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Alicante, Spain

Barnadas A.,Hospital de la Santa Creu i Sant Pau | Estevez L.G.,Centro Integral Oncologico Clara Campal | Lluch-Hernandez A.,Hospital Clinico Universitario Of Valencia | Rodriguez-Lescure A.,Hospital General de Elche | And 2 more authors.
Advances in Therapy | Year: 2011

Third-generation aromatase inhibitors (AIs) have proven to be superior to tamoxifen in terms of time to disease progression in patients with hormone receptor (HR) positive (HR+) status and, nowadays, are used in the adjuvant and neoadjuvant settings, and first-line therapy for advanced breast cancer. Letrozole is a third generation AI, as are anastrozole and exemestane. In the past, clinical studies had demonstrated that letrozole was effective as a second-line treatment of metastatic breast cancer. In this paper, pharmacokinetic and pharmacodynamic properties of letrozole are reviewed along with its activity in preclinical and clinical settings. Additionally, the results of important clinical trials such as Breast International Group (BIG) 1-98, which tested the optimal initial adjuvant endocrine treatment and the sequential therapy with letrozole and tamoxifen, MA-17 that evaluates the benefits of extended adjuvant therapy, and other important studies in advanced and neoadjuvant disease, are reviewed. Safety comparisons of treatments are also addressed. Interestingly, about 50% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers are HR+. However, HER2 positivity is a marker of antiestrogen treatment resistance. Because of this, a dual treatment is a logical approach when both receptors are overexpressed. The combination of lapatinib and letrozole leads to a significant improvement in the overall disease outcome. Also, the combination of everolimus plus letrozole has been tested in this setting. In fact, the coadministration of both agents seems to increase the efficacy of letrozole in newly-diagnosed HR+ patients. Once resistance to sequential trastuzumab and AI as monotherapy has been found, trastuzumab and letrozole combined in HR+ and HER2+ patients with advanced breast cancer can overcome resistance to both drugs administered as single agents, according to recently reported results. © Springer Healthcare 2011. Source

Illan J.,Swedish University of Agricultural Sciences | Simo M.,Hospital Universitario Of Bellvitge Ico Duran ynals | Serrano C.,Fundacion Jimenez Diaz | Castanon S.,Fundacion Jimenez Diaz | And 9 more authors.
Translational Research | Year: 2014

Dissemination of neoplastic cells into the cerebrospinal fluid (CSF) and leptomeninges is a devastating complication in patients with epithelial cell neoplasia (leptomeningeal carcinomatosis [LC]) and lymphomas (lymphomatous meningitis [LyM]). Information about the surrounding inflammatory cell populations is scarce. In this study, flow cytometry immunophenotyping was used to describe the distribution of the main leukocyte populations in the CSF of 83 patients diagnosed with neoplastic meningitis (LC, n = 65; LyM, n = 18). These data were compared with those obtained in the CSF from 55 patients diagnosed with the same groups of neoplasia without meningeal involvement (solid tumors, n = 36; high-grade lymphoma, n = 19). Median (interquartile) rates of lymphocytes, monocytes, and polymorphonuclear (PMN) cells were 59.7% (range, 35-76.6%), 24% (range, 16-53%), and 1.5% (range, 0-7.6%) in LC, respectively, and 98.5% (range, 70.8-100%), 1.5% (range, 0-29.3%), and 0% in LyM, respectively (P < 0.001). No difference was observed between patients with breast adenocarcinoma (n = 30) and lung adenocarcinoma (n = 21), nor with different rates of malignant CSF involvement. Patients with lymphoma (with or without LyM) had a similar CSF leukocyte distribution, but cancer patients with LC and without LC had a distinctive PMN cell rate (P = 0.002). These data show that CSF samples from patients with LC have a greater number of inflammatory cells and a different leukocyte distribution than seen in the CSF from patients with LyM. Description of PMN cells is a distinctive parameter of patients with LC, compared with the CSF from patients with LyM and patients with cancer but without LC. © 2014 Elsevier Inc. Source

Prado-Abril J.,Hospital Universitario Miguel Servet | Garcia-Campayo J.,University of Zaragoza | Sanchez-Reales S.,Hospital General de Elche
Revista de Psicopatologia y Psicologia Clinica | Year: 2013

There is a broad consensus that the core of psychopathology implicated in personality disorders (PDs) consists of dysfunctions related to the self and chronic and inflexible interpersonal patterns. The design of treatments for PDs requires a high degree of complexity, the use of different interventions and special attention to the therapeutic alliance. Interpersonal-cognitive therapy (ICT) is a treatment option to consider because of specific characteristics consistent with some of the dysfunctional patterns involved in PDs. Therefore, the objective of this exhaustive analysis of two cases is to confirm the efficacy of ICT. The results warrant the efficacy of ICT in achieving certain symptomatic changes, fundamental for the first sessions. Source

Alguacil J.,U.S. National Cancer Institute | Alguacil J.,University of Huelva | Kogevinas M.,Institute Municipal dInvestigacio Medica | Kogevinas M.,University of Crete | And 16 more authors.
Carcinogenesis | Year: 2011

Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolite can be rapidly hydrolyzed in acidic urine to undergo further metabolic activation and form DNA adducts in the urothelium. We conducted a large multicenter case-control study in Spain to explore the etiology of bladder cancer and evaluated the association between urine pH and bladder cancer risk, alone and in combination with cigarette smoking. In total, 712 incident urothelial cell carcinoma cases and 611 hospital controls directly measured their urine pH with dipsticks twice a day (first void in the morning and early in the evening) during four consecutive days 2 weeks after hospital discharge. We found that a consistently acidic urine pH ≤6.0 was associated with an increased risk of bladder cancer [odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.2-1.9] compared with all other subjects. Furthermore, risk estimates for smoking intensity and risk of bladder cancer among current smokers tended to be higher for those with a consistently acidic urine (OR = 8.8, 11.5 and 23.8) compared with those without (OR = 4.3, 7.7 and 5.8, respectively, for 1-19, 20-29 and 30+ cigarettes per day; Pinteraction for 30+ cigarettes per day = 0.024). These results suggest that urine pH, which is determined primarily by diet and body surface area, may be an important modifier of smoking and risk of bladder cancer. © The Author 2011. Published by Oxford University Press. All rights reserved. Source

Navarro-Sarabia F.,Hospital Universitario Virgen Macarena | Coronel P.,Tedec Meiji Farma | Collantes E.,Hospital Reina Sofia | Navarro F.J.,Hospital General de Elche | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objective: AMELIA (OsteoArthritis Modifying Effects of Long-term Intra-articular Adant) was designed to compare against placebo the effi cacy and safety of repeated injections of hyaluronic acid (HA) and its effect on disease progression over 40 months. Methods: A multicentre, randomised, patient and evaluator-blinded, controlled study in 306 patients fulfi lling American College of Rheumatology criteria for knee osteoarthritis, radiological grades II-III (Kellgren- Lawrence) and joint space width ≥2 mm. Patients received four cycles of fi ve intra-articular HA or placebo injections with a follow-up of 6 months after the fi rst and second cycles, and 1 year after the third and fourth cycles. Osteoarthritis Research Society International (OARSI) 2004 responder criteria were used to assess efficacy. The consumption of rescue medication was a secondary outcome. Adverse events were recorded for safety purposes. Results: At the 40-month visit signifi cantly more patients responded to HA compared with placebo (OARSI 2004, p=0.004). The number of responders to HA increased through the study, whereas those to placebo did not change. Signifi cant differences were also found in favour of HA for each individual component of the OARSI 2004. No safety problems were recorded. Conclusions: The results of AMELIA offer pioneer evidence that repeated cycles of intra-articular injections of HA not only improve knee osteoarthritis symptoms during the in-between cycle period but also exert a marked carry-over effect for at least 1 year after the last cycle. In this respect, it is not possible to establish if this carry-over effect refl ects true osteoarthritis remission or just a modifi cation of the disease's natural course. ClinicalTrials.gov number, NCT00669032. Source

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