Bicalutamide

Bicalutamide (molecular formula: C18H14F4N2O4S), is an oral, high-affinity and selective androgen receptor antagonist. It binds to the receptor somewhat less strongly than e.g. apalutamide. The half-life is about 7 days.

Bicalutamide is approved for the treatment of adult men either as sole therapy or adjuvant to radical prostatectomy or radiotherapy in patients with locally advanced prostate cancer and a high risk of progression.

Bicalutamide is a selective androgen receptor (AR) inhibitor that binds directly to the ligand-binding domain of the receptor. This prevents the docking of its natural ligand (testosterone) and the transcription mediated by it. Bicalutamide reduces the proliferation of tumour cells, increases apoptosis and thus has an antitumoral effect.

Very common side effects include enlargement of the mammary gland, breast tenderness, hot flashes, constipation, pelvic pain, back pain, general pain and weakness. Kidney dysfunction can occur, as can liver dysfunction, liver failure

Diseases of the skin and subcutaneous tissue: very common: exanthema ; frequent: alopecia, hair regrowth/hirosutism, dry skin, pruritus

Rare: photosensitivity

Also: anaemia, diabetes mellitus, pain, chills, diarrhoea, nausea, vomiting, rapid fatigue, somnolence, insomnia, sleep disturbances, dizziness.

Bicalutamide is a potent enzyme inducer, for example of CYP3A4, -2C19 and -2C9, and drug transporters such as PGP are induced. It can therefore influence the efficacy of numerous drugs. Simultaneous use with warfarin and coumarin-like anticoagulants should be avoided.

With 60,000 new cases every year, one in four malignant tumours diagnosed in men is prostate carcinoma. As long as the prostate carcinoma is localized, androgen deprivation therapy (ADT, hormone blockade, chemical castration) is usually given in addition to radiation treatment. If the blood level of the marker protein PSA continues to rise, the tumour is considered resistant to castration. In this situation, tumour cells can produce increased amounts of androgens themselves or, after amplification and mutation of the androgen receptor gene or through altered cofactors of the androgen receptor, can also use very low androgen concentrations for increased tumour growth.

In the past, it was recommended to wait and see in the case of prostate carcinoma with low symptomatic disease without evidence of metastases while maintaining conventional androgen deprivation therapy. For these patients, non-steroidal androgen receptor inhibitors such as bicalutamide represent a well-validated option that significantly delays the time to metastasis and prolongs survival.

Non-steroidal antiandrogens were first discovered in the 1970s. The first active ingredient in this group of substances, flutamide, was approved in the USA in 1989. Flutamide is broken down comparatively quickly. With the successor bicalutamide, an active ingredient was approved in the USA in 1995 which has a much longer duration of action and is also better tolerated by the liver. There are numerous low-cost generics containing the active ingredient bicalutamide.

1. Carswell CI et al (2002) Bicalutamide: in early-stage prostate cancer. Drugs, 2002, 62(17), 2471-79
2. Chi KN et al (2019) Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 381: 13-24
3. Moul JW et al(2015) Hormones naïve prostate cancer: predicting and maximizing response intervals. Asian J Androl 17: 9290-9235
4. Scher HI et al(2015) Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model. PLoS One 10: d0139440
5. Smith MR et al (2018) Relationship of time to metastasis (TTM) and site of metastases in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Results from the phase 3 SPARTAN trial. J Clin Oncol 36 (suppl; abstr 5033) & Poster Session, ASCO 2018, Abstract 5033: meetinglibrary. asco.org/record/163132/abstract.