When all the drugs in the same class have the same general clinical impact, this is known as a “class effect.” As an example, all statins (hydroxymethylglutaryl–coenzyme A reductase inhibitors) will lower risk for certain types of cardiovascular event because they lower levels of cholesterol. That is a “class effect.”
Lueteinizing hormone releasing hormone or LHRH agonists (also often referred to as gonadatropin releasing hormone or GnRH agonists) also have “class effects” in that they all lower male testosterone levels and they all induce “hot flashes” (to varying degrees) in nearly all patients. However, just as different statins can have different effects on different patients, it is reasonable to believe that different LHRH agonists may also have different effects in different patients but, as Vilar-González et al. have noted in a recent paper, there is almost no useful, comparative information on the clinical effects of the different LHRH agonists.
So what are the different LHRH agonists that have been shown to lower testosterone levels in men with progressive forms of prostate cancer. There are, in fact, six such agents:
- Leuprolide acetate (Lupron, Eligard, Viadur)
- Goserelin acetate (Zoladex)
- Histrelin acetate (Vantas)
- Triptorelin pamoate (Trelstar)
- Buserelin acetate (Suprefact)
- Deslorelin acetate
Neither buserelin acetate nor deslorelin acetate have ever been approved for the treatment of prostate cancer in the USA. There is also one other LHRH agonist, naferelin acetate (Synarel), which has never been tested for its ability to lower testosterone levels in men with prostate cancer. Note also that some LHRH agonists with different brand names, are in fact the same generic biologic agent. For example, Lupron and Eligard are both widely used brands of leuprolide acetate marketed by different companies around the world.
Why is any of this important? Well, if a patient doesn’t respond well to one LHRH agonist (or if he has really problematic side effects as a consequence of treatment with one particular LHRH agonist), it is possible that he may do better on a different one. Unfortunately, because there have been no direct “head to head” comparisons of these agents, we really don’t know whether there are significant differences between them.
In the USA, the majority of patients receiving an LHRH agonist will receive a form of leuprolide acetate as their first-line LHRH agonist, but it is worth remembering that there are others, and that their effects may be slightly different just as the clinical effects of the various statins are all slighly different. Again, for purposes of comparison, when patients need a statin it is common to start them on one of the older statins (simvastatin or Mevacor). If the effects of simvastatin are insufficient, a patient may be given stronger statins such as atorvastatin (Lipitor) or rosuvastatin (Crestor). Individual patients may have the most appropriate long-term outcomes on any one of these agents.
It would be nice to know whether the differences between the various LHRH agonists were clinically signifciant insubsets of patients, thus allowing more appropriate clinical use of these agents.
It would also be interesting to know whether there were any really clinically significant risks or benefits associated with use of the LHRH antagonist degarelix (Firmagon) instead of one of the LHRH agonists as first-line hormonal therapy.
When all the drugs in the same class have the same general clinical impact, this is known as a “class effect.” As an example, all statins (hydroxymethylglutaryl–coenzyme A reductase inhibitors) will lower risk for certain types of cardiovascular event because they lower levels of cholesterol. That is a “class effect.”
Lueteinizing hormone releasing hormone or LHRH agonists (also often referred to as gonadatropin releasing hormone or GnRH agonists) also have “class effects” in that they all lower male testosterone levels and they all induce “hot flashes” (to varying degrees) in nearly all patients. However, just as different statins can have different effects on different patients, it is reasonable to believe that different LHRH agonists may also have different effects in different patients but, as Vilar-González et al. have noted in a recent paper, there is almost no useful, comparative information on the clinical effects of the different LHRH agonists.
So what are the different LHRH agonists that have been shown to lower testosterone levels in men with progressive forms of prostate cancer. There are, in fact, six such agents:
Neither buserelin acetate nor deslorelin acetate have ever been approved for the treatment of prostate cancer in the USA. There is also one other LHRH agonist, naferelin acetate (Synarel), which has never been tested for its ability to lower testosterone levels in men with prostate cancer. Note also that some LHRH agonists with different brand names, are in fact the same generic biologic agent. For example, Lupron and Eligard are both widely used brands of leuprolide acetate marketed by different companies around the world.
Why is any of this important? Well, if a patient doesn’t respond well to one LHRH agonist (or if he has really problematic side effects as a consequence of treatment with one particular LHRH agonist), it is possible that he may do better on a different one. Unfortunately, because there have been no direct “head to head” comparisons of these agents, we really don’t know whether there are significant differences between them.
In the USA, the majority of patients receiving an LHRH agonist will receive a form of leuprolide acetate as their first-line LHRH agonist, but it is worth remembering that there are others, and that their effects may be slightly different just as the clinical effects of the various statins are all slighly different. Again, for purposes of comparison, when patients need a statin it is common to start them on one of the older statins (simvastatin or Mevacor). If the effects of simvastatin are insufficient, a patient may be given stronger statins such as atorvastatin (Lipitor) or rosuvastatin (Crestor). Individual patients may have the most appropriate long-term outcomes on any one of these agents.
It would be nice to know whether the differences between the various LHRH agonists were clinically signifciant insubsets of patients, thus allowing more appropriate clinical use of these agents.
It would also be interesting to know whether there were any really clinically significant risks or benefits associated with use of the LHRH antagonist degarelix (Firmagon) instead of one of the LHRH agonists as first-line hormonal therapy.