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Treatment of a relapsed glioma is a clinical challenge nowadays. New active treatments are required to treat these difficult diseases. Here we present a durable complete remission of a relapsed glioblastoma that has achieved a complete radiologic response with the combination of cetuximab and bevacizumab, in a third-line setting, that has offered a progression-free survival of 20 months. We consider here both potential mechanisms for the explanation of this result. First, the potential target of the cancer stem cells (CSCs) with these two antibodies, and second, the potential recruitment of the immune system to directly pursue the CSCs.

Thyroid cancer is the endocrine tumor that bears the highest incidence with 33 550 new cases per year. It bears an excellent prognosis with a mortality of 1530 patients per year (Jemal et al.; 2007). We have been treating patients with thyroid carcinoma during many years without many innovations. Recently, we have assisted to the development of new agents for the treatment of this disease with unexpected good results. Here we present a review with the old and new methods for the treatment of this disease.

Treatment of anaemia is a very important aspect in the management of cancer patients. In order to carry out a consensus process about the use of erythropoietic stimulating agents (ESAs) in cancer patients, the Spanish Society of Medical Oncology (SEOM) elaborated a working group which coordinated a panel of medical oncology specialists. This working group has reviewed the main issues about the use of ESAs. In addition a consensus meeting was held in Madrid on 25 April 2007. The following conclusions were made: Since ESA treatment increases the haemoglobin (Hb) level and decreases the red blood cell (RBC) transfusion requirements, ESAs should be used within the approved indications in patients undergoing chemotherapy treatment, beginning at a Hb level below 11 g/dl and maintaining it around 12 g/dl, with iron supplements if necessary. Neither increasing the ESA dose in non-responders nor the use of ESAs in the treatment of chronic cancer-related anaemia is recommended.

Resumen Las neoplasias de ovario suelen presentarse en estadios avanzados. La citorreduccion primaria completa continua teniendo una importancia clara en el pronostico de las pacientes. Hemos asistido a una progresiva mejoria en el resultado de los tratamientos, desde la aparicion de los taxanos, asi como de la importancia de la via intraperitoneal. Sin embargo, esta ultima no acaba de imponerse como practica clinica habitual dadas las dificultades que presenta. Tras el final de la quimioterapia adyuvante, la mayoria de las pacientes presentara una recaida. La identificacion de las pacientes con mayor riesgo puede permitir el establecimiento de una pauta terapeutica que mejore las perspectivas de este subgrupo de pacientes. La enfermedad residual tras citorreduccion primaria y quimioterapia adyuvante tiene una importancia pronostica y su manejo no responde a pautas estandarizadas.

The aim of this study was to analyze prognostic variables associated with long-term survival in patients with stage III non-small-cell lung cancer enrolled in a Spanish Lung Cancer Group (SLCG) phase II trial.Between May 2001 and June 2006, 139 patients were enrolled. The initial design included 3 arms: sequential chemotherapy (CT) followed by standard thoracic radiation therapy (TRT; RT), concomitant CT/TRT followed by consolidation CT, or induction CT followed by CT/TRT. Based on the results of the Radiation Therapy Oncology Group 9410 trial, the sequential arm was closed. Induction or consolidation therapy comprised docetaxel plus gemcitabine. Concomitant treatment comprised docetaxel plus carboplatin plus 60 Gy TRT. A univariate and a Cox proportional hazard regression analysis of the following 11 variables were performed: age, sex, Eastern Cooperative Oncology Group performance status (PS), histology, forced expiratory volume in 1 second, disease stage, nodal status, hemoglobin level, completion of RT treatment, completion of induction or consolidation plus concomitant treatment, and RT delay.With a median follow-up of 23 months for living patients, median survival was 13.07 months for the consolidation arm and 14.65 months for the induction arm. The 4-year survival rates were 25.37% and 32.35%, respectively. Only RT treatment completion (P.0001) and induction or consolidation plus concomitant treatment completion (P.0001) were associated with longer survival.Based on this retrospective analysis of patients enrolled in the SLCG 0008 randomized phase II study, age, sex, PS, and clinical parameters are not good predictors of overall survival; however, completion of treatment is needed to achieve long-term results.

Metastatic prostate cancer is an incurable disease. After a period of hormone sensitivity that allows for the use of antiandrogens, the disease invariably progresses to a situation of androgen-independent growth, which deserves the consideration or the use of chemotherapy. As many of these patients are elderly and fragile, treatment with chemotherapy is challenging. Therefore, new drugs are required. Preclinical evidence supports the role of estrogen receptor (ER) signaling in prostate cancer. In this paper, we report the first published evidence of PSA control in a patient with metastatic prostate cancer treated with fulvestrant acetate.

Breast cancer is the most common type of cancer among women, and clinicians have long recognized its heterogeneity. Its detection and treatment in early stages allow for reduction of mortality. Despite the advances and new strategies for combining surgical, radiotherapy, and chemotherapy options, however, the percentage of patients developing metastases and advanced stages remains high. Even though serum tumor markers have been used for the early diagnosis of metastases, their systematic determination has not had an effect on survival. Methods that are more reliable are needed to detect metastases earlier than with the common clinical methods and thus start treatment before overt relapse. Early indicators of response or resistance to treatment are also an issue in clinical practice. Imaging techniques are time consuming, and it is difficult to detect changes that indicate response limited to therapy, and approaches to defining changes in tumor mass are time and resource consuming. In contrast, detection of circulating tumor cells (CTC) could be a useful tool in early detection of relapse and response to systemic chemotherapy. Extremely sensitive techniques are available that are easily applied to peripheral blood samples, which might provide enormous research possibilities in this area.

Lung cancer is a major health problem due to its incidence and mortality. The risk factors, the existence of a preclinical phase, and the relationship between stage at diagnosis and survival are known. A number of strategies that aim to diagnose lung cancer in its earliest stages, based principally on imaging studies, are therefore being tested. Several drugs aimed at reducing the probability of developing lung cancer in the at-risk population are also under study. At the present time, the results obtained have not been encouraging and we do not have a clear strategy either for early diagnosis or for the use of chemopreventive agents.

Purpose Although current treatment options for metastatic non–small-cell lung cancer (NSCLC) rely on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response. Patients and Methods From August 2001 to October 2005, 444 stage IV NSCLC patients were enrolled. RNA was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Patients were randomly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment. Patients in the control arm received docetaxel plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received docetaxel plus cisplatin, and those with high levels received docetaxel plus gemcitabine. The primary end point was the overall objective response rate. Results Of 444 patients enrolled, 78 (17.6%) went off study before receiving one cycle of chemotherapy, mainly due to insufficient tumor tissue for ERCC1 mRNA assessment. Of the remaining 346 patients assessable for response, objective response was attained by 53 patients (39.3%) in the control arm and 107 patients (50.7%) in the genotypic arm (P = .02). Conclusion Assessment of ERCC1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel and cisplatin. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to refine a multibiomarker profile predictive of patient outcome.

Objective The aim of this study was to analyze the risk factors on the perinatal transmission of hepatitis C virus (HCV). Study design A retrospective cohort study with 711 infants born to 710 HCV-infected mothers was conducted at the Hospital La Fe, in Valencia, Spain, from 1986 to 2011. As potential risk factors for transmission we analyzed: maternal age, mode of acquisition of HCV infection, HIV co-infection, antiretroviral treatment against HIV, CD4 cell count, HIV and HCV viral load, liver enzyme levels during pregnancy, smoking habit, gestational age, intrapartum invasive procedures, length of rupture of membranes, length of labor, mode of delivery, episiotomy, birth weight, newborn gender and type of feeding. Results Overall perinatal HCV transmission rate was 2.4%. The significant risk factors related with HCV transmission were maternal virus load >615 copies/mL (OR 9.3 [95% CI 1.11–78.72]), intrapartum invasive procedures (OR 10.1 [95% CI 2.6–39.02]) and episiotomy (OR 4.2 [95% CI 1.2–14.16]). HIV co-infection and newborn female were near significance ( p = 0.081 and 0.075, respectively). Conclusions Invasive procedures as fetal scalp blood sampling or internal electrode and episiotomy increase vertical transmission of HCV, especially in patients with positive HCV RNA virus load at delivery.

Resume Cette revue souligne les nombreuses decouvertes en biologie moleculaire dans le cancer bronchique ayant un impact therapeutique potentiel aussi bien dans un proche que dans un lointain avenir. De nombreuses donnees precliniques et cliniques montrent que le taux d’ARNm de BRCA1 est un modulateur differentiel de la sensibilite a la chimiotherapie. De faibles taux sont predictifs d’une sensibilite au cisplatine et d’une resistance aux agents anti-microtubules et l’inverse est observe pour des taux eleves. Une grande partie des travaux recents a porte sur les mutations et l’amplification du gene EGFR (epidermal growth facor receptor). Ces mutations sont predictives de reponse aux inhibiteurs tyrosine-kinase de EGFR chez les patients porteurs d’adenocarcinomes bronchiques metastases, avec augmentation par trois du temps jusqu’a progression et de la survie pour les patients recevant ce type de molecules. Des preuves s’accumulent quant a l’interaction des voies de signalisation d’EGFR et des œstrogenes, incitant a programmer des essais cliniques associant inhibiteurs tyrosine-kinase d’EGFR et anti-aromatases. La comprehension de l’importance de ces decouvertes peut aider a modifier la pratique clinique en cancerologie en adaptant les chimiotherapies et/ou les biotherapies ciblees, et permettant ainsi d’ameliorer aussi bien la survie que le cout-efficacite.

Objetivo: Comparar la eficiencia del tratamiento del cancer de pulmon no microcitico avanzado (CPNMA), previamente tratado con quimioterapia, con erlotinib (ERL), docetaxel (DOC), pemetrexed (PEM) o el tratamiento de soporte habitual (BSC). Metodos: Analisis de minimizacion de costes, coste-utilidad e impacto presupuestario, mediante un modelo de Markov con tres estados: inicial, progresion de la enfermedad y muerte. Se simulo la evolucion de una cohorte de pacientes durante 2 anos (ciclos mensuales). Subpoblaciones analizadas: en segunda linea de tratamiento (caso basico), segunda y tercera lineas (ECOG de 0–1 o no) y tercera linea. Tiempos de supervivencia y sin progresion: obtenidos a partir de tres ensayos clinicos. Anos de vida ajustados por calidad (AVAC): obtenidos de un estudio en 154 pacientes. Perspectiva del Sistema Nacional de Salud (SNS) (costes directos sanitarios). Utilizacion de recursos estimada mediante un panel de oncologos espanoles y de la bibliografia. Costes unitarios: a partir de bases de datos espanolas (€ de marzo de 2006). Descuento anual: 3,5% (costes y utilidades). Analisis de sensibilidad: para las subpoblaciones; resultados a 3 anos (distribuciones Weibull y Loglogistica); y probabilistico (Monte Carlo). Resultados: A los 2 anos, se obtendrian mas AVAC por paciente con ERL (0,24) que con DOC (0,23) y BSC (0,18). No hubo diferencias frente a PEM. El coste total por paciente fue menor con ERL (17.838 €) que con DOC (20.392 €;–2.554 €) o con PEM (27.317 €;–9.479 €) y mayor que con BSC (8.198 €; + 9.640 €). ERL “domina” (es mas eficaz, con menores costes) a DOC y reduce costes en comparacion con PEM. Coste de ganar un AVAC o un ano de vida con ERL, frente a BSC: 160.667 € y 56.706 €, respectivamente. Los costes de ganar un AVAC con DOC y PEM frente a BSC fueron mayores que con ERL: 243.880 € y 318.650 €, respectivamente; asimismo, los costes por AVG fueron mayores con DOC y PEM que con ERL: 71.729 € y 112.465 €, respectivamente. Los resultados fueron estables en los analisis de sensibilidad. Si 1.000 pacientes con CPNMA fueran tratados con ERL, el ahorro anual para el SNS (tasas de sustitucion: 5%–65%) oscilaria entre 123.000–1.600.000 €, en sustitucion de DOC, y 448.000–5.831.000 €, en sustitucion de PEM. Conclusiones: Segun el modelo, el tratamiento con ERL del CPNMA previamente tratado, es mas coste-efectivo que DOC y PEM, cuya sustitucion produciria ahorros para el SNS.

Background: North American and Japanese non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activation via tyrosine kinase (TK) mutations respond dramatically to gefitinib treatment. To date, however, the frequency and effect of EGFR TK mutations have not been examined in European patients. Patients and methods: Eighty-three Spanish advanced NSCLC patients who had progressed after chemotherapy, were treated with compassionate use of gefitinib. Patients were selected on the basis of available tumor tissue. Tumor genomic DNA was retrieved from paraffin-embedded tissue obtained by laser capture microdissection. EGFR mutations in exons 19 and 21 were examined by direct sequencing. Results: EGFR mutations were found in 10 of 83 (12%) of patients. All mutations were found in adenocarcinomas, more frequently in females (P = 0.007) and non-smokers (P = 0.01). Response was observed in 60% of patients with mutations and 8.8% of patients with wild-type EGFR (P = 0.001). Time to progression for patients with mutations was 12.3 months, compared with 3.6 months for patients with wild-type EGFR (P = 0.002). Median survival was 13 months for patients with mutations and 4.9 months for those with wild-type EGFR (P = 0.02). Conclusions: EGFR TK mutational analysis is a novel predictive test for selecting lung adenocarci

Background The purpose of this study was to evaluate the tolerability and efficacy of BMS-184476, an analog of paclitaxel, in patients with advanced non-small-cell lung cancer (NSCLC) progressing or relapsing following at least one prior chemotherapy regimen. Patients and methods Fifty-six previously treated advanced NSCLC patients received BMS-184476 at a dose of 60 mg/m2 administered intravenously over 1 h every 21 days. Results The median number of cycles delivered per patient was five (range one to 17). Dose reduction was required in only 3.8% of cycles. Grade 4 neutropenia occurred in 19.6% of patients, but no grade 4 thrombocytopenia or anemia was reported. Febrile neutropenia was observed in only two (3.6%) patients and there were no life-threatening events. Grade 3/4 peripheral sensory-motor neuropathy was reported in 9% of patients. Other non-hematological toxicities, such as nausea and vomiting, myalgia and arthralgia, diarrhea, and mucositis, were uncommon. Partial responses were observed in eight (14.3%) patients and stable disease in 33 (58.9%). Median progression-free survival was 3.7 months [95% confidence interval (CI) 2.7–5.4] and median overall survival was 10 months (95% CI 6–13.4). Conclusions BMS-184476 was well tolerated at the dose of 60 mg/m2 and showed evidence of antitumor activity in previously treated NSCLC.

Background: Pharmacokinetic parameters (PHK) of low-dose weekly paclitaxel (PAC) are not well known, particularly when administered with the cytoprotective agent amifostine (AMI). Methods: Patients with non-small cell lung cancer (NSCLC) received PAC alone or PAC + AMI. Blood samples were drawn at the end of the infusion at 0, 0.25, 0.5, 1, 2 and 4 h for the measurement of plasma PAC using HPLC. Area under the concentration-time curve (AUC), the peak plasma concentrations (Cmax) and the residence time of paclitaxel in plasma at concentrations >0.1 µM (TPP ≧0.1) and >0.05 µM (TPP ≧0.05) were calculated using a two-compartmental model. ANOVA was used for statistical analysis. Results: Pharmacokinetic studies were completed for 43 doses among 11 patients receiving PAC alone and for 26 doses among 8 patients receiving the combination AMI + PAC (from the first to the fifth week). Statistically significant differences in all parameters except AUC were observed between the 2 treatment groups. A significantly higher Cmax was observed for patients receiving PAC + AMI versus PAC alone. Both TPP ≧0.1 and TPP ≧0.05 were also more prolonged in AMI + PAC cycles. Conclusion: AMI produces a prolongation in PAC plasma circulation time. Further specifically designed studies are needed to quantify the resultant effects on PAC’s efficacy and toxicity.

Purpose: To compare the survival benefit obtained with cisplatin plus gemcitabine, a cisplatin-based triplet, and nonplatinum sequential doublets in advanced non–small-cell lung cancer (NSCLC). Patients and Methods: Stage IIIB to IV NSCLC patients were randomly assigned to receive cisplatin 100 mg/m2 day 1 plus gemcitabine 1,250 mg/m2 days 1 and 8, every 3 weeks for six cycles (CG); cisplatin 100 mg/m2 day 1 plus gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 days 1 and 8, every 3 weeks for six cycles (CGV); or gemcitabine 1,000 mg/m2 plus vinorelbine 30 mg/m2 days 1 and 8, every 3 weeks for three cycles, followed by vinorelbine 30 mg/m2 days 1 and 8 plus ifosfamide 3 g/m2 day 1, every 3 weeks for three cycles (GV–VI). Results: Five hundred fifty-seven patients were assigned to treatment (182 CG, 188 CGV, 187 GV–VI). Response rates were significantly inferior for the nonplatinum sequential doublet (CG, 42%; CGV, 41%; GV–VI, 27%; CG v GV–VI, P = .003). No differences in median survival or time to progression were observed. Toxicity was higher for the triplet: grade 3 to 4 neutropenia (GC, 32%; CGV, 57%; GV–VI, 27%; P < .05); neutropenic fever (CG, 4%; CGV, 19%; GV–VI, 5%; P < .0001); grade 3 to 4 thrombocytopenia (CG, 19%; CGV, 23%; GV–VI, 3%; P = .0001); and grade 3 to 4 emesis (GC, 22%; GCV, 32%; GV–VI, 6%; P < .0001). Conclusion: On the basis of these results, CG remains a standard regimen for first-line treatment of advanced NSCLC.

Weekly paclitaxel was initially used to exploit the radiosensitizing properties of the drug. However, the observed improvement in therapeutic index with this regimen encouraged further use of weekly regimens, with and without radiotherapy, as a single-agent or in combination with other regimens. Single-agent weekly paclitaxel, at doses ranging from 50 to 200 mg/m 2 /week, has been associated with response rates of 23–56% with acceptable toxicity. Weekly paclitaxel has also been combined with carboplatin and vinorelbine in two-drug combinations and with cisplatin plus gemcitabine and cisplatin plus vinorelbine in three-drug regimens. Response rates with weekly paclitaxel in combination chemotherapy have ranged from 16 to 71%. Paclitaxel is particularly suited to combined modality therapy with radiation in non-small cell lung cancer, because of its modest toxicity profile, significant antineoplastic activity, ease of administration and potential for radiosensitization. Studies of weekly paclitaxel given together with radiotherapy, with or without carboplatin, have produced response rates of 71–86% with median survival durations of 17–20.5 months.

Background: Androgen-independent prostate cancer (AIPCA) is a difficult disease to treat. Fulvestrant has shown activity inhibiting estrogen receptor dimerization, and the androgen receptor has been shown to stimulate growth in prostate cancer cell lines. Case Report: A 79-year-old metastatic prostate cancer patient with AIPCA was treated with fulvestrant acetate with a loading dose strategy. Without recording any significant side effects, the prostate-specific antigen (PSA) level decreased from 154 ng/ml to 0.45 ng/ml 8 weeks after the first treatment administration. Conclusion: Fulvestrant was able to reduce the PSA level in this AIPC patient without any toxicity.

Preoperative chemotherapy has become an accepted treatment for stage IIIA (N2) non–small-cell lung cancer (NSCLC). The majority of induction regimens employ cisplatin, although the importance of cisplatin dose in combination is unclear. A randomized trial was conducted to address whether higher preoperative cisplatin doses result in improved survival and increased pathologic complete response in NSCLC. Patients with stage IIIA clinically enlarged and biopsy-proven N2 lesions were randomly assigned to receive either high-dose cisplatin (HDCP) (100 mg/m 2 ) or moderate-dose cisplatin (MDCP) (50 mg/m 2 ) in combination with ifosfamide (3 g/m 2 ) and mitomycin (6 mg/m 2 ). Disease was restaged after 3 cycles, and those patients with response or stable disease underwent thoracotomy. From March 1993 to February 1997, 83 patients were randomized: 46 received HDCP, and 37 received MDCP. Clinical characteristics were well matched. Radiographic response rate was 59% for HDCP patients and 30% for MDCP patients ( P = 0.01). Thoracotomy was performed in 71 patients (86%), 58 of whom had resectable disease. Complete resection rate was 61% in the HDCP group, and 51% in the MDCP group ( P = 0.5). Postoperative mortality was 11%. Pathologic complete response was observed in one patient who received MDCP. Median survival in the HDCP and MDCP groups was 13 and 11 months, respectively ( P = 0.3). In conclusion, higher radiographic response rate is observed in patients who receive HDCP, but this study fails to show any significant improvement in either overall survival or pathologic complete response in this group of patients.

Lung cancer involvement of the heart is not unusual, but in most cases is silent. Arrhythmia and electrocardiographic findings suggesting an acute myocardial infarction could be the first manifestation of myocardial infiltration by the tumour. Echocardiography could be a valuable tool to define the diagnosis in patients with lung cancer and newly diagnosed arrhythmia or ST-T wave alterations. When echocardiographics findings are not conclusive, magnetic resonance imaging (MRI) allows differentiation between tumour and myocardium.

The specificity and sensitivity of a tumor marker (TM) are important in establishing its potential clinical utility for a specific type of neoplasm. CA 15.3 is a TM specific for breast cancer; it is defined by two monoclonal antibodies (DF3 and 115D8), whose specificity, in disease-free follow-up patients, and sensitivity, in patients at diagnosis of first metastasis, have been evaluated in the present study and compared with those of carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). Serum concentrations of all three TMs were quantified in 618 individuals: 80 healthy controls, 421 patients with local breast cancer who became free of disease following locoregional treatment, and 117 patients with disseminated disease at diagnosis of metastasis. Radioimmunoassay (RIA) was the method employed, and the cut-off values obtained were 30 U/ml for CA 15.3, 5 ng/ml for CEA, and 120 U/I for TPA. The results showed CA 15.3 and CEA specificities to be analogous (95.7 and 95.5%, respectively). TPA specificity (81.9%) was lower (p < 0.001). During adjuvant therapy, CA 15.3 serum levels were seen to increase, followed by a normalization of concentration after terminating therapy. On the other hand, CA 15.3 and TPA sensitivities (64.1 and 67.5%, respectively) were greater than for CEA (44.4%, p < 0.01). It is concluded that CA 15.3 is a useful TM for breast cancer, as it offers a greater sensitivity than CEA and a higher specificity than TPA. Combining CA 15.3 and CEA fails to increase CA 15.3 sensitivity, while combining CA 15.3 with TPA increases false-positives and so likewise offers no additional benefit.

The purposes of this study are to evaluate the activity and safety of preoperative intensity-modulated radiotherapy and concurrent capecitabine and oxaliplatin (Xelox), the accuracy of preoperative magnetic resonance (MRI) for predicting pathologic results, and the correlation between carcinoembryonic antigen (CEA) and the existence of a pathologic complete response (pCR). Twenty-seven patients (pt) with T3/T4N0/N+ rectal cancer were included. Capecitabine was administered at 825 t.i.d. mg/m2 the days of the radiotherapy (RT), and oxaliplatin was administered weekly at 50 mg/m2. RT was planned to 50.4 Gy. Surgery was scheduled 6 to 8 weeks after completion of Xelox RT. Before the intervention, a pelvic MRI was performed and a CEA level was determined. After Xelox RT, 7 pt had pCR (26%), 2 pt progression disease, and 18 pt tumor downstaging. Presurgical MRI did not predict the pathological result in 21 pt. Main side effects were diarrhea grade (G) 3 in four pt, hand and foot G1 five Pt and G2 four pt. Paresthesias G1 ten pt, G2 seven pt, and leukopenia six pt G1. Median RT dose was 49.7 Gy (47.5–50.4 Gy). At a mean follow-up of 22.5 months, four pt presented metastatis. Mean pretreatment CEA was 6.8 ng/mL (2.1–17.0). A difference statistically significant when compared pretreatment CEA with presurgical CEA (p

PURPOSE We designed a prospective randomized trial to compare vinorelbine and cisplatin (NVB-P) with vindesine and cisplatin (VDS-P) and to evaluate whether the best of these regimens affords a survival benefit compared with vinorelbine alone (NVB), an outpatient regimen, in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Forty-five centers included 612 patients in this study: 206 on NVB-P, 200 on VDS-P, and 206 on NVB. Vinorelbine was administered at a dose of 30 mg/m2 weekly, cisplatin at 120 mg/m2 on days 1 and 29 and then every 6 weeks, and vindesine at 3 mg/m2 weekly for 6 weeks and then every other week. Treatment was continued until progression or toxicity. Four percent of the patients entered were ineligible and 59% had metastatic disease. RESULTS An objective response rate was observed in 30% of patients in the NVB-P arm versus 19% in the VDS-P arm (P = .02) and 14% in the NVB arm (P < .001). The median duration of survival was 40 weeks in the NVB-P arm, compared with 32 weeks in the VDS-P arm and 31 weeks in the NVB arm. Comparison of survival among the three groups demonstrated an advantage for NVB-P compared with VDS-P (P = .04) and NVB (P = .01). Neutropenia was significantly higher in the NVB-P group (P < .001), and neurotoxicity was more frequent with VDS-P (P < .004). CONCLUSION Since our results have demonstrated that NVB-P yields a longer survival duration and a higher response rate than VDS-P or NVB alone, with acceptable toxicity, this combination should be considered a relevant regimen in advanced NSCLC.

Twenty-two patients with metastatic breast carcinoma were treated with a combination of cisplatin (100 mg/m2 i.v. day 1) and etoposide (100 mg/m2 i.v. days 1-3). Eligible patients had measurable disease with normal organ functions, performance status < 3, age < 70 years and no previous chemotherapy for metastatic disease. Twenty patients were assessable for response. Objective responses were seen in 50% (95% confidence limits: 24.4-67.8). One patient achieved a complete response. Objective response was observed in patients with visceral metastatic disease and who had received anthracyclin-containing regimens in previous chemotherapy. Median survival after therapy was 55 weeks. Median time to progression was 23 weeks. Hematologic toxicity was limiting. Cisplatin plus etoposide is an active combination in advanced breast cancer.

Background Previous studies in sarcoma found that a composite gene signature, including high expression of nucleotide excision repair (NER) genes (XPG and/or ERCC1) and low expression of homologous recombination repair (HR) genes (BRCA1), identifies a highly sensitive population of patients with significantly improved outcome to trabectedin. This exploratory phase II trial evaluated a customized trabectedin treatment according to this gene signature in patients with non-small cell lung cancer (NSCLC) after the failure of standard platinum-based treatment. Methods Patients were selected according to their mRNA expression (elevated XPG and/or ERCC1, with low BRCA1) using the following values as cutoff: XPG = 0.99, ERCC1 = 3.47 and BRCA1 = 12.00. Trabectedin was administered as a 1.3 mg/m2 3-hour intravenous infusion every 3 weeks (q3wk). The primary efficacy endpoint was the progression-free survival rate at 3 months. Objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) was a secondary efficacy endpoint. Results Two of 18 evaluable patients (11.1%; 95% CI, 1.38–34.7%) achieved progression-free survival rate at 3 months. The primary efficacy objective (at least 3 of 18 patients being progression-free at 3 months) was not met, and therefore the trial was early finalized. No objective responses per RECIST were achieved. Four patients had stable disease. Median PFS was 1.3 months, and median overall survival was 5.9 months. Trabectedin was usually well tolerated, with a safety profile similar to that described in patients with other tumor types. Conclusions Customized treatment with trabectedin 1.3 mg/m2 3-h q3wk according to composite gene signature (XPG and/or ERCC1 overexpression, and BRCA1 underexpression) was well tolerated, but had modest activity in NSCLC patients pretreated with platinum. Therefore, further clinical trials with trabectedin as single agent in this indication are not warranted.

[EN] Introduction: Docetaxel plus prednisone is the current standard of care in first-line chemotherapy for metastatic hormone-refractory prostate cancer. However, there is no agent proven as effective after progression to standard docetaxel-based therapy. Platins and capecitabine have shown activity in this setting. Patients and Methods: A total of 14 patients were included in this prospective, single-center trial. All patients had progressed to first-line docetaxel-based treatment. Patients received oxaliplatin 100 mg/sqm on D1 and capecitabine 1000 mg/sqm/bid on days 1 to 14 every 21 days. Results: Median number of cycles was 3. No unexpected toxicity was observed. Only grade 3 toxicity reported was grade 3 anemia. Of the 14 patients, 3 presented grade 2 neuropathy which was spontaneously resolved. Prostate-specific antigenresponse rate was 57%, with a median time to progression of 14.5 weeks, and overall survival of 24 weeks. Conclusions: In the second-line setting, after receiving docetaxel-based chemotherapy, the combination of oxaliplatin and capecitabine offers promising activity with an excellent safety profile.

Metastatic melanoma is one of the most resistant tumors to standard chemotherapy approaches. The median overall survival of patients diagnosed with metastatic melanoma is lower than 9 months. Current approved treatments offer only marginal survival advantages. New immunotherapeutic targets have appeared recently trying to modulate the host immune response against the tumor. New targeted agents have changed the standard of care of other solid tumor types like breast cancer. Here, we discuss the new advances and achievements in the treatment of this highly resistant disease.

Nicotine acetylcholine receptors (nAChRs) are associated with resistance to gemcitabine, cisplatin and paclitaxel in non-small-cell lung cancer (NSCLC) cell lines. Three single nucleotide polymorphisms (SNPs) of CHRNA3, CHRNA5 and LOC123688 increase lung cancer risk. These SNPs may have influenced outcome in patients treated in our phase III trial. Stage IV NSCLC patients were treated with customized chemotherapy based on ERCC1 (excision repair cross-complementing 1) mRNA expression. Patients in the control arm received docetaxel/cisplatin; patients in the genotypic arm with low levels of ERCC1 received docetaxel/cisplatin; patients in the genotypic arm with high levels of ERCC1 received docetaxel/gemcitabine. DNA was extracted from lymphocytes, and CHRNA3 (rs1051730), CHRNA5 (rs16969968) and LOC123688 (rs8034191) SNPs were genotyped with the Taqman allele discrimination assay. A significant interaction was found for CHRNA3 and PS (P = 0.02). In patients with PS 0, CT patients had a better response than both CC (P = 0.01) and TT (P = 0.02) patients, and patients in the low genotypic group also had a better response (P = 0.01). When the CHRNA3 genotype was added in the multivariate analysis for progression-free survival, an improvement was observed in the low genotypic group in PS 0 patients (P = 0.02). PS 0 patients in the low genotypic group with the CT genotype attained an 84% response rate, 12.1-month progression-free survival, and 19-month median survival. CHRNA3 (rs1051730) genotyping can improve customized chemotherapy based on tumor assessment of ERCC1 mRNA in stage IV NSCLC with PS 0.

Platinum resistant ovarian cancer is a current challenge in Oncology. Current approved therapies offer no more of a 20% of response. New therapeutic options are urgently needed. Patients were treated with the combination of Pemetrexed 500 mg/m2 d1 and Gemcitabine 1000 mg/m2 d1, 8 in a 21 days basis. 10 platinum-resistant ovarian cancer patients were treated under compassionate use. Mean previous chemotherapy lines were 3.3. Mean administered cycles were 4. Mean CA 125 decrease was on average of 47%, with one patient experiencing a 95% decrease in her CA 125 level. 1 patient had a complete clinical remission, and 2, had partial radiological responses. Mean Progression free survival was 16.5 weeks, and Overall Survival was 21.2 weeks. Treatment was well tolerated. Deemd to the observed activity, the combination of Pemetrexed and Gemcitabine deserves deeper investigation in platinum-resistant ovarian cancer patients.

In the fight against cancer, new and more specific targets are needed. Here, we offer an example of a potential target that has not been widely studied, namely the syncytin protein. Syncytin is expressed mainly in the human placenta and is implicated in placental syncytiotrophoblast cell fusion. Not much is known about the role of syncytin in cancer, but the existing data call for more intense research. Its retroviral origin and particular tissue distribution make syncytin an interesting potential target in cancer therapy.

Bilateral synchronous testicular cancer is a rare disease and is usually associated with similar histological findings in each testicle. The standard therapy of bilateral testis cancer is generally considered to be inguinal orchiectomy. We present a case of synchronous bilateral testicular germ cell tumour, with different histology, initially treated with testis-sparing surgery. After pathology review, the margin of the partial orchiectomy was considered affected, and an inguinal orchiectomy was planned. Options for testis-sparing surgery are discussed.

Langerhans cell histiocytosis (LCH) is a poorly understood proliferative disease, with different patterns of clinical presentation. Currently it is classified according to the number and type of system involved and the degree of organ dysfunction. The aetiology of the disease remains uncertain, and in some cases the disease is polyclonal, suggesting a reactive condition. Many cytokines have been implicated in the pathogenesis of LCH. Different therapeutic approaches can be considered depending on the affected organ, including surgery, radiotherapy and chemotherapy. Long-term organ dysfunction may remain, despite disease control and/or eradication, making indefinite supportive treatment mandatory. Here we present a literature review on all of the aspects of the disease, treatment approaches and existing protocols, and finally an adult clinical case.

Background The number of elderly patients with cancer continues to increase. Approximately two-thirds of patients diagnosed with non-small cell lung cancer are 65 years, and nearly 50% are 70 years or older. The aim of our study was to discern whether clinical characteristics, toxicity, response rate, treatment and survival are different in patients enrolees 70 years of age and older with those in younger patients. Methods We reviewed the database of six clinical trials with different doublet combinations in the Spanish Lung Cancer Group from 1998 to 2005. Patient's characteristics, stage, histology, response and survival were obtained. Results All 1653 patients were studied; 280 patients (17%) were over 70. No significant differences were found between the two groups with respect to gender, stages, response rate or histological type. However, a greater squamous histological tendency was found in the older group. No differences were found in the median number of cycles administered. The only significant differences were in the greater percentage of grade III/IV neutropenia among patients older than 70. Febrile neutropenia was similar in both groups. Conclusions In our study, the oldest age group represented a small percentage of all patients included in clinical and pharmacogenetic trials. Although this might indicate bias when interpreting the results, age is not a contraindication to the treatment of the "fit" elderly. Patients with good performance status can be treated with standard doublets. We believe that special attention should be paid to cases with high risk of neutropenia. Research in this population should now be aimed at finding more selective treatments, based on the genetic differences that older patients have.

Estrogen (ER) and progesterone (PR) receptors were assayed in the center and the periphery of 24 primary breast cancers and correlated with seven morphological features of the tumors. Quantitative variations in ER and PR contents between center and periphery were not significant, and the major discordance rate of the receptor status was only 8.3% for ER and 12.5% for PR. Among all morphological features studied, only tumor cellularity was correlated with steroid receptors; thus 18 out of 19 ER-positive samples (p less than 0.005) and 15 out of 16 PR-positive samples (p less than 0.025) were tumor cellularity 2-3, and higher ER (p less than 0.003) and PR (p less than 0.007) levels were found in tumor cellularity 2-3. Our results indicate that steroid receptors should be assayed in samples with a high content of tumor cellularity, whether the sample is taken from the center or the periphery of the tumor.

Aging is associated with an increasing of comorbidity and at the time of lung cancer diagnosis patients present one or more other serious disease. The aim of the study is to evaluate tolerability, response and survival of weekly paclitaxel in elderly patients with advanced NSCLC and concomitant diseases.Patients with advanced NSCLC who were poor candidates to platinum-based therapy because of age65 years and coexistent illnesses received weekly paclitaxel over 1 hour at a dose of 80 mg/m2. Comorbidity was evaluated according to the Charlson scale, Kaplan-Feinstein index and the Cumulative Illness Rating Scale.A total of 57 patients (median age, 74 years; range, 65-84) were included. The overall response rate was 44%. Median survival was 7.8 months. Grade 3-4 toxicity was uncommon: neutropenia 1.8%, thrombocytopenia 1.8%, neuropathy 7%, hypersensitivity reaction 1.8%. Comorbidity indexes were useful to characterize better the population of elderly patients, but did not define a subgroup with worse prognosis.The low toxicity profile and efficacy of low-dose weekly paclitaxel justified its usage in this group of poor prognosis elderly patients with advanced NSCLC and comorbidities. A comorbidity index should be introduced in prospective oncological studies in the elderly to ensure compatibility.

Survival in advanced non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy is rather variable. Methylation-dependent transcriptional silencing of 14-3-3sigma, a major G2/M checkpoint control gene, could be a predictor of longer survival. A sensitive methylation-specific polymerase chain reaction assay was used to evaluate 14-3-3sigma methylation status in pretreatment serum DNA obtained from 115 cisplatin-plus-gemcitabine-treated advanced NSCLC patients. 14-3-3sigma methylation was observed in all histologic types in 39 patients (34%). After a median follow-up of 9.8 months, median survival was significantly longer in the methylation-positive group (15.1 vs 9.8 months; P = 0.004). Median time to progression was 8 months in the methylation-positive group, and 6.3 months in the methylation-negative group (P = 0.027 by the log-rank test). A multivariate Cox regression model identified only 14-3-3sigma methylation status and ECOG performance status (PS) as independent prognostic factors for survival. In an exploratory analysis, median survival for 22 methylation-positive responders has not been reached, while it was 11.3 months for 29 methylation-negative responders (P = 0.001). Methylation of 14-3-3sigma is a new independent prognostic factor for survival in NSCLC patients receiving platinum-based chemotherapy. It can be reliably and conveniently detected in the serum, thus obviating the need for tumor tissue analysis.

Background: Impaired DNA repair capacity may favorably affect survival in cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We investigated the association of survival with genetic polymorphisms in X-ray repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum group D (XPD), excision repair cross-complementing group 1, ligase IV, ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome proliferator-activated receptor γ, epidermal growth factor, methylene-tetra-hydrofolate reductase and methionine synthase. Patients and methods: One hundred and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patients treated with cisplatin/gemcitabine from different hospitals of the Spanish Lung Cancer Group were genotyped for 14 different polymorphisms in 13 genes. Polymorphisms were detected by the TaqMan method, using genomic DNA extracted from baseline blood samples. Results: Median survival was significantly increased in patients harboring XRCC3 241 MetMet: 16 months versus 10 months for patients with ThrMet and 14 months for those with ThrThr (P = 0.01). The risk of death ratio was significantly lower for MetMet than for ThrMet patients (hazard ratio, 0.43; P = 0.01). In the multivariate Cox model, XRCC3 241 remained an independent prognostic factor (hazard ratio: XRCC3 241 MetMet, 0.44; P = 0.01), and XPD 751 and XRCC1 399 also emerged as significant prognostic factors (hazard ratios: XPD 751 LysGln, 0.46, P = 0.03; XRCC1 399 ArgGln, 0.61, P = 0.04). No other association was observed between genotype and survival. Conclusion: XRCC3 241 MetMet is an independent determinant of favorable survival in NSCLC patients treated with cisplatin/gemcitabine. A simple molecular assay to determine the XRCC3 241 genotype can be useful for customizing chemotherapy.

Survival in advanced non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy is rather variable. Methylation-dependent transcriptional silencing of 14-3-3σ, a major G2/M checkpoint control gene, could be a predictor of longer survival. A sensitive methylation-specific polymerase chain reaction assay was used to evaluate 14-3-3σ methylation status in pretreatment serum DNA obtained from 115 cisplatin-plus-gemcitabine-treated advanced NSCLC patients. 14-3-3σ methylation was observed in all histologic types in 39 patients (34%). After a median follow-up of 9.8 months, median survival was significantly longer in the methylation-positive group (15.1 vs 9.8 months; P = 0.004). Median time to progression was 8 months in the methylation-positive group, and 6.3 months in the methylation-negative group (P = 0.027 by the log-rank test). A multivariate Cox regression model identified only 14-3-3σ methylation status and ECOG performance status (PS) as independent prognostic factors for survival. In an exploratory analysis, median survival for 22 methylation-positive responders has not been reached, while it was 11.3 months for 29 methylation-negative responders (P = 0.001). Methylation of 14-3-3σ is a new independent prognostic factor for survival in NSCLC patients receiving platinum-based chemotherapy. It can be reliably and conveniently detected in the serum, thus obviating the need for tumor tissue analysis.

Purpose Survival in patients with advanced non–small-cell lung cancer (NSCLC) who are treated with platinum-based chemotherapy is rather variable. Methylation-dependent transcriptional silencing of 14-3-3σ, a major G2-M checkpoint control gene, could be a predictor of longer survival. Patients and Methods A sensitive methylation-specific polymerase chain reaction assay was used to evaluate 14-3-3σ methylation status in pretreatment serum DNA obtained from 115 cisplatin-plus-gemcitabine–treated advanced NSCLC patients. Results 14-3-3σ methylation was observed in all histologic types of 39 patients (34%). After a median follow-up of 9.8 months, median survival was significantly longer in the methylation-positive group (15.1 v 9.8 months; P = .004). Median time to progression was 8 months in the methylation-positive group and 6.3 months in the methylation-negative group (log-rank test, P = .027). A multivariate Cox regression model identified only 14-3-3σ methylation status and Eastern Cooperative Oncology Group performance status as independent prognostic factors for survival. In an exploratory analysis, median survival for 22 methylation-positive responders has not been reached, whereas survival was 11.3 months for 29 methylation-negative responders (P = .001). Conclusion Methylation of 14-3-3σ is a new independent prognostic factor for survival in NSCLC patients receiving platinum-based chemotherapy. It can be reliably and conveniently detected in the serum, thus obviating the need for tumor tissue analysis.

Although no overall differences in survival have been observed between the many chemotherapy combinations in non-small-cell lung cancer, the clinical application of mRNA expression levels of amplified genes may disclose many genetic influences on cytotoxic drug sensitivity and enable clinicians to tailor chemotherapy according to each individual's gene profile. Specifically, the assessment of ribonucleotide reductase subunit M1 and thymidylate synthase mRNA expression levels might select patients who benefit from gemcitabine (Gemzar) or pemetrexed (Alimta) combinations. Until recently, clinical prognostic factors such as performance status, weight loss, and lactate dehydrogenase were the only parameters used to predict chemotherapy response and survival. However, accumulated data indicate that overexpression of genes involved in cancer glycolysis pathways plays an important role, and might be an independent mechanism of chemoresistance. The dysregulation of glycolytic genes is affected by growth signals involving the PI3K/Akt pathway and downstream genes such as hypoxia-inducible factor-1-alpha. One can thus envision that substantial improvements in therapeutic outcome could benefit from the integration of tailored ribonucleotide reductase-dependent chemotherapy, ribonucleotide reductase antisense therapy, and targeted therapy.