EP. 2B: Clinical Perspectives on the Use of Leuprolide Acetate and Leuprolide Mesylate

In this new Urology Medical Perspectives series, “Expert Perspectives on Advanced/Metastatic Prostate Cancer,” key opinion leaders in the management of hormone-sensitive or castration-resistant prostate cancer reflect on the evolving treatment landscape, including key considerations about the using leuprolide-containing therapeutic combinations. Given the availability of multiple leuprolide formulations, it is essential that clinicians consider key benefits and challenges associated with each option. In the following interview, Brenda Heath, RN, builds a lively discussion concerning practical considerations in using different leuprolide acetate and leuprolide mesylate formulations in patients with prostate cancer.

Urology Times^®: What are the available leuprolide formulations and their recommending dosing strategies and routes of administration? Can you start by describing leuprolide acetate and its associated benefits and challenges?

HEATH: Leuprolide acetate is dosed in different increments. There [are] 1-month, 3-month,4-month, and 6-month doses. [It is available as] a subcutaneous (SC) version and an intramuscular (IM) version. Having the different dose ranges is very helpful [for] coordinating appointments with patients and [ensuring that they come] in for [injections] at appropriate times. Leuprolide acetate [has 2 components] that have to be mixed [to form] the product that is administered to the patient. One version does not need to be refrigerated, [but] the other version [needs refrigeration]. The [refrigerated] version has 2 separate vials [with contents] that need to be mixed … it is important to make sure that we remove [them from refrigeration] 30 minutes before [mixing]. It makes it much easier to mix together, and it's best practice for the patient [to] decrease any stinging or pain. The leuprolide acetate [that needs no refrigeration] is stored at room temperature. The mixing is a little bit different—it's filled in 1 syringe, and you just have to push the plunger up to mix the liquid and the powder together and[then] twirl [it] while it's sitting upright. They are a little bit different, for sure.

Urology Times^®: Can you talk about leuprolide mesylate?

HEATH: Leuprolide mesylate is new to the market here, and we're very excited about this medication. [It requires only] 1 dose, which could be a limiting factor in [using] it; however, it is already prefilled [and] premixed. It [must be] refrigerated, so it [needs] to be removed from the refrigerator 30 minutes ahead of [administration]. However, [it’s] very convenient when [we're] running an advanced prostate cancer clinic day, and [we] have a whole list of patients coming in. [It’s] convenient for the nurses to be able to pull that and already have it premixed.

Urology Times^®: What other challenges do the pharmacy and nursing teams encounter with the various leuprolide formulations?

HEATH: Refrigeration is probably one of the biggest ones. Making sure [that] the appropriate leuprolide acetate and leuprolide mesylate are removed from the [refrigerator] 30 minutes ahead of time can be difficult and challenging to complete with a full schedule. However, [we] are also factoring in the mixing and the premixed injectables and different doses that can come into play. Having [those] 1-, 3-, 4-, [and] 6-month doses can be important as opposed to just the 6-month dose, especially when we have patients who are going to Florida—we may want to meet up with them [in the summer] and give them a 4-month [dose] so that we can give them a 6-month [dose] in November. By the time they return, they are appropriately due for their next injection.

Urology Times^®: Can you speak to the clinical data for each of the leuprolide formulations? Did they differ at sustaining suppressed serum testosterone levels? Are they the same or different?

HEATH: They're pretty similar at sustaining the testosterone levels. They are all agonists, so they all have that potential tumor flare in the beginning. However, they all seem to work comparably at maintaining the testosterone at castrate levels. As long as that testosterone is castrate, their PSA (prostate-specific antigen) suppression is usually pretty good, but, as we know in this day and age, depending on the disease space and the disease that the patient has, we are typically mixing this with another oral oncolytic to keep that PSA [level] down. We are rarely utilizing just leuprolide acetate or leuprolide mesylate as a monotherapy unless it is [given as adjuvant therapy] with radiation.

Urology Times^®: How do the adverse event (AE) profiles compare across the different formulations of leuprolide?

HEATH: I'd definitely say the [AEs] are pretty similar, the top 2 being hot flashes and fatigue. However, they can differ in how they're administered. [For] the leuprolide acetate that's administered IM … I have patients who don't really complain about the IM injections. [This drug and administration route] don't [cause] any site irritation [or] lump. [In comparison], the leuprolide acetate or the leuprolide mesylate that is administered via SC [injection] to the abdomen can cause a little discomfort [and] some stinging. There can be a bump at the site of administration. Those are the differences that … account for the different medications.

Urology Times^®: What clinical and nonclinical factors inform your choice of leuprolide formulation? Do you feel that some formulations of leuprolide are easier to use than are others?

HEATH: Clinically, it depends on the dosing. Some physicians like to start out with a lower dose of leuprolide … and make sure that the [patient isn’t] going to have any AEs and [that] they're going to tolerate it well. Obviously, the most important thing … is making sure that the patient is at a castrate level, so testosterone castration and suppression of the PSA [are] the highest and most important [priorities] that we're looking for with these medications. Clinically, we're looking for testosterone castration and appropriate dosing for a patient [who] is going to be going out of town or [whose] physician wants to start at a lower dose and then increase to a higher dose.

Having the prefilled syringe [of leuprolide mesylate] is definitely much more convenient for the flow of the schedule. That is huge—just being able to pull that medication out ahead of time and administer it when it's already premixed. However, once again, the refrigeration can come into play, [so we should] make sure [that we remove] it from [the refrigerator] 30 minutes ahead of time, especially if [we need to give] multiple injections that day. That can come into play, as well. The main considerations are [whether the formulation is] premixed [and] refrigerated [or needs] mixing and [is] nonrefrigerated.

Transcript has been edited for clarity.