A Study of Angiogenesis Markers in Patients with Renal Cell Carcinoma Undergoing Therapy with Sunitinib.

BACKGROUND: Sunitinib is a tyrosine kinase inhibitor (TKI) targeting tumour angiogenesis in patients with advanced renal cell carcinoma (RCC). Currently no universally agreed model exists correlating the expression of angiogenesis markers with the success of treatment. PATIENTS AND METHODS: We retrospectively analysed archival tissue for 59 RCC patients treated with sunitinib. The expression of angiogenesis markers VEGF-A, VEGFR, PDGFßß, PDGFR, CCND1 and CA9 was assessed by immunohistochemistry (IHC) and correlated with overall survival (OS) and progression-free survival (PFS). RESULTS: The median OS and median PFS of the whole group of patients was 24.6 months (17.3-34.2) and 19.5 months (11-27) respectively. VEGFA was positive in 29% of tumors, whereas VEGFR was expressed in only 12% of tumours. PDGFßß and its receptor were detected in a minority of cases. CCND1 and CA9 were positive in 44% and 60% of cases. CONCLUSION: The OS and PFS achieved by our patients reflected previous observations seen with sunitinib, but no correlation was found between expression of angiogenesis markers and clinical outcome.

Drug waste minimization as an effective strategy of cost-containment in oncology.

BACKGROUND: Sustainability of cancer care is a crucial issue for health care systems worldwide, even more during a time of economic recession. Low-cost measures are highly desirable to contain and reduce expenditures without impairing the quality of care. In this paper we aim to demonstrate the efficacy of drug waste minimization in reducing drug-related costs and its importance as a structural measure in health care management. METHODS: We first recorded intravenous cancer drugs prescription and amount of drug waste at the Oncology Department of Udine, Italy. Than we developed and applied a protocol for drug waste minimization based on per-pathology/per-drug scheduling of chemotherapies and pre-planned rounding of dosages. RESULTS: Before the protocol, drug wastage accounted for 8,3% of the Department annual drug expenditure. Over 70% of these costs were attributable to six drugs (cetuximab, docetaxel, gemcitabine, oxaliplatin, pemetrexed and trastuzumab) that we named 'hot drugs'. Since the protocol introduction, we observed a 45% reduction in the drug waste expenditure. This benefit was confirmed in the following years and drug waste minimazion was able to limit the impact of new pricely drugs on the Department expenditures. CONCLUSIONS: Facing current budgetary constraints, the application of a drug waste minimization model is effective in drug cost containment and may produce durable benefits.

Sarcomatoid renal cell carcinoma: clinical outcome and survival after treatment with sunitinib.

BACKGROUND: Renal tumors with sarcomatoid changes are aggressive malignancies with poor prognosis. Immunotherapy and chemotherapy have provided little benefit. The efficacy of treatments targeting the vascular endothelial growth factor pathway is unclear because of the lack of clinical trial data and the small number of published series. PATIENTS AND METHODS: We reviewed the clinical records of 23 consecutive patients with advanced sarcomatoid renal cell carcinoma who were treated with sunitinib in our center. Overall survival (OS), progression-free survival, and response rate were evaluated. We also studied the effect on clinical outcome of performance status, prognostic risk group, and proportion of sarcomatoid component. RESULTS: Median OS was 15.7 months (95% confidence interval [CI], 5.0-21.2). Median progression-free survival was 5.7 months (95% CI, 3.2-12.6). Seven patients (30%) had an objective response, 5 patients (22%) had stable disease, and 11 (48%) had progressive disease. The median survival of the 13 (56.5%) patients with performance status of 0 to 1 was 20.9 months (95% CI, 9.7-63.3) whereas the medial survival of the 10 (43.5%) patients with performance status of 2 to 3 was 5.0 months (95% CI, 1.1-16.5). Objective responses were observed only among the 13 (56.5%) patients with performance status of 0 to 1. Heng prognostic risk group and percentage of sarcomatoid component did not influence outcome. CONCLUSION: Sunitinib shows efficacy in advanced renal tumors with sarcomatoid differentiation particularly in patients with good performance status. Appropriate patient selection and risk-directed treatment remains essential in this aggressive disease.

Exploratory predictive and prognostic factors in advanced breast cancer treated with metronomic chemotherapy.

The aim of the present study is to evaluate the clinical and biological factors (including markers of angiogenesis) as potential predictors of prognosis and benefit from metronomic therapy in patients with advanced breast cancer (ABC). Recent data suggest antiangiogenic activity of metronomic therapy. The study population included 62 patients with pretreated ABC who received cyclophosphamide and methotrexate orally. Tumour samples were analysed by immunohistochemistry for HER2, Ki-67, thymidine phosphorylase (TP), vascular endothelial growth factor and vascular endothelial growth factor receptor. The results from immunohistochemical analysis and clinico-pathological variables were studied to test their potential association with benefit from metronomic therapy. The median overall survival, progression-free survival and survival postprogression were 7.1 (range 0.2-38.3), 2.6 (range 0.2-28.9) and 3 (range 0-34.2) months, respectively. Among the clinical variables, age, performance status and previous therapy with taxanes were significantly associated with outcomes. Among the molecular markers, TP was found to be associated with progression-free survival. Metronomic therapy is an effective choice for ABC. Young women with a more indolent disease had the greatest benefit from this treatment. TP tumour expression might aid decision making but these findings must be confirmed in larger prospective, properly designed studies.

First-line chemotherapy with or without biologic agents for metastatic breast cancer.

Breast cancer (BC) is one of the most important causes of morbidity and mortality representing the first tumor in the female sex in terms of incidence and the third in terms of mortality in the western world. An increased survival is evident in metastatic breast cancer (MBC) as a result of the introduction of novel therapeutic agents. Oncologists have several options available (chemotherapy, hormone-therapy and biologic agents such as anti-angiogenic and anti-HER2 drugs) and the challenge nowadays is the individualization of the therapy (tailored approach). Despite better diagnostic tools and new therapeutic agents, at the present the main treatment goal in MBC is still palliation. Into the attempt to better tailor treatments, the search for predictive factors deserves a huge effort. This review faces the different approaches in terms of first-line chemotherapy for MBC together with the biological therapies recently approved for the treatment of this tumor.