatic disease onwards.
- Caveats: 21 patients in a dose-escalation study with no control arm; the survival evidence came from COU-AA-301 and COU-AA-302.; Prostate-specific antigen decline is a pharmacodynamic signal, not a survival endpoint.; The mineralocorticoid excess is intrinsic to CYP17 blockade and is the reason abiraterone must be given with prednisolone or a mineralocorticoid antagonist, which carries its own long-term cost.

## Sources

- J Clin Oncol 2008: https://doi.org/10.1200/jco.2007.15.9749
- PubMed: https://pubmed.ncbi.nlm.nih.gov/18645193/

## Connected records

- key papers: [Abiraterone in metastatic prostate cancer without previous chemotherapy](https://onco.cc/key-papers/paper-abiraterone-acetate-prostate-n-engl-j-med-2013/), [COU-AA-301: abiraterone and increased survival in metastatic castration-resistant prostate cancer after docetaxel](https://onco.cc/key-papers/paper-cou-aa-301-abiraterone-de-bono-nejm-2011/), [LATITUDE: abiraterone plus prednisone in newly diagnosed high-risk metastatic castration-sensitive prostate cancer](https://onco.cc/key-papers/paper-latitude-nejm-2017/), [Molecular determinants of resistance to antiandrogen therapy](https://onco.cc/key-papers/paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004/)
- roadmaps: [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/)
- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- fronts: [Hormonal Therapy](https://onco.cc/fronts/hormonal/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/)
- drugs: [Abiraterone acetate](https://onco.cc/drugs/abiraterone/)
- institutions: [The Institute of Cancer Research](https://onco.cc/institutions/icr-london/), [The Royal Marsden](https://onco.cc/institutions/royal-marsden/)
- terms: [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [PSA (prostate-specific antigen)](https://onco.cc/terms/psa/)
- people: [Gerhardt Attard](https://onco.cc/people/gerhardt-attard/), [Johann de Bono](https://onco.cc/people/johann-de-bono/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [The valley of death between lab and product](https://onco.cc/bottlenecks/b-translational-valley/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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