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【Background of Prostate Cancer】
Prostate cancer (PCa) is the most common malignant tumor in the male genitourinary system. According to the data released by the Tumor Registry Office of the National Cancer Center1, the incidence of PCa in mainland China in 2016 was 11.05 per 100,000 and the mortality rate was 4.75 per 100,000. In addition, according to the World Health Organization's International Agency for Research on Cancer (IARC), the incidence of PCa in China will be as high as 18.6 per 100,000 in 2022, with more than 134,000 new cases and more than 48,000 deaths.
The injection site of goserelin extended-release implants cannot be ignored
Androgen deprivation therapy (ADT) is the cornerstone of a variety of combination regimens throughout the patient's systematic treatment2. Gonadotropin-releasing hormone (GnRH) agonists, as the most common ADT treatment, require long-term use, hence the need to develop extended-release dosage forms; At present, there are two main dosage forms: sustained-release implants and microspheres. Among them, goserelin extended-release implant has long-term efficacy and safety follow-up data in China, and evidence-based medical evidence runs through the whole process of PCa treatment. However, the injection site-related adverse effects associated with this extended-release implantable dosage form cannot be ignored. Goserelin extended-release implant is clearly stated in the domestic instructions3,4: this product will cause injury to the injection site, and there have been reports of injury to the injection site after the use of this product, including pain, hematoma, bleeding and vascular injury events, so it is necessary to monitor the patient's signs or abdominal bleeding symptoms. Patients with a low body mass index (BMI) and/or receiving full-dose anticoagulant medication should be given extra caution when administering this product.
For PCa patients who need lifelong medical castration therapy, the injection site problems such as pain, hematoma, and bleeding caused by extended-release implants seriously affect the injection experience of patients. The 2024 edition of the "Chinese Expert Consensus on the Follow-up Management of Prostate Cancer Drug Castration Therapy" clearly points out 5: Prostate cancer should pay attention to the improvement of patients' quality of life while prolonging the survival of patients as much as possible. The adverse effects of GnRH agonists and the discomfort caused by long-term injection are important factors affecting the quality of life of patients, which may lead to reduced patient compliance and thus affect the prognosis of patients.
Improve pain at the injection site of goserelin extended-release implants
Two studies from Japan6,7 found that a significant number of patients with PCa in clinical practice will experience a certain degree of pain after subcutaneous injection into the anterior abdominal wall of the goserelin extended-release implant, which needs to be paid attention to and managed by clinicians.
Ice applied to the skin to significantly reduce pain at the injection site caused by the extended-release implant, such as the mean visual analogue score (VAS) score in the ice group was significantly lower than that in the non-ice group (25.6 mm vs 45.3 mm, P<0.001). The results of the study suggest that ice on the skin can be considered to reduce pain at the injection site of Gosserin extended-release implants. In addition, Asian patients are more sensitive to the perception of pain at the injection site. It is suggested that Chinese clinicians should also pay attention to the pain problem of patients' injection sites.
Scroll up to learn more about both studies
Part 1
Research Objectives
A study6 was conducted at Kansai Medical University in Japan to evaluate whether applying ice to the skin could reduce pain at the injection site caused by the extended-release goserelin implant.
Research Methods:
Forty-eight patients with PCa had previously been treated with goserelin extended-release implant injection (10.8 mg), and the first injection was routine without intervention, and the nurse inserted two-thirds of the needle into the subcutaneous tissue in the direction of 30°. The second time is to apply a cooling agent to the skin of the abdomen for 30 seconds and then inject it (the patient wraps the cooling agent in gauze and applies it to the injection site). Pain was assessed using a VAS score after each injection (0 mm for no pain and 100 mm for severe pain).
Findings:
The median age of the patients was 73 years, and the median number of prior doses of goserelin-extended-release implant (10.8 mg) was 4 (1-15) times. The mean VAS pain score was 32.4 mm for all patients with the first injection. The mean VAS score was significantly reduced to 16.4 mm (P=0.001) after ice application to the skin at the injection site.
Conclusions of the study
In practice, a significant number of elderly Japanese male patients feel some degree of pain. Doctors should try ice to relieve pain at the patient's injection site.
Part 2
Research Objectives
A study7 was conducted at the Daiichi Red Cross Hospital in Kyoto, Japan, to explore the optimal timing of ice packs for cryo gel packs to see if they were effective in reducing the pain of injection of goserelin extended-release implants.
Research Methods:
Pain was assessed using a VAS score (0 mm for no pain and 100 mm for severe pain). It was divided into conventional injection group and frozen gel pack ice group.
Findings:
The mean VAS score was significantly lower in the ice group than before ice (25.6 mm versus 45.3 mm, P<0.001).
Conclusions of the study
There are still a considerable number of patients in the Japanese clinic who complain of pain at the injection site caused by the goserelin extended-release implant. For patients complaining of pain at the injection site, a freezing gel pack of ice to the skin for 15 seconds may be considered to reduce pain at the injection site of the Goschelin extended-release implant.
It is expected to reduce the pain problem at the injection site of goserelin extended-release implants
The above ice compress not only reduces the pain at the injection site, but also brings a cold feeling, and the experience is not perfect; In fact, two studies in Japan have shown that some patients still complain that the ice is too cold. So, is it possible to make innovative improvements to the dosage form of goserelin extended-release implants to produce drugs with a better injection experience?
China has made a breakthrough in the preparation technology of microspheres, using the emulsification and volatilization process of solidification in water (S/O/W), and successfully developed domestic goserelin microspheres, which is expected to reduce the pain problem at the injection site of goserelin sustained-release implants. Goserelin microspheres belong to the national class 2.2 new drugs, that is, while ensuring the efficacy, reduce the adverse reactions at the injection site and improve patient compliance. In addition, a multicenter, randomized, open-label, parallel, active-drug controlled phase III confirmatory clinical trial was conducted on goserelin microspheres8.
In terms of drug efficacy, the proportion of patients with serum testosterone ≤ 50ng/dl on day 29 after the first dose was 99.3% and 100.0%, respectively. The proportion of patients who maintained castration (serum testosterone ≤50 ng/dL) on days 29-85 was 99.3% in the goserelin microsphere group and 97.8% in the goserelin extended-release implant group. The proportion of patients with a sharp rise in serum testosterone above castration levels at 72 hours of repeated dosing was 0% in the goserelin microsphere group and 1.4% in the goserelin extended-release implant group.
In terms of drug safety and tolerability, the overall safety profile of goserelin microspheres was good, and the common adverse reactions were consistent with those of similar drugs. No serious adverse events related to the trial drug occurred; The proportion of overall and ≥ grade 3 adverse events in the goserelin microsphere group was lower than that in the implant group. The incidence of adverse reactions at the injection site in the goserelin microsphere group was 0; There were no adverse events leading to discontinuation and withdrawal from the trial in the goserelin microsphere arm. In the extended-release implant group, 2.1% and 1.4% of patients reported discontinuation and withdrawal due to TEAEs, respectively.
Summary
Injection site problems such as pain, hematoma, and bleeding caused by goserelin extended-release implants seriously affect the injection experience of PCa patients, which may lead to a decrease in patient compliance and quality of life, and then affect the prognosis of patients. Two studies from Japan confirmed that ice can improve injection site pain with goserelin extended-release implants, and also highlighted that a significant number of patients still complain of injection site pain caused by goserelin extended-release implants. It is suggested that Chinese clinicians should pay attention to the demand of patients to improve their injection experience.
Goserelin Microspheres (BiotoVi) is a Class 2.2 new drug independently developed by Continental based on the innovative microsphere technology platform, with a 0 incidence of adverse reactions at the injection site and an outer diameter of only 0.8 mm from the phase III clinical study, which is expected to reduce pain at the injection site. At present, the indication of "prostate cancer patients requiring androgen castration therapy" has been officially included in the National Medical Insurance Drug List, which is expected to bring more clinical benefits to Chinese patients.
Expert Profile
Prof. Hao Liu
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
- Doctor of Medicine, Master Supervisor, Deputy Chief Physician
- He specializes in the diagnosis, surgical treatment and multidisciplinary treatment of urological tumors such as prostate cancer, bladder cancer, and kidney cancer
- EAU/AUA International Member
- Member of the compilation team of CUA's "Guidelines for the Diagnosis and Treatment of Prostate Cancer".
- He won the second prize of the Sun Yat-sen University Young Teacher Teaching Competition and the first prize of the Sun Yat-sen University Clinical Teacher Teaching Skills Competition
- 主持/参与国家自然科学基金多项，研究成果发表在European Urology、BJU International、Journal of Endourology、BMC Cancer等杂志
bibliography
1. 2022 edition of Guidelines for the Diagnosis and Treatment of Urological and Andrological Diseases in China.
2. Ann Surg,1942,115(6):1192-1200.
3. Goserelin acetate extended-release implant 3.6 mg Chinese instructions.
4. Goserelin acetate extended-release implant 10.8 mg Chinese instructions.
5. Chinese Prostate Cancer Research Collaboration Group, Chinese Expert Consensus on Follow-up Management of Prostate Cancer Drug Castration Therapy (2024 Edition), Chinese Journal of Oncology.
6. Int J Clin Oncol. 2010 Oct; 15(5):472-5.
7. Urol Int. 2014; 93(2):202-6.
8. Chin Med J (Engl). 2023 May 20; 136(10):1207-1215.
审校:Gardenia排版:Gardenia执行:Gardenia
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