Manuel González Barón

Classification of anticancer drugs--a new system based on therapeutic targets.

The arrival of a great number of new antineoplastic agents has made it necessary to reclassify all of them. Anticancer drugs may act at different levels: cancer cells, endothelium, extracellular matrix, the immune system or host cells. The tumour cell can be targeted at the DNA, RNA or protein level. Most classical chemotherapeutic agents interact with tumour DNA, whereas monoclonal antibodies and small molecules are directed against proteins. The endothelium and extracellular matrix may be affected also by specific antibodies and small molecules.

Gemcitabine plus vinorelbine in nonsmall cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin

Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20–30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed.

Nutrition and pharyngeal cancer: Results from a case-control study in Spain

Oropharyngeal and hypopharyngeal cancer is increasing all over the world, frequently affecting more and more women and younger individuals and not only the typical 50‐ to 60‐year‐old heavy smoker and drinking man. In addition, 5‐year overall survival rate remains poor (30% to 40% in most series), despite advances in treatment. Therefore, it is crucial to understand as accurately as possible the risk factors for these malignancies to improve primary prevention.

Renal tolerance to cisplatin in patients 70 years and older.

The purpose of this study was to evaluate cisplatin nephrotoxicity in patients 70 years and older and to identify factors influencing nephrotoxicity occurrence. Forty-nine (N = 49) patients older than 70 years were studied retrospectively. All patients received treatment with cisplatin. Variables under study were as follows: prechemotherapy serum creatinine levels (Crb), maximum serum creatinine level during treatment (Crmax), steady serum creatinine level 3 months after treatment completion (Crstb), as well as their corresponding creatinine clearance values (CrbC, CrmaxC, CrstbC) as calculated by the Cockroft and Gault formula. Maximum creatinine increment (Imax = Crmax − Crb), stable creatinine increment (Istb = Crstb − Crb) and the corresponding clearance decrements (Dmax and Dstb) were calculated as well. The potential relationship of the above variables to cisplatin dose intensity and accumulated dose as well as to different prognostic factors were also considered. Assessment of associated conditions was carried out by means of Charlson comorbidity index. The patients’ mean age was 73 years (range: 70–79 years). There were 43 men (88%) and 6 women (12%). Mean cisplatin dose intensity was 27 mg/m2/wk. A total of 157 chemotherapy courses were administered with a mean of 3.2 per patient. Mean Crb was 1.02 mg/dl (95% CI = 1.02–1.12), mean Crmax was 1.45 (95% CI = 1.34–1.46), and mean Crstb was 1.24 (95% CI = 1.16–1.32). Imax was equal to 0 in 13 patients (26%) and more than 0.4 mg/dl in 21 patients (43%). Istb was equal to 0 or negative in 22 (45%) and more than 0.4 in only 9 patients (18.3%). No significant relationship of serum creatinine levels, creatinine clearance levels, or of their increments or decrements to cisplatin dose intensity or accumulated dose were found. These levels also did not correlate with age, sex, comorbidity or Eastern Cooperative Oncology Group score. In 85% of patients, Crmax was reached between chemotherapy initiation and the third chemotherapy course, and thereafter renal function began to recover despite continued administration of cisplatin. Cisplatin is well tolerated by patients 70 years and older and dose intensity does not seem to influence renal function deterioration. Therefore, we failed to find reasons to encourage modification or limitation of cisplatin treatment in the elderly population.

Role of anti-Her-2 therapy in bladder carcinoma

Bladder cancer, in its advanced stage, has very few therapeutic strategies with proven efficacy. Platinum-combination chemotherapy can be considered a standard for first-line therapy, but after progression there is no standard therapy, and the prognosis is very poor. The development of targeted therapies in the last few years has significantly changed the prognosis of a wide variety of tumors. In bladder cancer, there is no targeted therapy currently approved for its use in advanced disease. There is evidence that Her-2 amplification and/or overexpression is seen in bladder cancer, and may influence prognosis. Anti-Her-2 drugs, such as trastuzumab or lapatinib, are under investigation in urothelial neoplasms, but there is no phase III trial that has evaluated their use in bladder cancer. We review the published evidence about Her-2 determination, its influence on bladder carcinoma prognosis, the clinical development of anti-Her-2-targeted therapies, and the possible future research directions involving this pathway in bladder cancer.

An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

BackgroundGene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse.MethodsWe included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models.ResultsAn 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database.ConclusionsThis study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.

A phase II trial of cisplatin and vinorelbine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck

We assessed the response rate and the toxicity of cisplatin plus vinorelbine in patients with this condition.

Factores etiológicos del cáncer de pulmón: fumador activo, fumador pasivo, carcinógenos medioambientales y factores genéticos

Cada ano se diagnostican en Espana 18.000 nuevos casos de cancer de pulmon (CP). Aproximadamente el 80-90% de los casos se relacionan con el consumo de tabaco. El humo del tabaco contiene mas de 300 sustancias quimicas, de las que mas de 40 son potenciales carcinogenos. En la ultima decada, tanto en Espana como en Europa, se ha observado una preocupante tendencia al aumento de la prevalencia de mujeres fumadoras. El abandono del habito tabaquico reduce sustancialmente el riesgo de desarrollar un CP, que, no obstante, no iguala al de los individuos que nunca han fumado. Por otra parte, la exposicion ambiental al tabaco tambien ha demostrado ser causa de un aumento del riesgo de desarrollar CP. Este trabajo ofrece una revision actualizada sobre los principales factores etiologicos del CP, el riesgo asociado al consumo de tabaco y a su exposicion ambiental, los factores geneticos asociados y la exposicion medioambiental a sustancias como el arsenico, el asbesto o los hidrocarburos aromaticos policiclicos.Every year, in Spain 18,000 new cases of lung cancer (LC) are diagnosed. Approximately, 80-90% LC in men and women are directly attributable to tobacco abuse. Cigarette smoke contains over 300 chemicals, 40 of which are known to be potent carcinogens. In the last decade, as in Spain, prevalence of smoking in women has generally increased in the European Union. LC risk can be substantially reduced after smoking cessation, yet never reaches baseline. On the other hand, environmental tobacco smoke exposure (passive smoking) in nonsmokers appears to have a significantly increased risk of LC. An updated of etiology factors of LC, risk related to duration as well as intensity of smoking, relationship between environmental tobacco smoke exposure and LC risk, genetic predisposition and a variety of occupational and environmental exposures implicated as potential risk factors for the development of LC will be reviewed here.

Comparison of prognostic gene profiles using qRT-PCR in paraffin samples: a retrospective study in patients with early breast cancer.

Introduction Gene profiling may improve prognostic accuracy in patients with early breast cancer, but this technology is not widely available. We used commercial assays for qRT-PCR to assess the performance of the gene profiles included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Ratio. Methods 153 patients with early breast cancer and a minimum follow-up of 5 years were included. All tumours were positive for hormonal receptors and 38% had positive lymph nodes; 64% of patients received adjuvant chemotherapy. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) specimens using a specific kit. qRT-PCR amplifications were performed with TaqMan Gene Expression Assays products. We applied the three gene-expression-based models to our patient cohort to compare the predictions derived from these gene sets. Results After a median follow-up of 91 months, 22% of patients relapsed. The distant metastasis-free survival (DMFS) at 5 years was calculated for each profile. For the 70-Gene Signature, DMFS was 95% -good prognosis- versus 66% -poor prognosis. In the case of the Recurrence Score, DMFS was 98%, 81% and 69% for low, intermediate and high-risk groups, respectively. Finally, for the Two-Gene Ratio, DMFS was 86% versus 70%. The 70-Gene Signature and the Recurrence Score were highly informative in identifying patients with distant metastasis, even in multivariate analysis. Conclusion Commercially available assays for qRT-PCR can be used to assess the prognostic utility of previously published gene expression profiles in FFPE material from patients with early breast cancer. Our results, with the use of a different platform and with different material, confirm the robustness of the 70-Gene Signature and represent an independent test for the Recurrence Score, using different primer/probe sets.

UFT® Modulated with Leucovorin in Advanced Colorectal Cancer: Oncopaz Experience

A phase II trial of UFT (Tegafur and Uracil) modulated by leucovorin was undertaken by the Oncopaz Cooperative Group to assess the efficacy and toxicity of this combination in patients with advanced colorectal cancer. A total of 75 patients were given 500 mg/m2 intravenous leucovorin and 195 mg/m2 of oral UFT on day 1, followed by oral leucovorin 15 mg/12 h and 195 mg/m2/12 h of oral UFT on days 2-14. An overall response rate of 39% was obtained, with seven complete responses (9%), and 22 partial responses (29%). The primary toxicity was gastrointestinal, with grade 1-2 diarrhea occurring in 8.5% of courses, and grade 3-4 in 3.5%. Hematologic toxicity was minimal, and there were no deaths due to toxicity. This regimen was active and well tolerated in patients with advanced colorectal cancer, including those 70 years of age or older.