Drug plasma levels, metabolism data and clinical results were evaluated after the daily administration of either 500 or 1,000 mg aminoglutethimide (AG, Orimeten, Ciba-Geigy) plus hydrocortisone acetate (20 mg b. i. d.). A total of 34 patients with advanced breast cancer entered the study: 17 were given 1,000 mg/day and 17 received 500 mg/day for at least 3 months. A novel HPLC method was developed to determine the levels of AG and its known metabolites [N-acetyl-AG (NAG), formyl-AG, nitroglutethimide, hydroxy-AG] in the biological samples. AG plasma concentration was significantly higher during the 1,000-mg/day regimen. NAG was the only metabolite observed in plasma, always occurring at concentrations lower than those of the parent drug. The ratios between NAG and AG levels distinguish two statistically different groups of patients. Irrespective of the dose, a partial response was observed in 44% of the patients; no change in 32% of cases; and progressive disease had an incidence of 24%. The probability of response was not dependent on the drug AUC or on the NAG/AG ratio and did not significantly depend on previous hormone treatment. Neither the plasmatic level of the AG or metabolite concentrations nor the NAG/AG ratio seemed to affect the incidence of side effects.

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In an attempt to define the activity and toxicity of low-dose aminoglutethimide plus steroid replacement in advanced breast cancer, we treated 40 patients with aminoglutethimide 500 mg/day + hydrocortisone 50 mg/day. Previous treatment consisted of additive hormones in 29 patients, oophorectomy in 8, and chemotherapy in 32. Among the 37 patients evaluable for response and toxicity, 5 objective responses (16.2%) and 20 stable diseases (54%) were noted. Toxicity, absent in 23 patients (62.1%) and mild in 14, consisted mainly of Grade I (WHO) nausea, drowsiness, cutaneous rash, and dizziness. Responders and patients with stable disease experienced a similar survival (median not reached at 22 months). Aminoglutethimide at low doses appears to be beneficial in patients refractory to conventional therapies even if the objective response rate is low.

PurposeRadiodermatitis is likely to be an inevitable side effect of radiotherapy (RT) but experiencing pain relief during RT might contribute making treatment more acceptable and less impairing. The current study aimed to assess the subjective perceptions and experiences of skin toxicity in a sample of women undergoing adjuvant RT for breast cancer.MethodsEighty patients were randomly assigned to one out of two groups: treatment (i.e., a newly developed topical product) and control (i.e., standard-of-care). Patients underwent adjuvant RT for 3 weeks. Clinical assessment of radiodermatitis and self-reported levels of pain, relief, and perceptions of treatment response were collected at the initiation of RT (T1), during RT (T2 and T3), and 2 weeks after treatment completion (T4). To assess changes in skin-related QoL, a subgroup of patients completed the Padua Skin-Related QoL questionnaire at T0 (before the initiation of RT) and at T4.ResultsA comparable timing of onset and severity of radiodermatitis during treatment was observed in both groups. The treatment group reported lower levels of pain and higher levels of relief compared to the control group when skin toxicity was at its highest levels (T2 and T3). Independent of the group, levels of perceived improvements in clinical status increased over time, whereas skin-related QoL worsened from T0 to T4.ConclusionCurrent findings outline the relevance of integrating clinical evaluations of radiodermatitis with patients’ subjective experiences of skin toxicity in interventional studies. Moreover, they provide preliminary evidence about the soothing effect of a newly developed topical product, thus supporting its usefulness of as a supportive care.