Cost-effectiveness of ribociclib as initial treatment for premenopausal women with advanced breast cancer in Singapore.

BACKGROUND: CDK4/6 inhibitors have shown promising results for treating advanced breast cancer (ABC) and are routinely used in Singapore. In view of their high costs, it is important to assess their relative value compared to existing standards of care in the local setting. AIMS: This study evaluates the cost-effectiveness of adding ribociclib to goserelin and a nonsteroidal aromatase inhibitor or tamoxifen as initial therapy for premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ABC in Singapore. METHODS: A partitioned survival model with four health states (progression-free on first-line treatment, progression-free on second-line treatment, progressed disease, and death) was developed from a healthcare system perspective over a 10-year time horizon. Key clinical inputs were derived from the MONALEESA-7 trial, and survival curves were extrapolated beyond the trial period. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. A discount rate of 3% was applied to both costs and outcomes. One-way deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties. RESULTS: The base-case analysis resulted in an incremental cost-effectiveness ratio (ICER) of SGD197, 667 per quality-adjusted life-year. Sensitivity analyses showed that the ICER was sensitive to the survival parametric distribution, ribociclib price, time horizon, and utility weights used. Even when these were varied, ICERs remained high and not cost-effective in the local context. CONCLUSION: At its current price, adding ribociclib to endocrine therapy is unlikely to be cost-effective in Singapore for HR+, HER2- ABC. Results from this study are useful to inform future funding decisions for CDK4/6 inhibitors alongside other factors including clinical effectiveness, safety, and budget impact considerations.

Evaluation of goserelin effectiveness based on assessment of inflammatory cytokines and symptoms in uterine leiomyoma.

Background Uterine leiomyoma is a benign tumour of the uterine smooth muscles associated with an elevated level of inflammatory cytokines. Goserelin, a synthetic gonadotropin-releasing hormone analogue, suppresses the production of sex hormones and release of inflammatory cytokines in uterine leiomyoma cells. Objective The primary objective of this study was to find out the effectiveness of subcutaneous goserelin therapy on lowering serum levels of inflammatory cytokines and improving uterine leiomyoma-related symptoms in female patients diagnosed with uterine leiomyoma. The secondary objective was to assess the tolerability to goserelin therapy used in the management of this tumour. Setting Outpatient gynaecological clinic of the medical consultation department of Baghdad Teaching Hospital, Baghdad province, Iraq. Methods A single centre, prospective, longitudinal, cohort study was carried out on female patients diagnosed with uterine leiomyoma. Goserelin 3.6 mg subcutaneous injection was given in a consecutive monthly dose for the total time duration of three months. Serum levels of inflammatory cytokines, tumour necrosis factor-α and monocyte chemotactic protein-1 were detected before and after goserelin therapy in a consecutive monthly assessment. The study also assessed the improvement in uterine leiomyoma-related symptoms, including pelvic pain alongside the incidence of goserelin-related side effects during therapy schedules. Main Outcome Measures Assessment of serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 alongside uterine leiomyoma-related symptoms, including pelvic pain and goserelin-related side effects. Results There was a significant decrease in serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 compared to the baseline level over the 3-month duration of goserelin therapy (0.11 ± 0.02 vs. 0.74 ± 0.19) pg/mL; (0.07 ± 0.00 vs. 0.44 ± 0.18) pg/mL respectively. Patients showed a clinical improvement regarding uterine leiomyoma-related symptoms following each of the consecutive monthly doses of goserelin therapy (n = 11, 55%, P < 0.0001; n = 15, 75%, P < 0.0001; n = 18, 90%, P < 0.0001) respectively. This also includes a significant decrease in the intensity of leiomyoma-related pelvic pain before and after goserelin therapy (7.2 ± 1.43 vs. 3.05 ± 1.14, P < 0.0001). The majority of patients reported vaginal dryness (60%) as the main goserelin-related side effect. Conclusion Goserelin therapy reduces serum levels of inflammatory cytokines, tumour necrosis factor- α and monocyte chemotactic protein-1, improving leiomyoma-related symptoms with good tolerability in patients with uterine leiomyoma.

Putting patients first: an inventive service delivering cancer treatment at home.

Aim: This study evaluated the patient experience of receiving subcutaneous chemotherapy at home via a unique 'Cancer Treatment at Home' outreach service adapted by the UK Clatterbridge Cancer Centre NHS Foundation Trust. Patients & methods: The service involved using highly trained nurses to deliver cancer treatments to patients in their own homes. Patient outcomes were monitored over 12 months via the Systemic Anti-Cancer Therapy at Home (SACT) survey using handheld electronic devices. Results: Of the 56 participating cancer patients, 53 provided responses. Patients received subcutaneous trastuzumab, denosumab, pembrolizumab, fulvestrant and goserelin. Overall, 96% of respondents were 'very satisfied' and 4% 'satisfied' with the service. All respondents would recommend the service to others. Conclusion: The 'Cancer Treatment at Home' service has improved the patient experience for cancer care and has been recognized nationally for its achievements.

Assessment of ovarian function after chemotherapy in women with early and locally advanced breast cancer from Serbia.

PURPOSE: Among harmful effects of chemotherapy is the reduction of ovarian function. The aim was to determine the serum levels of FSH, LH, estradiol and AMH after chemotherapy followed by endocrine therapy in breast cancer patients. METHODS: The study included 40 premenopausal hormone receptor-positive breast cancer patients aged 33-50 years. Anthracycline-based chemotherapy received 14/40 while anthracycline-taxane combination received 26/40 of patients, followed by tamoxifen (30/40) or tamoxifen plus goserelin (10/40). All of them experienced chemotherapy-induced secondary amenorrhea. Hormone levels were determined by ELISA. Statistics included Spearman's test, Mann-Whitney test and multiple linear regression analysis. RESULTS: Undetectable AMH levels were observed in 62.5 and 33.3% of patients with time period < 2 and ≥ 2 years from completion of chemotherapy to sample collection. Median levels of hormones for patients treated with anthracycline-based compared to anthracycline-taxane therapy were: 15.5 vs. 22.3 IU/L for FSH; 10.9 vs. 13.6 IU/L for LH; 55.5 vs. 39.5 pg/mL for estradiol; 0.11 vs. 0.11 ng/mL for AMH. The multiple linear regression showed that: women who received goserelin had significantly lower FSH; those with shorter time from completion of chemotherapy to sample collection had significantly higher LH and lower estradiol; younger women had higher AMH levels. CONCLUSIONS: The ovarian function was recovered from chemotherapy-induced secondary amenorrhea with time elapsed since the completion of adjuvant chemotherapy. It may be less disrupted in patients who received anthracycline-based chemotherapy and goserelin plus tamoxifen, as well.

Cost-effectiveness analysis of LHRH agonists in the treatment of metastatic prostate cancer in Italy.

OBJECTIVES: Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with metastatic prostate cancer. We compared the cost-effectiveness of the five different 3-month formulations of LHRH agonists currently available for advanced prostate cancer in Italy, because these differ both in their capacity to suppress testosterone and in their acquisition costs. METHODS: A probabilistic, patient-level simulation model was developed to compare the cost-effectiveness, from the perspective of the Italian National Health Service (INHS), of leuprorelin 11.25 mg and 22.5 mg, triptorelin 11.25 mg, buserelin 9.9 mg, and goserelin 10.8 mg. The model incorporated testosterone-dependent progression-free and cancer-specific survival functions, LHRH agonist effectiveness data, and national costs and tariffs. Cox's proportional hazard models were used to compute total and progression-free survival functions based on clinical data from 129 patients with metastatic prostate cancer treated in an Italian center. Bayesian random effects models were employed to summarize evidence from published literature on testosterone suppression obtained with the available LHRH agonists. RESULTS: Estimated total survival was ≈5 years, with a maximum difference between treatment options of ≈2 months. There was a mean difference of almost €2,500 in lifetime total costs between the least costly option (leuprorelin 22.5 mg) and the most expensive (goserelin). In the incremental cost-effectiveness analysis, leuprorelin 22.5 mg dominated all alternatives except buserelin, which had an incremental cost-effectiveness ratio versus leuprorelin 22.5 mg of ≈€12,000 per life-month gained. CONCLUSIONS: Based on modelling with meta-analysis of comparative survival data, leuprorelin 22.5 mg was the most cost-effective treatment of the available depot formulation LHRH agonists.

[Assessment of goserelin treatment in adjuvant therapy for premenopausal patients with breast cancer in Japan-zoladex breast cancer study group trial-B].

OBJECTIVE: Goserelin (GOS) therapy in an adjuvant setting for estrogen receptor(ER)-positive premenopausal patients with breast cancer was assessed in a randomised comparative study. METHODS: ER positive premenopausal patients with n + or n 0 and T > or = 3 cm received tamoxifen (TAM) 20 mg/day, GOS 3.6 mg/4 weeks or GOS + TAM for 2 years, and the clinical efficacy and safety of these regimens were assessed. RESULTS: In the data analysis of total 207 patients, hazard ratios of disease free survival (DFS) and overall survival (OS) in the GOS group compared to the TAM group were 0.87 and 2.10,respectively. The incidence of adverse drug reactions was similar (42-55%) in all three groups. Since the number of patients in this study did not reach the target number, the efficacy could not be assessed from a statistical aspect. Therefore,meta-analysis with similar foreign studies(ZIPP) was implemented. The results of meta-analysis showed that the hazard ratios of DFS and OS in the GOS group compared to the non-GOS group were 0.83 and 0.85, respectively. CONCLUSION: Although the analysis of 207 patients did not show any statistically significant difference between each of the treatment groups, the results of meta-analysis showed a significant prolongation of DFS in the GOS group. Also high tolerability of GOS was suggested. From these results, GOS was considered highly useful in adjuvant therapy for ER-positive premenopausal patients with breast cancer.

Injection systems for two luteinising hormone-releasing hormone agonists: a comparative assessment of administration times and nurses' perceptions.

The aim of this study was to compare the speed of administration (preparation and delivery) and nurses' perceived ease of use and relative safety of two injection systems used to administer luteinising hormone-releasing hormone agonists: a depot system used to administer goserelin acetate ('Zoladex', AstraZeneca) and a vial system used to administer leuprorelin acetate ('Prostap', Wyeth). This was a randomised, crossover study with 82 volunteer nurses (50 pre-registration and 32 post-registration). All nurses were timed in the administration of both systems and all were required to assess the two systems by completing a questionnaire. Results indicate that both pre- and post-registration nurses administered the depot system in less time than the vial system. Overall mean times for administration of the depot system and the vial system were 1.70 and 3.34min, respectively. In questionnaire responses, significantly more nurses thought that the depot system had 'good safety precautions' compared with the vial system (85% versus 40%; P<0.001) and significantly more nurses also expressed a preference for the depot system (58% versus 42%; P=0.036). In conclusion, this study demonstrates that nurses prefer the one-step depot system used to administer goserelin acetate over the vial system used to administer leuprorelin acetate.

Assessment of ovarian failure and osteoporosis in premenopausal breast cancer survivors.

UNLABELLED: Premenopausal women who develop ovarian failure after receiving chemotherapy are at a higher risk of rapid bone loss. Pharmacists have successfully implemented osteoporosis screening programmes in the general population and thus, assessment of breast cancer survivors for ovarian failure and osteopenia could represent a novel focus for oncology pharmacists. Therefore, we conducted a retrospective chart review to determine the adequacy of ovarian failure and osteoporosis assessment and management in premenopausal breast cancer survivors. METHODS AND RESULTS: The charts of 20 women diagnosed with early stage breast cancer treated with cyclophosphamide over a 4.5-year timespan were included. Their median age was 36.7 years (range 29.8-41). The median cyclophosphamide cumulative dose was 9 g/m(2) (range 2.4-14.45), with a median duration of follow-up being 4.62 years. The assessment of ovarian failure mainly occurred by documenting menstrual periods, which has been questioned as a reliable method for assessing ovarian failure. Menses stopped while or shortly after receiving chemotherapy in 11 women. Prior to and during cyclophosphamide administration, osteoporosis screening or counselling was not documented for any patient. After completion of chemotherapy administration, eight patients were counselled regarding osteoporosis and seven women were screened for osteoporosis with a dual X-ray absorptimetry (DXA) scan. Five women had DXA scans indicative of osteopenia according to World Health Organization guidelines. CONCLUSIONS: Improvements are needed in the documentation and potentially also the management of ovarian failure and osteoporosis in premenopausal breast cancer survivors receiving cyclophosphamide-based regimens. This represents a potential opportunity for pharmacists to manage long-term chemotherapy toxicity.

Coping and health-related quality of life in men with prostate cancer randomly assigned to hormonal medication or close monitoring.

Prostatic carcinoma and its treatment have been associated with adverse effects on health-related quality of life (HRQoL). Individual differences in appraisal and coping have been suggested to mediate these HRQoL outcomes. A randomized trial of 65 men with non-localized prostate cancer compared several treatments and tested associations between appraisal, coping, and HRQoL. These patients, and 16 community volunteers matched for age and general health, undertook psychosocial assessments before treatment and after 6 months of treatment. Compared with baseline assessments, men on hormonal treatments reported impaired sexual function. Groups did not differ on emotional distress, existential satisfaction, subjective cognitive function, physical symptoms, or social and role functioning. For individuals, hormonal treatments were more frequently associated with decreased sexual, social and role functioning, but were also associated with improved physical symptoms. In hierarchical regression analysis, HRQoL was lower for men who had more comorbid illnesses, a history of neurological dysfunction, higher threat appraisals, or higher use of coping strategies at baseline. These results showed that pharmacological hormonal ablation for prostate cancer can improve or decrease HRQoL in different domains. HRQoL in men with prostate cancer was associated more strongly with appraisal and coping than with medical variables.

[Hysteroscopic ablation of the endometrium in cases of dysfunctional uterine bleeding--advantage of preparations including zoladex]. / Khisteroskopska ablatsiia na endometriuma pri disfunktsionalni matochni kruvotechniia--predimstva na podgotovkata sus Zoladeks.

Hysteroscopic endometrial ablation (HEA) is a new alternative for patients with dysfunctional uterine bleeding (DUB), resistant to medical treatment. The relatively thin endometrium is a big advantage at the time of operation. In this article the results of an initial series of hysteroscopic operations (HEA) are given--as a whole and depending on preoperative treatment with GnRH-agonist. Seventeen patients with DUB underwent HEA. Six of them were pretreated with Goserelin acetate (Zoladex 3.6 mg, Astra Zeneca) two subcutaneous application at 28 days interval. The other 11 women were operated in the early postmenstrual period without medical pretreatment. Comparison was made between the two groups regarding preoperative endometrial thickness, operative time, operative complications, duration of hospital stay, change of the menstrual pattern after 6 and 12 months. Results showed 41.2% achievement of persistent amenorrhoea in patients as a whole (62.7% in the Zoladex group and 27.2% in the untreated group). Better results in the patients with Zoladex pretreatment (shorter operative time, higher incidence of amenorrhoea, patient's higher evaluation of the operation) can be explained with the reduced endometrial thickness at the time procedure. The authors consider the hysteroscopic roller-ball endometrial ablation as an upto-date cost-effective method for treatment of DUB. The method is quick, with very low incidence of complications, easy toleration, immediately recovery of the patient and the only possibility for women with high anaesthesiologic and operative risk. Two depot-doses of Zoladex before hysteroscopy lead to better intra- and postoperative results.

Hysteroscopic endometrial destruction, optimum method for preoperative endometrial preparation: a prospective, randomized, multicenter evaluation.

OBJECTIVE: To compare the outcome and cost-effectiveness of various forms of preoperative endometrial preparation prior to hysteroscopic endometrial destruction for abnormal uterine bleeding. METHODS: This was a multicenter, prospective, comparative, randomized study conducted in a tertiary care hospital in Cairo, Egypt and 2 academic tertiary care teaching hospitals in the United States. One hundred thirty-one premenopausal women, who had completed childbearing, mean age of 45.7 years, with abnormal uterine bleeding refractory to medical management without histologic evidence of endometrial neoplasia were studied. The 131 patients were randomized for preoperative preparation for hysteroscopic endometrial destruction into 1 of 5 groups as follows: Group I, dilation and curettage (D & C) (39); Group II, gonadotropin-releasing hormone analogue (GnRHa) for 1 month (23); Group III, GnRHa for 3 months (26); Group IV, danazol for 3 months (26); and Group V, medroxyprogesterone acetate (MPA) 15 mg for 3 months (27). The choice of endometrial ablation or endometrial resection was left to the surgeon. RESULTS: Improvement in bleeding patterns, amenorrhea, operative times, complications, and relative cost were the measured outcomes. The mean follow-up time was 1 year from the time of the procedure. Overall, in Group I, 39/39 (100%) improved and 7/39 (18.0%) experienced amenorrhea; in Group II, 21/23 (91.3%) improved and 9/23 (39.1%) experienced amenorrhea; in Group III, 24/26 (92.3%) improved and 10/26 (38.5%) experienced amenorrhea; in Group IV, 24/26 (92.3%) improved and 9/26 (34.6%) experienced amenorrhea; and in Group V, 23/27 (85.1%) improved and 7/27 (25.9%) experienced amenorrhea. CONCLUSION: Endometrial destruction whether by the ablation or resection technique, regardless of the type of surgical pretreatment is a safe and effective surgical approach for treating abnormal uterine bleeding. D & C or MPA appear to be the most cost-effective pretreatment regimens. MPA pretreatment may confer the added advantage of decreasing blood flow and allowing better hysteroscopic visualization than D & C pretreatment.

Assessment of the effect of ovarian suppressants on women with the premenstrual syndrome: iterative spectral analysis.

The daily mood symptoms of four women with the premenstrual syndrome (PMS) were recorded before, and after spontaneous or induced ovarian failure. Response was assessed by iterative spectral analysis and the results compared with techniques based on changes in the mean or median mood score, or the measurement of premenstrual tension in arbitrary 'menstrual' cycles. Only iterative spectral analysis had the capacity to establish the significance of a change in symptom cyclicity, an important attribute for a condition such as the PMS.