Pharmacology Update

Histrelin Implant (Vantas)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved a long-acting implant for the palliative treatment of prostate cancer. The implant is a sterile non-biodegradable (hydrophilic polymer), diffusion-controlled reservoir delivery system that releases the histrelin for 12 months. Histrelin is a peptide agonist of luteinizing hormone-release hormone (LHRH). The product is marketed by Vantas Pharma as Vantas. This implant joins another 12-month LHRH agonist implant, leuprolide acetate (Viadur).

Indications

Histrelin implant is indicated in the palliative treatment of advanced prostate cancer.1

Dosage

One implant is inserted for 12 months. The optimal site is approximately half way between the shoulder and elbow in the crease between the bicep and triceps. The implant delivers 50-60 mg daily.1

Potential Advantages

The implant provides continuous LHRH therapy over 12 months independent of the patient’s compliance. The non-biodegradable implant allows it to be removed if necessary because of adverse events or intolerance.

Potential Disadvantages

The implant extruded through the incision site in 8/171 patients in the clinical trials.1

Comments

Histrelin implant maintains castrated testosterone levels (50 ng/dL) from week 4 to at least week 52. The mean serum testosterone level was 15 ng/dL at week 4 and 14.3 ng/dL at week 52. Serum prostate specific antigen decreased from baseline to normal range in 93% of patients. A spike in testosterone level occurred on day 2 and decreased to below baseline levels by week 2.1 A transient spike in testosterone levels early in treatment is common with other LHRH antagonists as well. Patients may also experience worsening of symptoms, and onset of new symptoms. These may include bone pain, neuropathy, hematuria, or urethral or bladder outlet obstruction.1 Antiandrogen therapy (eg, flutamide) may be used to prevent or attenuate this transient or flare phenomena.2,3 About 14% of patients experienced local or insertion site reactions.1 Histrelin implant is a hydrophilic polymer cartridge while the leuprolide acetate implant is a nonbiodegradable osmotically driven delivery system. There are currently no published comparative studies although the safety and efficacy of leuprolide appear to be similar.3 The cost of the histrelin implant was not available at the time of this review. As a point of reference, the wholesale cost of the leuprolide implant is $4547.

Clinical Implications

LHRH agonists (eg, leuprolide, goserelin, histrelin) are important treatment option for advanced prostate cancer. It is, however, more expensive than orchiectomy. Both leuprolide and histrelin implant provide drug delivery for 12 months. Prospective studies are ongoing to assess the relative merits of intermittent versus continuous androgen blockage.4

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.

References

1. Vantas Product Information. Valera Pharmaceuticals, Inc. October 2004.

2. Chertin B, et al. J Urol. 2000;163:838-844.

3. Fowler JE, et al J Urol. 2000;164:730-734.

4. Lablaw DA, et al. J Clin Oncol. 2004;22:2927-2941.