Subclinical coronary atherosclerosis, detected by computer tomography with coronary calcium score, and the occurrence of major cardiovascular events at 5 years of follow-up in a cohort of patients with systemic sclerosis.

BACKGROUND: Spreading data describe cardiovascular disease (CVD) as a growing cause of hospitalization in systemic sclerosis (SSc) patients. Although interstitial lung disease and pulmonary arterial hypertension (PAH) remain the principal causes of mortality, the presence of CVD has been shown to further increase mortality in SSc patients. Few and contrasting data are available on cardiovascular impairment, particularly of subclinical coronary arteries disease, in SSc patients. The aims of this study were: 1) to determine the demographic, clinical, and cardiovascular differences between the groups of SSc patients with and without subclinical coronary atherosclerosis (SCA) assessed by coronary calcium score; 2) to verify the performance of cardiovascular risk scores in SSc for detection of SCA major cardiovascular events (MCVE); 3) to evaluate the risk factors associated to MCVE in 5 years of follow-up in this study group of patients. METHODS: Sixty-seven SSc patients were enrolled in this study. SCA was assessed using quantification of coronary calcium score by computerized tomography, reported as Agatson. Evaluation of common cardiovascular risk scores, carotid plaques by Doppler ultrasonography, the history of peripheral artery disease (PAD), lipid profiles, and clinical and laboratiristic characteristics of SSc were assessed at baseline visits for each patient. Factors associated with the presence of SCA were assessed by multivariate logistic analysis. A five years prospective study was performed for the evaluation of MCVE occurrence and its possible predictors. RESULTS: The prevalence of SCA was 42% (Agatston scores of 266.04 ± 455.9 units) in our group of SSc patients. Patients with SCA were principally older (p = 0.0001) and had higher rates of CENP-B antibodies (57% vs 26%; p = 0.009), pulmonary arterial hypertension (PAH) (25% vs 3%; p = 0.008), dysphagia (86% vs 61%; p = 0.027), and users of statins (36% vs 8%; p = 0.004), carotid plaque (82% vs 13%; p = 0.0001), PAD (79% vs 18%; p = 0.0001), and metabolic syndrome (25% vs 0%; p = 0.002) than patients without SCA. Metabolic syndrome (OR: 8.2, p = 0.0001), presence of a PAD (OR: 5.98, p = 0.031), and carotid plaque (OR: 5.49, p = 0.010) were the main factors associated with SCA in SSc patients, by multivariate regression analysis. MCVE occurred in 7 patients. By multivariate COX regression analysis unique predictor of MCVE in 5 years of follow-up in our SSc patients was the presence of PAH (HR: 10.33, p = 0.009). Of note, the contemporary presence of PAH and SCA (defined as "not pure" pattern of PAH) was observed in 71% of patients with the occurrence of MCVE CONCLUSION: This study evidenced the high presence of the new "not pure" pattern of PAH, which could worsen the outcome in SSc in a medium-term (5 years) observation period. Furthermore, our data confirmed a higher cardiovascular impairment in SSc due to the presence of both SCA, mainly associated with typical cardiovascular risk factors, and PAH, life-threatening complications of SSc, that is the principal cause of the occurrence of MCVE in our SSc patients. A careful assessment of cardiovascular involvement in SSc and a more aggressive therapeutic strategy for preventing CAD and treating PAH should be highly suggested to reduce MCVE in SSc patients.

Capecitabine: indications and future perspectives in the treatment of metastatic colorectal and breast cancer.

Fluoropyrimidines remain the most important drugs in the treatment of breast and colorectal carcinoma, but response rates and survival time have been disappointing. Optimal administration is by continuous intravenous infusion, which makes it cumbersome to use and compromises patient independence. Recently, a number of new agents, including fluorouracil prodrugs and selective dihydropyrimidine dehydrogenase inhibitors, have been studied, with promising results. Capecitabine is the first in a new class of fluoropyrimidines. It is an oral, tumor-activated anticancer drug whose activity mimics that of continuously infused 5-fluorouracil. Capecitabine circumvents dihydropyrimidine dehydrogenase catabolism and appears to be at least as active against metastatic colorectal and breast cancer as conventionally administered intravenous 5-fluorouracil, with significantly less toxicity, an improved quality of life, and lesser cost. Capecitabine may ultimately provide enhanced antitumor activity to fluorouracil-containing regimes for advanced colorectal and breast cancer.

New chemoradiotherapy combinations in head and neck cancer.

Head and neck squamous cell cancer is the sixth most common cancer worldwide. Surgical management is effective as a single modality only for early-stage cancers (30% of patients). Making progress in this cancer is of vital interest. The standard treatment for advanced disease is chemoradiotherapy, with the goal of palliation of symptoms and prolongation of life. Response rates to even the best of regimens are approximately 30-40%, with the median survival period of approximately 6 months. Various approaches to treatment of recurrent disease are under investigation, including new drugs or combinations of drugs, with radiotherapy.

Fluoropyrimidines in the treatment of advanced neoplastic diseases: role and advantages of UFT.

The fluoropyrimidine antimetabolites were employed in a wide range of neoplastic diseases. In particular, 5-fluorouracil in association with other chemotherapeutic agents, or biochemical modulators was successfully used in the treatment of colorectal, gastric, breast, head and neck cancers. With this type of chemotherapy, a response rate < or = 20% was obtained in gastrointestinal tumors, without a statistically significant impact on the overall survival. UFT is a combination of tegafur an uracil, which has the important advantage of an improved oral bioavailability, if we compare it with 5-fluorouracil. Uracil, avoiding the fluoropyrimidine degradation inside the tumor cells, increases the permanence of the metabolically active fluoropyrimidine into the target cell, so having an improvement in the therapeutic activity. A very large spectrum of cancers were treated with this molecule. In particular, a response rate in the range of 20-40% was observed in the treatment of patients with metastatic colorectal cancer. Phase III trials are ongoing to evaluate the advantage on 5-FU of this new fluoropyrimidine in terms of clinical efficacy, and quality of life, considering the possibility to administer it orally.