Everolimus plus exemestane in hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: incidence and time course of adverse events in the phase IIIb BALLET population.

BACKGROUND: The addition of everolimus to exemestane therapy significantly improves progression-free survival in postmenopausal patients with hormone-receptor (HR)-positive HER2-negative endocrine-resistant breast cancer. However, the safety profile of this schedule still might be optimized. METHODS: Patients included in the BALLET trial were assessed. The objectives of this analysis were to provide additional information on the safety profile of this schedule depending on prior anticancer therapies and to characterize the time course of adverse events (AEs) and serious AEs (SAEs) of clinical interest throughout the study period. Non-infectious pneumonitis (NIP), stomatitis, asthenia and weight loss were selected as AEs of clinical interest. RESULTS: The safety population of this analysis comprised 2131 patients. There were similar incidences of AEs and SAEs of clinical interest regardless of previous anticancer therapies. Most stomatitis and asthenia events occurred within the first three months. Incidence of weight loss appeared to plateau except in the case of grade 3-4 events, which occurred rarely. The incidence of any grade NIP (between 2 to 6%) and grade 3-4 NIP (between 0 to 1%) was low across the study, but steady. CONCLUSIONS: Everolimus plus exemestane is a well-known therapeutic option for aromatase inhibitor pretreated advanced breast cancer patients, and its toxicity profile is similar to that described in previous studies. Close monitoring, especially within the first three months, early intervention with preventive measures and patient education to help recognize the first signs and symptoms of AEs, will help to reduce their incidence and severity.

Intravenous ferrous sucrose versus placebo in addition to oral iron therapy for the treatment of severe postpartum anaemia: a randomised controlled trial.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of intravenous iron versus placebo added to standard oral iron therapy in the treatment of severe postpartum anaemia. DESIGN: A randomised, double-blind, parallel-group, placebo-controlled clinical trial was performed in a single centre. SETTING: Hospital Clinic of Barcelona, Barcelona, Spain. POPULATION: A cohort of 72 women with severe postpartum anaemia (6.0-8.0 g/dl) treated with oral ferrous sulphate (two tablets of 525 mg). METHODS: Women were randomised to receive either intravenous ferrous sucrose (200 mg/24 hours for two consecutive days) or intravenous placebo, in addition to standard iron therapy. Clinical and laboratory data were obtained at 1, 2, and 6 weeks. MAIN OUTCOME MEASURES: Haemoglobin and haematocrit at 1, 2, and 6 weeks. Other haematological and clinical parameters, psychological status, and adverse side effects were also evaluated. RESULTS: Haemoglobin and haematocrit values were comparable in women receiving intravenous iron or placebo in addition to oral iron therapy at any of the time points. At 6 weeks, haemoglobin level (mean ± SD) was 12.2 ± 1.0 versus 12.2 ± 0.9 g/dl, with a mean difference of -0.03 (95% CI -0.6 to 0.6), in the placebo and in the intravenous iron groups, respectively. No differences were found between clinical symptoms of anaemia, psychological status, and adverse side effects between groups. CONCLUSIONS: Intravenous iron added to oral iron therapy did not show significant benefits over placebo, neither in haemoglobin rise nor in symptoms or adverse side effects.

Long-term effect of hormone therapy on bone in early menopause: vertebral fractures after 20 years.

OBJECTIVE: The role of menopausal hormone therapy (HT) on vertebral fracture prevention after treatment discontinuation is controversial. The aim of this study was to assess the incidence of vertebral fracture in a group of women who received HT in early menopause compared with another group who did not receive such treatment after 20 years of follow-up. SUBJECTS AND METHODS: In 1990, we included 177 patients aged 43-57 years old (mean 49.1 ± 3.9 years) in a prospective study to evaluate the effect of different HT regimens on bone metabolism and mineral density. After 20-21 years, a total of 49 patients from the initial study were retrieved. These patients were divided into two groups: the first group included women who had taken HT, and those who constituted the control groups and had not taken HT formed the second group. Clinical and demographic data were analyzed and vertebral fracture was assessed by radiology using the Genant semiquantitative scale. RESULTS: Of the 49 patients enrolled, 32 (65.3%) received HT for an average of 5.5 (± 2.96) years while the 17 (34.7%) remaining belonged to the control group without treatment. A higher rate of vertebral fracture was observed in the group receiving HT (p = 0.03). Depending on the degree of fracture (Genant semiquantitative method), subsequent analysis by subgroups corroborated the higher rate in the group receiving HT in all cases (p < 0.05). Multivariate analysis ruled out the effect of the clinical and demographic variables (current age, age at menopause, body mass index, type of menopause and drugs for the treatment of osteoporosis) in the final result. CONCLUSION: In spite of the fact that this study does not have a large enough sample, our data suggest that HT used in the early years of menopause does not present a long-term protective effect on vertebral fracture after discontinuing treatment.