Once-per-cycle pegfilgrastim in breast cancer patients treated with docetaxel/epidoxorubicin/cyclophosphamide.

The incidence of neutropenia following combination chemotherapy is significant in breast cancer and impairs patients' quality of life. Colony-stimulating factors significantly decrease the risk of febrile neutropenia (FN). Aim of the present study was to assess the efficacy and safety profile of once-per-cycle pegfilgrastim in reducing FN in breast cancer patients treated with docetaxel (75 mg/m(2)), epidoxorubicin (75 mg/m(2)), cyclophosphamide (500 mg/m(2)) administered every 3 weeks. Thirty-five breast cancer patients were enrolled. Chemotherapy was administered in adjuvant, neoadjuvant and metastatic setting respectively in 26, 4 and 5 patients. Toxicity was monitored with programmed clinical evaluation and blood sampling. All patients completed the therapeutic programme consisting of six cycles for overall 210 cycles. The FN appeared in 6 out of 35 patients (17%), requiring dose reduction in 3 patients. Hypertransaminasemia was registered in two patients. In one patient pegfilgrastim administration was stopped because of skin hypersensitivity reaction. In conclusion, pegfilgrastim was able to maintain doses and timing of docetaxel/epidoxorubicin/cyclophosphamide in almost all breast cancer patients treated in this series. The reduced need for daily administration of colony-stimulating factors, blood sampling, antibiotic therapy and hospitalization has a significant impact in terms of both quality of life and pharmaco-economic evaluations.

Vascular endothelial growth factor monitoring in advanced hepatocellular carcinoma patients treated with radiofrequency ablation plus octreotide: a single center experience.

Local therapies such as radiofrequency ablation (RFA) represent a valuable choice in limited hepatocellular carcinoma (HCC) and are increasingly used also in advanced tumors. Medical treatments generally gave frustrating results in advanced HCC especially if comorbidities exist. Several biologic non-chemotherapeutic drugs are currently tested in HCC and, among them, octreotide was evaluated in single series of HCC patients reporting conflicting results. We have treated a series of 35 patients affected by advanced HCC (26 M and 9 F; age range: 55-85 years, median: 73 years) with RFA followed by octreotide to primarily evaluate the safety of combined treatment and to give preliminary evaluation on its activity. We have also evaluated serum VEGF changes during the study. Child A and Child B represented 60% and about 34% of the cases, respectively. Only two patients with Child C compensated cirrhosis were included in this study. All patients have multiple liver HCC nodules and one had bone metastases. Two complete responses, 3 partial responses and 23 disease stabilization for at least three months were obtained (overall response rate, 14,2%; clinical benefit, 80%). Mean overall survival was 31.4 months. The combined treatment was well tolerated. Statistically significant correlation was found between serum VEGF and tumor progression. In conclusion, the combination of RFA and octreotide was active in advanced HCC, however, confirmation in a larger series is required.

Percutaneous ethanol injection efficacy in the treatment of large symptomatic thyroid cystic nodules: ten-year follow-up of a large series.

We present a prospective study on the long-term efficacy of percutaneous ethanol injection (PEI) treatment of a large series of symptomatic thyroid cystic nodules (STCN). Ninety-eight patients (72 females and 26 males) were treated. The mean basal volume of the STCN was 35.3 mL. In 92 of 98 patients PEI treatment induced a greater than 50% nodule shrinkage, only 6 of 92 responder patients relapsed at a follow-up of 9 years. Moreover, all the patients had a significant clinical benefit because a significant reduction of the cyst-associated symptoms was recorded. Furthermore, a limited number of sessions was required for the treatment of cysts larger than 40 mL (mean +/- standard deviation [SD]: 2.7 +/- 0.75) demonstrating the feasibility of the procedure also in the treatment of large cysts. In conclusion, PEI is an effective and inexpensive procedure with a high patient compliance and long-lasting effects in the treatment of cysts larger than 40 mL.

Percutaneous ethanol injection of autonomous thyroid nodules with a volume larger than 40 ml: three years of follow-up.

AIM: Autonomous thyroid nodules are conventionally treated by surgery or radioiodine. Percutaneous ethanol injection is a recognized alternative approach. An assessment of the long-term success and safety was conducted. MATERIALS AND METHODS: Thirty-four patients (seven men and 27 women; age range: 32-80 years; mean: 56 +/- 13 years) with an autonomous thyroid nodule (ATN) > 40 ml (volume range 41-180 ml; mean: 63.6 +/- 34.5 ml) were treated with ultrasound-guided percutaneous ethanol injection (PEI). All patients were hyperthyroid with increased radionuclide uptake in the nodule at scintigraphy. Serial serum (free T3, free T4 and thyroid-stimulating hormone (TSH)) and ultrasound studies were performed at 3, 6, 12, 18, 24 and 36 months after the first PEI session. Scintigraphy was performed before treatment and 1 month after the serum TSH became detectable or alternatively after 6 months, even if the TSH was still undetectable. RESULTS: Each patient had 1-11 sessions of PEI, with an injection of 3-14 ml of ethanol per session (total amount of ethanol per patient: 20-125 ml). Within 3 months from the end of the treatment, the recovery of extranodular uptake on isotope scan and the normalization of TSH levels were observed in 30/34 patients. A reduction (average: 62.9%) of nodule volume was recorded in all patients and only 4/34 patients were refractory to PEI. The responsiveness of ATN to PEI appeared to be dependent on the initial nodule volume (3/4 failures in patients had nodule volumes > 60 ml). Side-effects were always self-limiting. During follow-up (6-36 months) no recurrence was observed. CONCLUSION: In conclusion, the treatment of ATN > 40 ml with PEI would appear to be a valid alternative approach to traditional methods of treatment. It is safe, well tolerated and inexpensive. Its acceptability when compared with surgery and radiodioine has still to be assessed.

GTP gamma S increases thrombin-mediated inositol trisphosphate accumulation in permeabilized human endothelial cells.

Ca2+-mobilizing agonists stimulate phospholipase C-mediated phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol trisphosphate (IP3) formation in pulmonary as well as in peripheral vascular endothelial cells (EC). In general, it is believed that receptor-phospholipase C interactions involve a guanine nucleotide regulatory (G) protein. This interaction can be inhibited by Bordetella pertussis toxin in certain cells. Here we report that pertussis toxin catalyzes the [32P]ADP ribosylation of a Mr = 41,000 protein in human umbilical vein EC. However, prior EC treatment with pertussis toxin (250 ng/ml for 20 h) does not inhibit thrombin-induced Ca2+ flux or IP3 formation, despite markedly attenuating the radiolabeling of the Mr = 41,000 protein (less than 5% control). Treatment of digitonin-permeabilized human umbilical vein EC with GTP gamma S, a stable GTP analog, or AIF4-, but not with GDP beta S, stimulates IP3 accumulation. However, GDP beta S inhibits GTP gamma S-induced IP3 accumulation. Although thrombin alone is not very effective in elevating IP3 levels in permeabilized EC, thrombin and GTP gamma S act in a synergistic fashion to increase IP3 accumulation. Overall, these observations are interpreted to indicate that a pertussis toxin-insensitive G protein is a key intermediate in the signaling pathway linking thrombin receptors to phospholipase C in human umbilical vein EC.

Thrombin and histamine activate phospholipase C in human endothelial cells via a phorbol ester-sensitive pathway.

The effects of phorbol esters and synthetic diglycerides on thrombin- and histamine-stimulated increases in inositol trisphosphate (IP3) and cytosolic free calcium [( Ca2+]i) were studied in cultured human umbilical vein endothelial cells (HEC). Thrombin (0.003-3.0 U/ml) and histamine (10(-7)-10(-4) M) induced rapid increases in [Ca2+]i in suspended cells as monitored with the fluorescent calcium indicator fura-2. In [3H]myoinositol-labeled cells, both thrombin (3 U/ml)- and histamine (10(-4) M)-induced IP3 increases (195% +/- 6% and 98% +/- 4%, respectively) occurred in less than 15 sec and were temporally correlated with [Ca2+]i increases. Brief incubations (5-60 min) with different protein kinase C activators [4-beta-phorbol 12-myristate 13-acetate (1-100 nM), mezerein (100 nM), and sn-1,2 dioctanoylglycerol (0.1-10 microM)] attenuated agonist-induced increases in [Ca2+]i. These compounds also inhibited thrombin- and histamine-stimulated IP3 formation, thus suggesting a tight coupling between phospholipase C activation and calcium flux in cultured HEC. Overall, these observations suggest that the pathway linking receptors to phospholipase C stimulation in human endothelial cells is sensitive to protein kinase C activation.