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Investigational Oral Androgen Receptor Antagonist Shows Promising Antitumour Activity in Both Chemotherapy-Naïve and Post-Chemotherapy Patients With Prostate Cancer: Presented at EMUC

By Chris Berrie

BARCELONA, Spain -- November 30, 2009 -- The investigational oral androgen receptor antagonist MDV3100 shows promising antitumour activity for both chemotherapy-naïve and post-chemotherapy patients with advanced prostate cancer, and is safe and well tolerated, researchers noted at the 2nd European Multidisciplinary Meeting on Urological Cancers (EMUC).

"The currently available antiandrogens, including bicalutamide, lose their clinical activity -- and in some cases exacerbate or worsen the problem," noted Mohammad Hirmand, MD, Medivation Inc., San Francisco, California, presenting his study here on November 29.

The aim of this trial was to investigate the antitumour activity of MVB3100 in patients with castration-resistant prostate cancer (CRPC), measured by prostate-specific antigen (PSA) levels, soft-tissue and osseous disease, and circulating tumour cells (CTC).

Patients were initially enrolled in sequential cohorts of 3 to 6 patients, at doses of MVB3100 that ranged from 30 to 600 mg/day. With initial safety established, enrolment was expanded for MVB3100 doses of greater than 60 mg/day, to a total of 140 patients.

With a median PSA level at trial entry of 50 ng/mL, all 140 subjects had undergone prior hormone therapy (1 line, 23%; 2 lines, 30%; 3 lines or more, 47%) and 46% were chemotherapy-naïve (naïve vs post-chemotherapy). The metastasis distribution indicated soft-tissue disease in 66% of patients and osseous disease in 78%.

Following treatment with MVB3100, PSA decreases of more than 50% from baseline were seen in 62% of the naïve patients, and 51% of those post-chemotherapy.

Partial responses and stable disease for soft-tissue disease were seen in 36% and 44% of the naïve patients, respectively, and 12% and 53% of the post-chemotherapy patients. With bone scans at week 12 for 41 naïve subjects and 68 post-chemotherapy patients there was evidence of radiographic stabilisation in 63% and 51% of these patients, respectively.

In the naïve patients, the median times to PSA and radiographic progression were not reached, while for the post-chemotherapy patients, these parameters were met at 186 and 201 days, respectively.

For the 60 naïve patients assessed for CTC, while 91% of those with favourable pretreatment counts (<5 CTC /7.5 mL blood) remained favourable post treatment, 75% saw a conversion from unfavourable pretreatment counts (>=5 CTCs /7.5 mL blood) to favourable post-treatment counts.

Similarly, for the post-chemotherapy patients, the 91% of those with favourable pretreatment counts were maintained post treatment, and there was a smaller conversion from unfavourable pretreatment to favourable post treatment (37%).

In the safety and tolerability analysis, the most frequently reported adverse event was fatigue, whereas for grade 3 disease there was an MVB3100 dose-dependent increase, which reached 20% of patients at MVB3100 480 mg/day. Two patients who witnessed seizures were known to be on medications that can cause seizures.

MDV3100 is a promising candidate for the treatment of prostate cancer, with a maximum tolerated dose selected at 240 mg/day. Phase 3 trials will now begin.

Funding for this study was provided by Medivation Inc, USA.

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: Antitumour Activity of MDV3100 in a Phase 1-2 Study of Advanced Prostate Cancer. Oral abstract O3]

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