Safety and efficacy of everolimus (EVE) plus exemestane (EXE) in postmenopausal women with locally advanced or metastatic breast cancer: final results from EVEREXES

Background

This study was conducted to collect clinical safety, tolerability, and efficacy data with the use of everolimus (EVE) combined with exemestane (EXE) in patients with advanced breast cancer (ABC).

Methods

The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE?+?EXE in patients with HR+, HER2???ABC in Asia and other emerging growth countries. Postmenopausal women with HR+, HER2???ABC who had documented recurrence or progression, following a nonsteroidal aromatase inhibitor therapy, were treated with EVE (10 mg/day)?+?EXE (25 mg/day) orally.

Results

A total of 235 patients received?≥?1 dose of study medication. At the end of the study, all patients ceased the treatment. Disease progression (66.0%) was the primary reason of discontinuation. The most common AEs (≥?20%) were stomatitis, decreased appetite, hyperglycemia, rash, aspartate aminotransferase increased, anemia, alanine aminotransferase increased, cough, and fatigue. No new safety concerns were identified in the current study. Median progression-free survival (PFS) in the Asian subset was similar to that of the overall population (9.3 months in both groups). Confirmed overall response rate (ORR) was achieved for 19.6% of the patients. Efficacy of EVE?+?EXE across subgroups (prior CT, line of treatment, and presence of visceral metastases) was maintained.

Conclusion

The safety and efficacy results from EVEREXES trial are consistent to data previously reported in BOLERO-2. These results support that EVE?+?EXE could be a viable treatment option for the postmenopausal women with HR+, HER2???ABC in Asian region.

     

Effects of melatonin and zinc on lipid profile and renal function in type 2 diabetic patients poorly controlled with metformin

Glycemic control and prevention of secondary complications are the most important goals of using pharmacologic treatment of diabetes mellitus (DM). The inadequate responses to oral hypoglycemic agents may be attributed to inadequate postreceptor events even when insulin levels are quite sufficient, and associated with oxidative stress induced by long-term hyperglycemia. The administration of antioxidants such as melatonin and zinc may improve tissue responses to insulin and increase the efficacy of drugs, e.g. metformin, which act through this pathway. This project was designed to evaluate the effects of melatonin and zinc on the lipid profile and renal function in type 2 DM patients poorly controlled with metformin. A placebo-controlled, double-blind clinical trial was performed in which 46 type 2 diabetic patients were selected and allocated into three groups. These groups were treated with single daily oral doses of both 10 mg of melatonin and 50 mg of zinc acetate alone: 10 mg of melatonin and 50 mg of zinc acetate in addition to the regularly used metformin or placebo, given at bedtime for 90 days. Fasting lipid profiles and microalbuminuria (MAU) were measured before initiating the treatments (zero time) and after 30 and 90 days of treatment. Daily administration of melatonin and zinc improved the impaired lipid profile and decreased the level of MAU; the addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent. In conclusion, the combination of melatonin and zinc acetate, when used alone or in combination with metformin, improves DM-related complications such as the impaired lipid profile and MAU in type 2 DM patients.     

Giant Botryoid Fibroepithelial Polyp of Bladder with Myofibroblastic Stroma and Cystitis Cystica et Glandularis

A 3-year-old boy presented with a single episode of gross hematuria and no history of previous urinary tract disorder. Imaging studies revealed a large complex polypoid filling defect in the bladder lumen. Several attempts at transurethral biopsy and cytological examination of the urine revealed clumps of benign epithelial cells, but suspicion of a malignant neoplasm such as rhabdomyosarcoma remained high and the lesion was resected. The specimen measured 15 cm, had a narrow zone of attachment to the bladder mucosa, and was grossly botryoid. Changes typical of cystitis cystica et glandularis were present at and near all surfaces. Myxoid stroma contained scattered benign fibroblasts, myofibroblasts, and smooth muscle cells. Inexplicably, one of two karyotyped stromal cells demonstrated a translocation usually associated with rhabdomyosarcoma. This child is well without evidence of bladder abnormality 1.5 years after surgery.