Question
A 67-year-old man comes to the physician because of a 3-month history of urinary urgency, nocturia, and progressive pain in his lower back. The pain is worse at night and does not respond to ibuprofen. Rectal examination shows an enlarged, asymmetric prostate with a nodular surface. Prostate-specific antigen concentration is 11 ng/ml (N < 4). A biopsy of the prostate shows a high-grade adenocarcinoma. A CT scan of the pelvis shows multiple osteoblastic lesions of the lumbar spine. The patient is started on a drug that competes with androgens for interaction with the testosterone receptors. Treatment with which of the following drugs was most likely initiated in this patient?
| A. |
Leuprolide
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| B. |
Flutamide
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| C. |
Degarelix
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| D. |
Docetaxel
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Show Answer
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Correct Answer � B
Explanation
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Ans-B-Flutamide
Leuprolide
GnRH agonists such as leuprolide are commonly used for medical androgen deprivation therapy in the initial treatment of metastatic prostate cancer. When administered continuously, GnRH agonists cause downregulation of the GnRH receptor in the pituitary, which reduces the secretion of gonadotropins (FSH, LH), thereby decreasing the production of androgens in the testes. GnRH agonists do not, however, influence the interaction between androgens and their receptors.
Flutamide
Flutamide is a nonsteroidal competitive inhibitor for the binding of dihydrotestosterone and testosterone to the androgen receptor (i.e., an antiandrogen). The inhibition of androgen receptor stimulation prevents the growth of prostate cancer and its metastases. While antiandrogen monotherapy is an option for androgen deprivation therapy of metastatic prostate cancer, flutamide is most commonly used in combination with GnRH agonists (combined androgen blockade). The simultaneous administration of both drugs prevents the worsening of symptoms (e.g., bladder obstruction, bone pain) that may occur due to a transient rise in testosterone during initial treatment with GnRH agonists.
Degarelix
Degarelix, a GnRH antagonist, binds to GnRH receptors on pituitary gonadotropin-producing cells, immediately suppressing testosterone production. As opposed to GnRH agonists, GnRH antagonists are not associated with an initial disease flare, so they can be used as an alternative androgen deprivation therapy for metastatic prostate cancer. However, they do not influence the interaction between androgens and their receptors.
Docetaxel
Docetaxel is a chemotherapeutic agent that stabilizes polymerized microtubules of the mitotic spindle during anaphase, thereby interfering with mitosis. Docetaxel can be used in combination with androgen deprivation therapy (e.g., GnRH agonists) for the initial treatment of metastatic prostate cancer. However, it does not influence the interaction between androgens and their receptors
