Single-agent pegylated liposomal doxorubicin (PLD) in the treatment of metastatic breast cancer: results of an Austrian observational trial.

BACKGROUND: In advanced breast cancer, multiple sequential lines of treatments are frequently applied. Pegylated liposomal doxorubicin (PLD) has a favourable toxicity profile and can be used in first or higher lines of therapy. PLD has demonstrated response activity even after prior anthracycline exposure. METHODS: 129 consecutive patients with advanced breast cancer, of whom the majority had been massively pretreated, received PLD as monotherapy within licensed approval, for which efficacy and toxicities were documented. RESULTS: In a routine therapy setting, PLD was administered in a slightly reduced dose (median, 40 mg/m2 per cycle). Response rate (complete and partial remission) was 26%, and stable disease was observed in 19% of patients. Progression-free (PFS) and overall survival (OS) were 5.8 months and 14.2 months, respectively. There was no difference in terms of response and PFS, no matter if patients had already received anthracycline treatment. Interestingly, PFS proved similar regardless whether PLD was administered as palliative therapy in first, second or third line. Furthermore, PFS and OS were similar in patients with response or stable disease, underscoring the view that disease stabilization is associated with a profound clinical benefit. The most common side effects reported were palmar-plantar erythrodysesthesia (17%), exanthema (14%) and mucositis (12%). CONCLUSIONS: Efficacy and toxicity data in these "real life" patients permit the conclusion that PLD is a valuable option in the treatment of advanced breast cancer even in heavily pretreated patients.

Denosumab for the treatment of bone metastases in breast cancer: evidence and opinion.

INTRODUCTION: Denosumab, a fully human monoclonal antibody, targets the receptor activator of nuclear factor-kappaB (RANK) ligand, a protein essential for osteoclast differentiation, activity and survival. Loss of osteoclasts from the bone surface reduces bone turnover and bone loss in malignant and benign diseases. In breast cancer, bone metastases are frequently observed; cancer treatment-induced bone loss (CTIBL) may result as a consequence of endocrine treatment or chemotherapy. Furthermore, preclinical studies suggest a direct role of the RANK/RANK-ligand pathway in breast tumorigenesis. This paper reviews preclinical and clinical data on denosumab in breast cancer. MATERIALS AND METHODS: Studies were identified through the Medline database. Key search terms included: AMG-162, bisphosphonates, denosumab, RANK-ligand and zoledronic acid. Information available in abstract form only was retrieved from major oncology meetings, such as the American Society of Clinical Oncology (ASCO) annual meeting, ASCO breast meeting, European Cancer Organization, European Society of Medical Oncology and the San Antonio Breast Cancer Symposium. RESULTS: Denosumab was consistently well tolerated throughout clinical trials, although the observed incidence of osteonecrosis of the jaw was comparable to that with bisphosphonates. Efficacy as determined by a reduction of skeletal-related events was at least equal to zoledronic acid, and superior in one phase III study conducted in patients with metastatic breast cancer. Clinical trials investigating the role of denosumab for the prevention of CTIBL and breast cancer recurrences are currently ongoing. CONCLUSION: In conclusion, denosumab appears to be an effective and safe treatment option in patients with bone metastases from breast cancer with the potential of also preventing CTIBL.

Breast Cancer: Rank Ligand Inhibition.

Breast cancer and bone health are closely linked. Early menopause induced by gonadotropin-releasing hormone analogues or chemotherapy as well as aromatase inhibitors reduce oestrogen levels, thereby causing cancer treatment-induced bone loss (CTIBL). Furthermore, bone metastases are commonly found in advanced disease. Current treatment options for bone lesions comprise systemic anti-tumour therapy, irradiation, surgery and bisphosphonates. The main mechanism of osteolysis, osteoclast activation, is induced by the RANK ligand and suppressed by osteoprotegerin (OPG). A human antibody targeting the RANK ligand, denosumab, had superior activity compared to OPG and was therefore further developed in the clinical setting. This article reviews clinical data on denosumab. Data were obtained by searching the Medline database and abstracts from the ASCO annual meeting, ASCO breast meeting, ECCO, ESMO, and the San Antonio Breast Cancer Symposium. Clinical trials have demonstrated that denosumab reduces markers of bone turnover, and suggest equal efficacy to bisphosphonates in reducing the rate of skeletal-related events. While overall fewer side effects were observed, a numerically increased rate of osteonecrosis of the jaw was reported. Denosumab was well tolerated, and clinical activity was similar to bisphosphonates in metastatic disease. Trials of denosumab in the prevention of CTIBL are ongoing.

Preoperative chemotherapy with epidoxorubicin, docetaxel and capecitabine plus pegfilgrastim in patients with primary breast cancer.

The objective of this pilot trial was to evaluate the safety and activity profile of epidoxorubicin, docetaxel and oral capecitabine plus pegfilgrastim (TEX+P) as preoperative first-line treatment for patients with breast cancer. Eleven consecutive patients were enrolled in this prospective clinical pilot trial. Preoperative treatment consisted of epidoxorubicin [75 mg/m2 body surface area (BSA)] and docetaxel (75 mg/m2 BSA) administered sequentially on day 1 in combination with oral capecitabine 2000 mg/m2 daily divided into two doses on days 1-14 of each 3-week treatment cycle. Pegfilgrastim 6 mg fixed dose was administered s.c. on day 2 of every treatment cycle. Patients received a total of 58 cycles (median 6 cycles, range 1-6) of this therapeutic regimen. Outpatient TEX+P was well tolerated. No WHO grade IV toxicity was observed. A pathological major response to this preoperative therapy regimen could be demonstrated in eight of nine evaluable patients leading to breast-conserving surgery in seven of nine evaluable patients. We conclude that outpatient TEX+P is safe in the neoadjuvant treatment of patients with primary breast cancer. Thus, this regimen can be considered for further clinical trials.