Common dilemmas in kids

2015

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Benefits of less frequent injections in advanced prostate cancer

Volume 44, No.6, 2015 Pages 429-430

Michael Ortiz

Leuprorelin is indicated for the palliative treatment of advanced prostate cancer (APC) and is available as 1, 3, 4 and 6-monthly injections. There are advantages of longer leuprorelin injection intervals in the treatment of APC. Across all injection intervals, efficacy is similar and the majority of patients achieve testosterone suppression and normalisation of prostate-specific antigent. Treatment is well tolerated. Six-monthly leuprorelin injections are less costly to the healthcare system than the shorter interval injections.

Even though there is a trend towards earlier detection of prostate cancer, unfortunately, many men are not diagnosed until it has progressed to the later stage, known as advanced prostate cancer (APC). Hormone therapy, also called androgen deprivation therapy, can slow or stop the growth of prostate cancer by stopping the production of testosterone, which prostate cancer cells usually depend on for growth.

More than 80% of men with APC benefit from this treatment, reflected by reduced serum postate-specific antigen (PSA) levels.1 A rise in PSA levels following initial prostate cancer treatment can indicate cancer recurrence.2

There are two main approaches to hormone therapy: a surgical procedure to remove the testicles (orchidectomy) or medication to ‘switch off’ testosterone. Leuprorelin is used for palliative treatment of APC and is available as 1, 3, 4 and 6-monthly injections. Are there advantages of giving leuprorelin injections less frequently to patients with APC?

A review of long-acting injections for APC in the US3 found there were no differences between the injection intervals based on efficacy. However, they did find differences in the availability of long-acting formulations, dosage forms, administration techniques, ease of preparation, storage and handling.3

Efficacy, in terms of serum testosterone suppression and normalisation of PSA, has been shown to be similar for 1, 3, 4 and 6-month injection intervals (Table 1). More common adverse events of hot flushes and fatigue seem to be similar with a slight increase in the proportions of moderate hot flushes with longer interval injections.

Table 1. Comparison of leuprorelin treatment by injection interval

 

1-monthly

3-monthly

4-monthly

6-monthly

Strength

7.5 mg

22.5 mg

30 mg

45 mg

PBS repeats

5

1

1

1

Mean serum testosterone at 28 days (SD)5,7–9

6.1 (4.3)

10.1 (0.7)

12.4 (0.8)

12.3 (2.1)

Mean PSA levels at 28 days (SD)5,7–9

3.2 (1.2)

1.7 (0.5)

1.3 (0.3)

1.2 (0.3)

Drug cost per script*

$420.54

$1108.97

$1451.54

$2124.19

Administration frequency per year

12

4

3

2

Drug cost per year

$5046.48

$4435.88

$4354.62

$4248.38

Costs per administration

$36.30

$36.30

$36.30

$36.30

Total administration cost

$435.60

$145.20

$108.90

$72.60

Total cost per year

$5482.08

$4581.08

$4463.52

$4320.98

Difference from 6-monthly injections

$1161

$260

$142

 

PBS leuprorelin scripts in 2013

3660

15,641

8804

3079

Patients treated with formulation§

305

3910

2934

1540

Savings per year

$354,105

$1,016,665

$419,657

 

*Drug Cost March 2014 PBS book, Schedule of Pharmaceutical Benefits, www.pbs.gov.au/publication/schedule/2015/04/2015-04-01-general-schedule.pdf; Administration cost MBS schedule item 23; 2013 PBS script counts from the Medicare Australia Website, http://medicarestatistics.humanservices.gov.au/statistics/mbs_item.jsp; §Number of patients was estimated by dividing the number of scripts by the number of administrations per year

PBS, Pharmaceutical Benefits Scheme; PSA, Prostate-specific antigen

A study by Tunn found Italian urologists choose 6-monthly leuprorelin injections because of the longer dosing interval (90%), small injection volume of ≤0.5 ml (20%) and short needle size of pre-filled syringe (15%).4

The interval between injections affects the number of consultations with a healthcare practitioner. In addition, the Pharmaceutical Benefits Scheme (PBS) listing for longer interval injection products (3, 4 and 6-monthly) is for one injection and one repeat. This means that 3-monthly injections require two scripts a year, while 6-monthly injections require just one script per year. The less frequent injection means patients have fewer trips to the pharmacy and doctor.

An economic analysis in nine European countries showed monthly leuprorelin injections was the most expensive treatment option, whereas 6-monthly injections offered cost savings.5 The savings stemmed primarily from reduced resource utilisation (ie fewer visits required for less frequent injections). The savings were greatest in countries with the highest costs associated with visits (Belgium and Portugal), but cost savings could still be achieved in the country with the lowest visit reimbursement level (Poland). The size of savings was directly related to costs of treatment visits.5

A similar economic analysis using costs in Australia found the common 4-monthly leuprorelin injections (34% of patients) and 3-monthly injections (45% of patients) were more costly when compared with 6-monthly injections ($142 and $260 per year respectively; Table 1). Monthly injections cost $1161 more per year when compared to 6-monthly injections (Table 1). Significant savings to the healthcare system of $1.8 million per year could be achieved by converting 1, 3 and 4-monthly injection patients to 6-monthly injections (Table 1).

Market research of 200 European men with prostate cancer4 found maintaining lifestyle during treatment was important for the majority (83%). Sixty-eight per cent preferred 6-monthly injections over 1 or 3-monthly injections and nearly half (with 81% aged ≤ 70 years of age) believed a 6-monthly injection could improve their quality of life.6

There are some advantages to giving shorter interval leuprorelin injections. Some patients do need regular PSA measurement to monitor for leupoprelin-resistance disease. If patients visit their GPs more than once every 3–4 months, the cost savings for the longer interval might not be as large.

Overall, the advantages of longer injection intervals include minimal disruption to patient lifestyle during treatment and a decreased cost to the healthcare system. However, longer durations between injections may mean patients are assessed less frequently by a medical practitioner. The final choice should therefore be discussed with the patient, taking the risks and benefits of longer injection intervals into account.

Competing interests: Michael Ortiz has received payment for consultancy from ABBVIE, AstraZeneca and Tolmar (who manufacture 1, 3, 4 and 6-monthly injectable treatments for APC), as well as various other pharmaceutical companies. He has also consulted on pricing and reimbursement with multiple pharmaceutical, medical device and diagnostic companies over the last 5 years. No payment has been received for writing this article.
Provenance and peer review: Not commissioned, externally peer reviewed.

References

  1. Stricker P. Advanced prostate cancer. Available at www.phillipstricker.com.au/your-treatment/advanced-prostate-cancer [Accessed 13 May 2015].
  2. Cancer Research UK. About hormone therapy for prostate cancer. London: CRUK, 2014. Available at www.cancerresearchuk.org/about-cancer/type/prostate-cancer/treatment/hormone/about-hormone-therapy-for-prostate-cancer [Accessed 13 May 2015].
  3. Department of Veterans Affairs, Pharmacy Benefits Management Service (VA PBM), VA Medical Advisory Panel (VA MAP). VA/DoD Drug Class Review: Luteinizing Hormone Releasing Hormone (LHRH) Agonists in Prostate Cancer. Update November 2007 and June 2010. Washington, DC: US Department of Veterans Affairs, 2010.
  4. Tunn UW. A 6-month depot formulation of leuprolide acetate is safe and effective in daily clinical practice: A non-interventional prospective study in 1273 patients. BMC Urol 2011;11:15–20.
  5. Perez-Marreno R, Chu FM, Gleason D, Loizides E, Wachs B, Tyler RC. A six-month, open-label study assessing a new formulation of leuprolide 7.5 mg for suppression of testosterone in patients with prostate cancer. Clin Ther 2002;24:1902–14.
  6. Schulman C. Assessing the attitudes to prostate cancer treatment among European male patients. BJU Int 2007;100(Suppl 1):6–11.
  7. Chu FM, Jayson M, Dineen MK, Perez R, Harkaway R, Tyler RC. A clinical study of 22.5 mg La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. J Urol 2002;168:1199–203.
  8. Sartor O, Dineen MK, Perez-Marreno R, Chu FM, Carron GJ, Tyler RC. An eight-month clinical study of LA-2575 30.0 mg: A new 4-month, subcutaneous delivery system for leuprolide acetate in the treatment of prostate cancer. Urology 2003;62:319–23.
  9. Crawford ED, Sartor O, Chu F, Perez R, Karlin G, Garrett JSe. A 12-month clinical study of LA-2585 (45.0 mg): A new 6-month subcutaneous delivery system for leuprolide acetate for the treatment of prostate cancer. J Urol 2006;175:533–36. 

Correspondence afp@racgp.org.au

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