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Traditionally, anti-androgen medications have been used in combination with LHRH agonists to block testosterone. When anti-androgens are used alone it is called anti-androgen monotherapy. This approach is attractive for some men because it causes in a milder degree of testosterone blockade with less side effects. There are three anti-androgen agents – Casodex, Flutamide, and Nilutamide. They work by keeping testosterone away from the androgen receptor, an enzymatic “switch” inside the prostate cancer cell. This switch stimulates cell growth when it’s turned on. Anti-androgens keep the switch in the “off” position. Because anti-androgens do not eliminate testosterone altogether, they have fewer side effects than the LHRH agonists such as Lupron, Trelstar, Eligard and Zoladex.
Clinicians with experience using Casodex monotherapy estimate that Casodex monotherapy is about 70% as effective as the LHRH agonists but with only 30% of the toxicity. Anti-androgens have been studied in prospective randomized trials as stand-alone therapy and combined with radiation. Overall, compared to LHRH agonists, side effects are certainly less. And compared to placebo, they clearly retard prostate cancer growth. The only caveat with Casodex monotherapy is a higher risk of breast growth. This can be partially or completely prevented with prophylactic breast radiation or an estrogen blocking pill called Femara.
Quality of Life
Whenever the action of testosterone is inhibited, side effects ensue–hot flashes, osteoporosis, loss of muscle and loss of libido are typical. Many other side effects can also occur. Casodex monotherapy is less likely to induce muscle loss and less likely to reduce libido than the LHRH agonists. For example, only about 50% of younger men lose their libido whereas about 80% of men lose their libido with LHRH agonists.
There is one side effect that is more common with Casodex monotherapy than with LHRH agonists – breast enlargement. The medical term is gynecomastia. Gynecomastia occurs in 10% to 20% of men treated with LHRH agonists and in 50% to 60% of men on AAM. Gynecomastia can be prevented with radiation or an estrogen blocking pill called Femara. However, once breast tissue develops, it can only be removed with liposuction or surgery. To be effectively prevented, the radiation or the Femara must be started prior to starting treatment.
Length of Life
The attraction of Casodex monotherapy is fewer side effects. But to what degree do we sacrifice anti-cancer effectiveness and long-term survival? Studies performed to answer to this question have various flaws. For example, low-dose Casodex (50 mg daily) has been compared with LHRH agonists in men with advanced metastatic prostate cancer. Survival was shorter in men treated with low-dose Casodex compared to men who received Lupron or Zoladex.
Higher doses of Casodex (150 mg daily) have been compared with Zoladex, a LHRH agonist, in men with fairly advanced cancer that had not quite yet spread to the bones. After six years, men treated with Zoladex lived an average of six months longer than the men treated with Casodex 150 mg daily. However, the statisticians were concerned that there were an insufficient number of participants for the trial to be conclusive. Similar conclusions have been drawn from another study in men with advanced metastatic disease.
Practical Considerations
The side effects of Casodex monotherapy are less than with LHRH agonists. However, in regards to anti-cancer effectiveness, it is possible, even likely, that Casodex alone is somewhat less effective in controlling cancer than the LHRH agonists. LHRH agonists should be considered standard when cure is the goal. For example, when testosterone blockade is given in conjunction with surgery or radiation or when younger patients relapse soon after surgery or radiation with fast PSA doubling times. On the other hand, Casodex monotherapy is a good choice for older patients or men who are less tolerant of side effects and need milder treatment to maintain quality of life.
Various testosterone inactivating pharmaceuticals (TIP) are used to treat prostate cancer. This post addresses Casodex (Bicalutamide) as a stand-alone therapy with the goal of reducing side effects commonly associated with …