New Insights into Hormonal Therapies in Uterine Sarcomas.

Uterine sarcoma (US) is a rare mesenchymal malignant cancer type, accounting for 3-7% of uterine malignancies. US prognosis is still poor due to high local and distant recurrence rates. As for molecular features, US may present variable oestrogen receptor (ER) and progesterone receptor (PR) expressions, mostly depending on histotype and grading. Surgery represents the mainstay of treatment for early-stage disease, while the role of adjuvant chemotherapy or local radiotherapy is still debated and defined on the basis of histotype, tumour grading and stage. In metastatic setting, uterine sarcomas' treatment includes palliative surgery, a metastases resection, chemotherapy, hormonal therapy and targeted therapy. As for the chemotherapy regimen used, drugs that are considered most effective are doxorubicin (combined with ifosfamide or alone), gemcitabine combined with docetaxel and, more recently, trabectedin or pazopanib. Hormonal therapies, including aromatase inhibitors (AIs), progestins and gonadotropin-releasing hormone analogues (GnRH-a) may also represent an effective option, in particular for low-grade endometrial stromal sarcoma (LGESS), due to their favourable toxicity profile and patients' compliance, while their role is still under investigation in uterine leiomyosarcoma (uLMS), high-grade endometrial stromal sarcoma (HGESS), undifferentiated uterine sarcoma (USS) and other rarer US. The present review aims to analyse the existing evidence and future perspectives on hormonal therapies in US, in order to clarify their potential role in daily clinical practice.

Doses of capecitabine and oral vinorelbine are not relevant for efficacy in breast cancer patients: an analysis of dose intensity.

BACKGROUND: The combination of capecitabine and vinorelbine is a valuable regimen in metastatic breast cancer treatment, even in pretreated patients. PATIENTS AND METHODS: Forty-one pretreated consecutive patients were treated with capecitabine, 1000 mg/m2, twice daily, for two of three weeks, and vinorelbine, given orally at a dose of 60 mg/m2, days 1 and 8 in three-week cycles. RESULTS: A total of 301 courses was given, with a median of 8 courses (range, 3-13). Median dose intensity of capecitabine was 75% of the planned dose and for vinorelbine it was 72%. We observed 18 partial response (43.9%), 15 stable disease (36.6%), and 8 progressive disease (19.5%). Median progression-free survival was 9 months (range, 1-22) and median overall survival was 27.2 months (range, 4-40). Overall response rate (complete + partial response) was not statistically different between patients who received more or less than the median dose intensity of capecitabine and vinorelbine, and there was no difference in overall survival or progression-free survival. CONCLUSIONS; Capecitabine and oral vinorelbine is an effective and well-tolerated "all-oral" regimen for advanced breast cancer patients. The use of lower doses than those currently recommended should be not detrimental in terms of efficacy.

Capecitabine and mitomycin C is an effective combination for anthracycline- and taxane-resistant metastatic breast cancer.

Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty-three patients (median age 62 years) with anthracycline- and taxane-resistant, metastatic breast cancer received mitomycin C 6 mg/m(2) on day 1, and capecitabine (Xeloda) 2,000 mg/m(2)/day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with >/=3 chemotherapy lines. A median of 6 cycles were given (range 1-19) with a complete response observed in 2 patients (3.9%), partial response in 17 (33.3%) and stable disease in 19 (37.2%). Overall response rate was 37.2% (95% CI, 24.0-50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months (1- and 2-year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/4 events were neutropenia (5.7% of patients), diarrhea (3.8%), and deep venous thrombosis (3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer.