Abstract
To determine whether needle size influences a patient's perception of pain, 50 patients requiring hormonal manipulation for prostate cancer were blindfolded and randomised to receive two goserelin ('Zoladex') or two leuprorelin ('Prostap') injections, using 16- or 23-gauge needles, respectively. Median visual analogue scale pain scores for the first injections of goserelin and leuprorelin were below the level of clinical significance and were not statistically different. Mean administration time for goserelin was significantly shorter than for leuprorelin. In conclusion, there was no statistically significant difference in pain experienced on injection of goserelin and leuprorelin when patients were unaware of needle size.
Keywords: goserelin acetate, leuprorelin acetate, luteinising hormone-releasing hormone analogue, needle size, injection pain
Introduction
Healthcare statistics have revealed that prostate cancer is the most common male cancer in developed countries and the third most common in men worldwide, in terms of the number of new cases.1 Hormonal therapy is now considered a standard treatment option for patients with prostate cancer. The use of luteinising hormone-releasing hormone (LH-RH) analogues, such as goserelin acetate ('Zoladex', AstraZeneca) and leuprorelin acetate ('Prostap', Wyeth), in patients with advanced prostate cancer, is supported by evidence from several randomised clinical trials.2, 3, 4 Goserelin acetate has also shown efficacy in the adjuvant setting5, 6, 7, 8, 9 and as neoadjuvant therapy to radical prostatectomy10, 11 and radiotherapy.12
LH-RH analogues are available in a range of different formulations. Goserelin acetate is available as a 1-month (3.6 mg) or 3-month (10.8 mg) formulation and is administered subcutaneously in a single step as a solid depot, in a ready to use, sterile, prefilled syringe, with a 16-gauge (3.6 mg) or 14-gauge (10.8 mg) needle.13 Leuprorelin acetate is also available as a 1-month (3.75 mg) and 3-month (11.25 mg) formulation and is supplied in a vial as a powder, which requires suspension in a diluent (provided in a syringe), before subcutaneous or intramuscular injection via a fresh needle. The needle size is 23-gauge (subcutaneous) or 21-gauge (intramuscular) for the 3.75 mg injection and 23-gauge (subcutaneous) for the 11.25 mg injection.14
Previously, a randomised, nonblinded, crossover trial suggested that patients with prostate cancer experienced less pain with and preferred the smaller needle used to administer leuprorelin acetate compared with the larger needle used to administer goserelin acetate.15 However, our clinical impression has been that patients experience little difference in the pain from injection of the two drugs when they are unaware of needle size. Therefore, a single-blind study was carried out to investigate if there is any difference in the pain experienced by patients from injection of the LH-RH analogues goserelin acetate and leuprorelin acetate when they are unaware of the needle size used to administer study treatment. The speeds of preparation and delivery of the two injection systems were also compared
Methods
Patients with prostate cancer requiring hormonal manipulation for cytoreduction prior to primary therapy of curative intent or for the management of metastatic disease were recruited. Informed consent was obtained and ethical permission was granted by the North West Surrey Ethics Committee. Patients received either goserelin acetate or leuprorelin acetate according to the preference of their general practitioner. Patients were excluded if they had previously received LH-RH analogues or were unable to provide consent.
Patients were 'blindfolded' prior to opening of the injection pack to prevent them from seeing the syringe and needle to be used to administer their treatment. The LH-RH analogues were administered via subcutaneous injection into the anterior abdominal wall, using a standardised technique. One group received two 3.6-mg goserelin acetate injections (4 weeks apart) with a 16-gauge needle, and the other group received two 3.75-mg leuprorelin acetate injections (4 weeks apart) using a 23-gauge needle.
Following each injection, patients were asked to record the pain of injection on a visual analogue scale (VAS) ranging from 0 mm (no discomfort) to 100 mm (maximum discomfort). Speed of administration for each injection was recorded as the time taken from opening the packet to applying a small plaster to the site of injection. Patients were also asked to record the incidence of any bruising at 48 h.
Where data were normally distributed, a t-test was used to evaluate any treatment effects. If data were not normally distributed, Wilcoxon and FPRIVATE "TYPE=PICT;ALT=chi"2 tests were used. Any differences in results were considered significant if the P-value was <0.05.>
Results
Baseline patientdemographics are presented in Table 1. A total of 50 patients entered the study: 24 received goserelin acetate and 26 received leuprorelin acetate. The two treatment groups were similar in age, prostate-specific antigen level at study entry and disease stage.
Individual VAS pain scores at first and second injections are plotted in Figure 1. For the first injection, the median (range) VAS pain scores were 5 (0–38) mm and 3 (0–30) mm for goserelin acetate and leuprorelin acetate, respectively (P=0.162). For the second injection, the median (range) VAS pain scores were 7 (0–51) mm and 2.5 (0–21) mm for goserelin acetate and leuprorelin acetate, respectively (P=0.064).
The majority of patients in both groups reported minimal pain, with a VAS pain score <10 p="0.0001)," p="0.0001)," href="http://www.blogger.com/l%20fig2">Figure 2).
Comment
The results of this study indicate that there is no significant difference between the pain levels experienced by patients with prostate cancer from injections of goserelin acetate and leuprorelin acetate. Approximately two-thirds of patients experienced minimal pain and any apparent difference in the median values between the groups is unlikely to be clinically relevant.16
It has previously been suggested that patients tolerate the administration method of leuprorelin acetate better than that of goserelin acetate.15 Williams et al15 performed a 2-arm crossover study of the two drug formulations, which involved 50 patients and demonstrated a statistically significant difference between the groups in favour of leuprorelin acetate. However, the differences may not have been clinically relevant; mean VAS discomfort scores for both treatments were at the lower end of the scale and all values were classed as mild immediately after injection. Furthermore, patients did not appear to be blinded and there were conflicting descriptions of the type of patients recruited into the study and the exact routes of drug administration. In the study described here, patients were unaware of the needle size and no significant difference was seen in VAS pain scores between goserelin acetate and leuprorelin acetate. An indirect comparison of the two studies supports the concept that patients who see the needle prior to injection may have preconceptions about pain.
Goserelin acetate is available in a ready-to-use syringe and requires no mixing or further preparation prior to use.13 By comparison, leuprorelin acetate is provided as a powder in an injection vial and requires mixing with a diluent (supplied in a syringe) before use.14 In the current study, the mean time to administration for goserelin acetate was about half that observed with leuprorelin acetate, which may provide a potential time saving within clinical practice. Our findings support those of another study,17 which demonstrated that delivery of the depot injection system, used to administer goserelin acetate, took approximately half as long as delivery of the powder/diluent injection system, used to administer leuprorelin acetate.
Conclusions
Results from this single-blind study suggest that when patients are unaware of needle size the level of pain experienced following injections of goserelin acetate or leuprorelin acetate is minimal and not significantly different between the two groups. Furthermore, delivery of the goserelin acetate depot injection was quicker than that of leuprorelin acetate, providing a saving in time in a busy clinical setting.
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