Flutamid

Flutamide (molecular formula: C11H11F3N2O3) is an oral, non-steroidal anti-androgen agent (androgen receptor antagonist) belonging to the group of targeted tumor therapeutics from the family of androgen receptor blockers. 10 metabolites have been identified. The main metabolite is the active 2-hydroxyflutamide, which is predominantly formed via CYP 1A2. Flutamide has a nitroaromatic structure and is used for the treatment of prostate carcinoma.

Flutamid prevents the antagonization of the androgen receptor in the hypothalamus and the anterior pituitary gland, thus interrupting the control loop of the testosterone/DHT-mediated negative feedback. As a result, LH release from the anterior pituitary and testosterone synthesis in the testes increase. By blocking the androgen receptor, however, the effect of the male sex hormones is cancelled. Flutamide interferes several times in the signal transduction by the androgen receptor: it prevents its translocation into the nucleus, inhibits the binding to DNA and thus the androgen-mediated transcription. In this way, the proliferation of tumour cells is reduced and apoptosis is increased.

Initial treatment in combination with other drugs: advanced hormone-dependent prostate cancer and in patients already treated with drugs to control sex hormone production

As sole treatment: Advanced, hormone-dependent prostate carcinoma after testicle removal

Advanced, hormone-dependent prostate cancer if other treatments have not responded or have not been tolerated;

Adjuvant therapy of localized prostate cancer (stage B2-C) in combination with an LHRH agonist and appropriate radiotherapy

Common with monotherapy with flutamide:

• Gynecomastia, mastodynia sometimes accompanied by galactorrhea (less common when combined with a drug that inhibits hormesis); diarrhea, nausea, vomiting, flushing, loss of libido, erectile dysfunction, impaired liver function, increased appetite, fatigue, insomnia

Common when combined with an LH-RH agonist:

• Hot flashes, decreased libido, fertility dysfunction, diarrhea, nausea, vomiting.
• Diarrhea (more common when combined with a drug that inhibits hormesis), nausea, vomiting, increased appetite, insomnia, fatigue, transient impaired liver function, and hepatitis.

Occasional:

• Small-nodule changes of the mammary gland body (reversible after discontinuation of treatment).

Rare:

• Cardiovascular disorders, edema, lymphatic congestion, hematoma formation, zoster, pruritus, lupus-like syndrome.

Furthermore:

• Headache, flushing, dizziness, weakness, malaise, blurred vision, thirst, chest pain, anxiety, depression, loss of scalp hair and muscle cramps, increase in blood creatinine levels.

In combination with an agent inhibiting hormone formation were additionally observed:

Rarely:

• Anemia (hemolytic anemia, megalocytic anemia, methemoglobinemia, sulfhemoglobinemia), leukopenia, thrombocytopenia, hypertension, icterus;
• Central nervous system: drowsiness, confusion, nervousness.
• Photosesibility: appearance of skin symptoms after exposure to light with lupus erythematosus-like symptomatology (Kaur C et al. 2003).
• Toxic liver injury (rarely fatal) (Giorgetti R et al 2017).

FLUTA-cell® 250 mg tablets ; Flutamid AL 250 ^®; Flumid®; Fugerel®;

1. Azhagiya Singam ER et al (2019) Structural Dynamics of Agonist and Antagonist Binding to the Androgen Receptor. J Phys Chem B 123: 7657-7666.
2. Giorgetti R et al (2017) Flutamide-induced hepatotoxicity: ethical and scientific issues. Eur Rev Med Pharmacol Sci 21(1 Suppl):69-77.
3. Hejmej A et al (2018) The effects of flutamide on cell-cell junctions in the testis, epididymis, and prostate. Reprod Toxicol 81:1-16.
4. Iguchi T et al (2019) Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: study protocol for a multicenter randomized phase II trial (the OCUU-CRPC study). BMC Cancer 19:339.
5. Kaur C et al (2003) Flutamide-induced photosensitivity: is it a forme fruste of lupus? Br J Dermatol 148: 603-604.