Does ADT3 really work? The TARP study

A number of physicians and patients have believed for years that so-called “triple” androgen blockade (ADT3) is a more effective option than an LHRH alone or combined androgen deprivation in the treatment of men with advanced prostate cancer. However, the clinical evidence supporting this belief has been limited.

The so-called “Therapy Assessed by Rising PSA” (TARP) study was initiated in 2007 to investigate this issue in one specific group of men: those who had a rising PSA of between 2 and 20 ng/ml (but no sign of gross metastatic disease) after prior treatment with an LHRH agonist such as leuprolide acetate or goserelin acetate alone.

The TARP study is a randomized, double-blind, multicenter trial in which men with a rising PSA on an LHRH agonist remained on the LHRH agonist but were randomized to receive additional treatment with either bicalutamide + a placebo (combined androgen deprivation or ADT2) or bicalutamide + dutasteride (ADT3).

Bicalutamide is an antiandrogen that blocks the effects of androgens like testosterone in men with prostate cancer but has low affinity for the androgen receptor compared to dihydrotestosterone (DHT). Dutasteride, a dual 5-reductase inhibitor (5ARI), blocks the conversion of testosterone to DHT, reduces tumor volume, and improves PSA in prostate cancer. The theoretical opportunity is that bicalutamide should be a more effective antiandrogen if it competes against intraprostatic testosterone, rather than DHT, for the androgen receptor. The primary endpoint of the TARP study is time to disease progression after at least 18 months of treatment in the two trial arms.

The details of this trial have been discussed in a recent paper by Sartor et al., and it is fully enrolled. Although it is still a relatively small study, TARP is the first randomized, placebo-controlled clinical trial to assess the clinical impact of dutasteride and an antiandrogen in patients failing first-line LHRH analog treatment, and should help us to understand the real potential of ADT3 in reducing the rate of disease progression in patients with non-metastatic, castration-resistant prostate cancer (CRPC). However, we do not expect to see the results of this trial before about 2013, so if you are faced with the decision what to do after a rising PSA on an LHRH agonist, for the time being you are going to have to rely on your own research and a discussion with your doctor.

4 Responses

  1. Using myself as one example, on recurrence of my disease in 1996 my urologist put me on an ADT2 protocol with Lupron and bicalutamide/Casodex. Since it appeared he was leaving me on this protocol indefinitely, my research began. After 5 years on constant ADT2 I moved to a medical oncologist and stopped both drugs. 1.5 years later my PSA began a rapid rise and by 2 years I returned to ADT but this time added dutasteride/Avodart for triple hormonal blockade/ADT3. Nearly instant PSA and T drop to castrate levels, so 1 year later again off the Lupron and bicalutamide/Casodex, BUT this time continued the dutasteride/Avodart to continue inhibiting returning T from converting to DHT. This time it took over 2 years before any rise from <0.01 ng/ml, and in the following 4.5 years my PSA has been on a very slow rise from <0.01 ng/ml to its most recent 1.16 ng/ml. My plan is return to bicalutamide (and possibly Lupron) to accompany my continuing dutasteride/Avodart when my PSA reaches 2.0 ng/ml, but at its current rate of increase, that could be another couple of years. So, for this ADT patient, triple hormonal blockade/ADT3 has worked much more efficiently with the added 5AR inhibitor dutasteride/Avodart than the earlier ADT2 with only Lupron and Casodex.

  2. Forgot to check-mark the “Notify me of follow-up comments via email” so have done so now.

  3. n = 1

  4. True … but then that’s why the TARP study is being carried out.

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