Source: DGNews  |  Posted 2 years ago

By Chris Berrie

BARCELONA, Spain -- December 1, 2009 -- Abiraterone acetate (AA) can be safely
administered for long periods without concurrent steroids in patients with
advanced castration-resistant prostate cancer (CRPC), according to research
presented here at the 2nd European Multidisciplinary Meeting on Urological
Cancers (EMUC).

AA reduces levels of testosterone, oestradiol, and cortisol, but it increases
levels of adrenocorticotropic hormone, deoxycorticosterone, and corticosterone,
which could lead to hypokalaemia, hypertension, and fluid retention. To
investigate these potential toxicity problems, a retrospective analysis was
undertaken of 102 patients with advanced CRPC who were enrolled in 4
prospective phase 1 and 2 clinical trials at the Royal Marsden Hospital,
Sutton, Surrey, United Kingdom.

Of these subjects, 68.6% were included in the analysis, as 70 patients remained
on their AA treatment with or without steroids for over 6 months, noted
coinvestigator Diletta Bianchini, MD, Royal Marsden Hospital, speaking here on
November 29.

At baseline, subjects were Eastern Cooperative Oncology Group performance
status 0 (48.5%), 1 (44.2%), and 2 (4.2%); about two-thirds (65.7%) were
docetaxel naïve. The median age of subjects was 70 years.

At a median follow-up of 22.5 months, subjects demonstrated a median AA
treatment duration of 14 months; most were on AA 1,000 mg/day (87.1%), with 250
mg/day (4.2%), 750 mg/day (5.7%), and 2,000 mg/day (2.8%) also used.
Dexamethasone use was at 0.5 mg once daily, with a median duration of treatment
of 420 days; however, as Dr. Bianchini noted, “about 70 out of the [original]
102 patients did not receive dexamethasone at the beginning of treatment.”

This toxicity analysis showed 60% of patients experiencing hypertension on
treatment, although 25 (42%) of these had controlled hypertension at baseline.
The toxicity grading indicated 50% as grades 1/2, with 10% grade 3, and no
grade 4/5 hypertension. Hypokalaemia was also experienced by 56% of patients,
as 50% grades 1/2, with 6% grade 3, and no grade 4/5. Hypertension and
hypokalaemia were managed with eplerenone (50 to 200 mg/day).

Three patients experienced cardiovascular events during treatment: 1 congestive
heart failure (grade 3; history of prior myocardial infarction [MI],
cerebrovascular disease, hypertension and deep vein thrombosis, with
mitoxantrone treatment), 1 MI (grade 4; multivessel coronary artery stenosis
after 2 weeks of AA, with treatment continuation after stenting), and 1 fatal
pulmonary embolism (grade 5; prior hypertension, diabetes, and left ventricular
dysfunction; died after rapid onset dyspnoea and oedema).

There were also 5 fractures (1 not pathological). The most common metabolic
toxicities of hyperglycaemia (58.5% grades 1/2) and weight gain (25.7% grades
1/2) occurred after introduction of dexamethasone. Median cholesterol and
triglyceride levels did not change significantly with AA treatment.

Dr. Bianchini concluded that “abiraterone is a safe drug, is well tolerated,
and delayed toxicity is uncommon in this patient population.” Dr. Bianchini
added that AA could be safely administered for long periods without concurrent
steroids, although he called for further follow-up on delayed toxicity.

Funding for this study was provided by Cougar Biotechnology Inc.

EMUC was co-organised by the European Association of Urology (EAU), the
European Society for Medical Oncology (ESMO), and the European Society for
Therapeutic Radiology and Oncology (ESTRO).

Presentation title: Long-Term Safety and Tolerability of
Abiraterone Acetate (AA) in Advanced Castration-Resistant Prostate Cancer
(CRPC). Abstract 004