GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial.

BACKGROUND: Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women's health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI. PATIENTS AND METHODS: This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI. RESULTS: A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups. CONCLUSION: This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.

A randomised trial of secondary prophylaxis using granulocyte colony-stimulating factor ('SPROG' trial) for maintaining dose intensity of standard adjuvant chemotherapy for breast cancer by the Anglo-Celtic Cooperative Group and NCRN.

BACKGROUND: Guidelines on the use of haematopoietic colony-stimulating factors for patients having adjuvant chemotherapy for breast cancer are designed to minimise the risk of neutropaenic infection (Smith TJ, Khatcheressian J, Lyman GH et al. Update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 3: 187-205; Aapro MS, Bohlius J, Cameron DA et al. Effect of primary prophylactic G-CSF use on systemic therapy administration for elderly breast cancer patients. Breast Cancer Res Treat 2011; 47: 8-32; Carlson RW, Allred DC, Anderson BO et al. Breast cancer. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 2009; 7: 122-192). Non-randomised data suggest that the achievement of planned dose intensity (DI) may have an important effect on survival. This trial compared the effects of granulocyte colony-stimulating factor, GCSF, against standard management following a first neutropaenic event (NE) in achieving planned DI. PATIENTS AND METHODS: Adult patients receiving adjuvant or neoadjuvant chemotherapy were randomised following a first NE, defined as hospitalisation due to neutropaenic fever, an absolute neutrophil count (ANC) ≤1.5 × 10(9)/l requiring treatment delay or dose reduction of 15% or more of planned dose. The study was initially planned to enrol 816 patients to detect a difference of 10%. This was difficult to achieve in the timeframe and the trial size was amended. Thus, 407 patients were randomly assigned to filgrastim for 7 days or pegfilgrastim versus standard care. The amended study was designed to have 80% power to detect an absolute difference of 14% of planned DI between the two groups. RESULTS: Most regimens were anthracycline-based many of which included a sequential taxane and/or were in clinical trials. Around 82.7% had an NE in the first three cycles. A total of 401 had calculable relative dose intensity (RDI) data. A target of 85% planned RDI was achieved in only 50% of patients in the control arm compared with 75% in the GCSF arm (P < 0.0001). A secondary end point revealed a reduction in post-randomisation NEs, 65.7% controls versus 18.2% with GCSF. CONCLUSIONS: Secondary intervention with GCSF showed a statistically significant improvement in the achievement of adequate RDI in non-intensive regimens. This may have important clinical implications for outcome.

Development and validation of the Stirling Eating Disorder Scales.

The development and reliability/validity check of an 80-item, 8-scale measure for use with eating disorder patients is presented. The Stirling Eating Disorder Scales (SEDS) assess anorexic dietary behavior, anorexic dietary cognitions, bulimic dietary behavior, bulimic dietary cognitions, high perceived external control, low assertiveness, low self-esteem, and self-directed hostility. The SEDS were administered to 82 eating disorder patients and 85 controls. Results indicate that the SEDS are acceptable in terms of internal consistency, reliability, group validity, and concurrent validity.

Comparison of eating disorders and other dietary/weight groups on measures of perceived control, assertiveness, self-esteem, and self-directed hostility.

Anorexic and bulimic patients were compared to obese dieters, nonobese dieters, and normal controls on measures of perceived control, assertiveness, self-esteem, self-directed hostility, and psychiatric caseness. The anorexic and bulimic groups both scored significantly differently in the expected direction from the other three groups on all measures. There were no significant differences between the anorexic and bulimic groups and in turn, no significant differences among the obese, nonobese dieters, and normal controls. Results are in keeping with the notion that perceived control, low assertiveness, low self-esteem, and self-directed hostility are characteristics of eating disorder patients that differentiate them from individuals who display dietary/weight features, as well as from normal controls.

Scottish psychiatrists in primary health-care settings. A silent majority.

There has been a growing number of reports of psychiatrists moving out into primary-care settings. We report a survey of consultant psychiatrists to assess the extent of this practice in Scotland. Some time spent in the primary-care setting was reported by 56%, the figures being highest in rural areas. An equal number of non-consultant medical staff were involved. Most schemes were initiated by psychiatrists, over half of whom had had some postgraduate general-practice experience. A similar survey in England and Wales showed that only 19% of consultant psychiatrists spent time in primary-care settings, a smaller proportion of non-consultant staff being involved. The value of working in primary-care settings has yet to be assessed.

Anorexia and bulimia in anorexia nervosa: a study of psychosocial functioning and associated psychiatric symptomatology.

Seventeen fasting patients with anorexia nervosa and 15 who also binged were compared in terms of their psychosocial functioning and associated psychiatric symptomatology, using the Delusions Symptoms and States Inventory (Foulds & Bedford, 1975). Both groups scored very highly on the state of anxiety, depression, and elation sets of the DSSI, but less highly on the compulsive and ruminative symptoms sets and on the phobic dissociative and conversion symptom sets. The bingeing anorexic group was significantly older and heavier than the fasting group and experienced more feelings of self-harm and guilt. The bingeing group reported sexual interference during childhood, and currently experienced a desire to vomit during sexual activity to a significantly greater degree than the fasting group.