Analysis of plasma cytokines and angiogenic factors in patients with pretreated urothelial cancer receiving Pazopanib: the role of circulating interleukin-8 to enhance the prognostic accuracy.

BACKGROUND: Pazopanib achieved the end point of clinical activity in pretreated patients with urothelial cancer in a single-group, phase 2 trial. The objective was to identify biological predictors of clinical benefit to pazopanib in these patients. METHODS: EDTA blood samples were collected at baseline (T0) and after 4 weeks (T1) of treatment, together with radiological imaging in all 41 patients to analyse plasma circulating angiogenic factor levels by multiplex ELISA plates. Changes from T0 to T1 in marker levels were matched with response with the covariance analysis. Univariable and multivariable analyses evaluated the association with overall survival (OS), adjusted for prespecified clinical variables. Net reclassification improvement (NRI) tested the performance of the recognised Cox model. RESULTS: Increasing IL8(T1) level associated with lower response probability at covariance analysis (P=0.010). Both IL8(T0) (P=0.019) and IL8(T1) (P=0.004) associated with OS and the prognostic model, including clinical variables and IL8(T1) best-predicted OS after backward selection. The NRI for this model was 39%.When analysed as a time-varying covariate, IL8(T1) level<80 pg ml(-1) portended significantly greater response (∼80%) and 6-month OS (∼60%) probability than level ≥ 80. CONCLUSION: IL8-level changes during pazopanib allowed for a prognostic improvement and were associated with response probability.

Mitoxantrone as first-salvage chemotherapy in relapsed breast cancer.

Mitoxantrone was administered at the dose of 14 mg/m2 i.v. every 3 weeks to 25 consecutive women with measurable progressive disease who relapsed after adjuvant CMF and endocrine therapy. The treatment plan consisted in the delivery of 6 cycles, unless disease progression or severe toxicity occurred. All patients were evaluable for drug response and toxicity. One patient achieved complete remission and 6 partial remission, for a total response rate of 28%. Objective tumor response was observed in all major sites of disease. The median time to achieve remission was 3 months. The median duration of response was 7 months (range, 5-39+), and the median survival for the entire group was 10 months (range, 3-39+). Results were influenced only by the duration of disease-free status from the end of adjuvant CMF chemotherapy. In fact, all tumor responses were documented in woman with free intervals exceeding 1 year (7 of 17 or 41%). Treatment was generally well tolerated, with 10 patients developing leukopenia at some time during treatment. Only 2 patients received less than 75% of the projected dose because of granulocytopenia. Complete alopecia occurred in only 2 cases. Three patients developed a fall greater than 15% in left ventricular ejection fraction, but no episode of congestive heart failure was observed. We conclude that mitoxantrone is an effective and safe drug which can be utilized in women relapsing after adjuvant CMF.

The effects of an energy stimulator on blood electrolyte and lactate levels in athletes under training.

The effects of a mineral-vitamin-sugar preparation has been tested on a group of volley ball players under training. Plasma electrolytes (Na, K, Cl), erythrocyte electrolyte content, plasma lactate concentration and erythrocyte water content have been determined before and after a training session in three different experimental situations: a) controls; b) acute treatment with the energy stimulator; c) chronic treatment (8 days) with a similar preparation of the energy stimulator. The results are indicative of a significantly lower lactate production and a more stable electrolyte concentration after treatment with respect to the control data.