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Background. Taro (Colocasia esculenta L. Schott) is an economical import crop in Actopan, Veracruz, since it is exported to the United States of America (USA) and Canada. In Mexico, there is no regulation to implement traceability systems in agricultural products. Objective. To propose a traceability system in the supply chain of taro produced in Veracruz. Methodology. A questionnaire was designed to obtain information related to the production process; a second questionnaire asked about the packaging information; twenty-four producers and eight packinghouse managers were interviewed. Results and discussion. Producers have been growing taro for 10 years, they do not have any specific planting season and grow the variety Coco. No soil analysis is performed, irrigation is by flooding and the main pest is the mouse (Apodemus sylvaticus). Each producer makes an agreement with a packing house; the company performs the harvesting and then the packaging process. Wooden pallets are used for packaging; each pallet piles up 60 sacks of 18 kg of taro. Implications. The traceability model for the Mexican taro could be adapted to the traditional way of production in Mexico to increase competitiveness. Conclusions. The shipping label contains scarce information about the origin of the product. Links of the supply chain were identified and a traceability model for taro is proposed for first time.

e24098 Background: Patient reported outcomes measures (PROMs) represent a tool to objectively assess the health of cancer patients. PROMs may complement oncological evaluations by adding patients’ perspectives on their care priorities. Aim: to address more accurately the management of tumor related symptoms or drug related toxicities to bring he therapies more accurately to bring patients the best quality of life possible. Methods: Data was collected from our electronic registry after proper authorization and corresponding anonymization. Patients were systematically asked for symptoms as fever, diarrhea, dyspnea, vomiting and nausea. These symptoms were graded according to their severity using the Common Toxicity Criteria v5.0. Results: 49 patients admitted to Medical Oncology Hospitalization were included from July of 2020 to January 2021, 80% in advanced disease. Median age 63yo, 32% above 70 yo. Baseline data showed that 27% patients (19% stage IV) had fever at admission, decreasing at 48h to 4%. Patients who had vomiting at admission were 33% (28% stage IV) median grade 2 becoming 20% and grade 1 at 48h. Nausea was present in 49% patients (35% stage IV) at the time of admission with a median grade 1.5, and it decreased to 16% at 48h with a median grade 2. Diarrhea was reported in 12% patients (6% stage IV) median grade 2 at baseline and it was reduced to 10% median grade 1 at 48h. The median severity of diarrhea at admission was 2 and only 1 at 48h. At admission, 33% (all stage IV) of patients presented dyspnea with a median grade 3, while at 48h it was present in 26% of patients and reduced to median grade 2. Conclusions: By systematically measuring symptoms, patients achieved better control of diarrhea, dyspnea, vomiting and nausea after admission. It should be noted that nausea was the variable that decreased the most at 48h, followed by fever, vomiting, dyspnea and diarrhea. All patients with stage IV disease had dyspnea and most of them had nausea and vomiting. These results reflect that these symptoms are more usual in patients with advanced disease compared to those with localized disease. PROMS also help us educate patients by teaching them how to manage treatments, thus improving therapeutic adherence.

e14034 Background: Cancer patients under cytotoxic treatment with fever used to have an average time of antibiotics administration of 11h (median 3h43min) when admitted and identified at the Emergency Room Service in the third level Central University Hospital of Asturias. International guidelines recommend antibiotic administration in the first hour: the so called “Golden Hour”. This delay implies an increase in patient morbidity as well as the cost of managing this complication. Methods: Data was collected from our electronic registry after proper authorization and corresponding anonymization. Pareto and fishbone diagrams were built to point out the possible causes and to stratify them in related subgroups. We measured: Number of visits to ER with fever and Number of inpatients with Febrile Neutropenia diagnosis, Time from the admission to antibiotic administration, Average stay of inpatients with Febrile Neutropenia diagnosis. A protocol associated to electronic tools and validated international scores was designed for patients at Febrile Neutropenia risk and launched on March 2019. Results: 66 patients were included since January 2018. Baseline data showed that the median time to antibiotics indication was 3h50min (average 4h38min) with a median delay of 18min to the administration (average 1h06min), a median of 3h54min (average 10h09min) time to antibiotic administration. When the protocol was activated, median time to antibiotic indication was 30min (average (1h08min) with a median 41min (average 40min) delay in administration, and a median of 1h30min (average 1h42min) time to antibiotic administration. Those with activation of the protocol had average length of stay of 1d13h40min vs. 5d11h18min in those to whom this protocol was not applied. Conclusions: A continuous evaluation effort and the design of appropriate protocols and interventions will increase the efficiency of the oncology patient care process with febrile neutropenia, by reducing unnecessary variability and costs.

665 Background: It is widely known the causal relationship establised between tobacco use and the development of renal cancer is widely known. Nevertheless, the impact of smoking on the efficacy and safety of anti-angiogenic drugs is unclear. Sunitinib is a tyrosine kinase inhibitor with proven efficacy metastatic renal cell carcinoma (mRCC). Methods: A retrospective analysis was carried out including 194 mRCC patients (pts) who received Sunitinib in a single Institution (Hospital Universitario Central de Asturias) with a high incidence of this disease. The aim of this study is to explore the impact of the smoking habit on treatment response in terms of progression‐free survival (PFS) and overall survival (OS). Results: Most patients presented clear cell histology (92%). Smoking status: 42% (n=82) never‐smoker, and 39% (n=76) former‐smoker and 19% (n=36) current‐smoker. Male predominance 78% (n=145). Median age was 65 (range: 40‐84). Survival analysis favors patients with a history of tobacco use. There was no significant difference in PFS between never‐smoker vs ever-smoker groups: median PFS 8.13 months (95% IC: 4.75‐11.52), vs 12 months (95% IC: 9.97‐14.03) was found respectively (p=0,086). Fewer than 10% developed grade 3 toxicity. A significative improvement in OS in patients ever-smokers: median OS 16.23 months (95% IC: 12.22‐20.25) vs 26.46 months (95% IC: 16.21‐36.73) (p=0.044). The advantage observed in patients with any smoking history became more evident for poor prognosis cases. A median OS 5.03 months (95% IC: 0.84‐9.23) vs 14.03 months (95% IC: 7.81‐20.26). A median PFS 6.4 months (95% IC: 2.53‐10.27) vs 13.33 months (95% IC: 1.14‐26.19) p > 0.05. Conclusions: In this series, tobacco seems to play a role on the efficacy and safety of anti‐angiogenic agents in mRCC. However, additional prospective studies in well‐balanced populations are required to confirm this data.

Treatment options for patients with high-grade pancreatic neuroendocrine tumors (pNET) are limited, especially for those with progressive disease and for those who experience treatment failure. Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has been approved for the treatment of patients with low- or intermediate-grade advanced pNET. In the randomized phase III RADIANT-3 study in patients with low- or intermediate-grade advanced pNET, everolimus significantly increased progression-free survival (PFS) and decreased the relative risk for disease progression by 65% over placebo. This case report describes a heavily pretreated patient with high-grade pNET and liver and peritoneal metastases who achieved prolonged PFS, clinically relevant partial radiologic tumor response, and resolution of constitutional symptoms with improvement in Karnofsky performance status while receiving a combination of everolimus and octreotide long-acting repeatable (LAR). Radiologic and clinical responses were maintained for 19 months, with minimal toxicity over the course of treatment. This case supports the findings that the combination of everolimus plus octreotide LAR may be considered for use in patients with high-grade pNET and progressive disease. Although behavior and aggressiveness are different between low- or intermediate-grade and high-grade pNET, some high-grade pNET may express mTOR; hence, everolimus should be considered in a clinical trial.

IntroductionPegylated liposomal doxorubicin (PLD) is currently the reference treatment for platinum-resistant ovarian cancer. The combination of PLD and gemcitabine and the administration of gemcitabine at a fixed dose rate infusion (FDRI) seem to have additive activity in this disease setting. We have launched a phase Ib study with the combination of FDRI gemcitabine followed by PLD in recurrent ovarian cancer with a platinum-free interval of less than 1 year, with parallel pharmacokinetic and pharmacogenetic studies.MethodsThe starting dose of gemcitabine was 1500 mg/m2, 10 mg/m2per minute, every 2 weeks (±250 mg gemcitabine titration depending on toxicity), followed by PLD 35 mg/m2every 4 weeks. Gemcitabine pharmacokinetics and equilibrative nucleoside transporter 1, deoxycytidine kinase, and ribonucleotide reductase M1 gene expression levels were studied.ResultsThirty-five patients were treated at 3 different dose levels (DL). Dose level 1 was not tolerated. Nonfrail patients continued to be treated at DL-1 (G 1250 mg/m2on day 1 and PLD 35 mg/m2on days 1 and 15). Of 10 evaluable nonfrail patients, 4 displayed dose-limiting toxicity. Frail patients were treated at DL-2 (G 1250 mg/m2on day 1 and PLD 35 mg/m2on days 1 and 15). Of the 12 evaluable frail patients, 3 developed dose-limiting toxicity. Neutropenia, palmar-plantar erythrodysesthesia and stomatitis were the most common toxicities. The response rate was 42.8% (95% confidence interval [CI], 34.5%-51.1%), with 17.1% (6/35) complete responses and 25.7% (9/35) partial responses. The median progression-free survival was 7.7 months (95% CI, 2.2-13.1). The median overall survival was 13.9 months (95% CI, 9.4-18.4). The administration of PLD after gemcitabine did not influence gemcitabine pharmacokinetics or its metabolites. The addition of PLD to gemcitabine caused a larger and longer induction of the ribonucleotide reductase M1 gene. Patients with higher baseline levels of deoxycytidine kinase had longer progression-free survival.ConclusionThe recommended dose for a phase II study of patients with recurrent ovarian cancer having poor prognosis is PLD, 35 mg/m2on day 1, and gemcitabine, 1000 mg/m2on days 1 and 15 delivered at an FDRI of 10 mg/m2per minute in 28-day cycles.

Studies with the gemcitabine/vinorelbine (GV) or the gemcitabine/docetaxel (GD) combinations have shown similar efficacy and less toxicity compared to platinum-based chemotherapies, in patients with advanced non-small-cell lung cancer (NSCLC). The present trial was designed to test the efficacy and safety of both, GV and GD, combinations. Chemotherapy-naive patients (n = 39) ≤75 years of age, KPS ≥ 60% and adequate hematological, renal and hepatic function were randomly assigned to receive G 1,000 mg/m2 + either V 25 mg/m2 or D 35 mg/m2 (all of which were administered i.v.) on days 1 and 8 every 21 days. Baseline characteristics were comparable in GV (n = 20) and GD (n = 19) groups. Results indicated objective response of 7 (35%) vs 6 (31%) patients and median time-to-treatment failure of 120 versus 90 days in the GV and GD arms, respectively. The most common non-hematological toxicities were (GV vs GD): grade 2–4 pulmonary toxicity in 1 (5%) vs 7 (37%); grade 2–3 diarrhea 0 versus 4 (21%) and edema 1 (5%) vs 3 (16%); grade 3–4 hematological toxicities occurred in 3 (15%) vs 1 (5%) patients. Our results indicate that the combination of gemcitabine/docetaxel does not have a favorable safety profile with this schedule of administration, particularly in terms of pulmonary toxicity.

To evaluate possible improvement in objective response of adding vinorelbine (V) to the combination of cisplatin/gemcitabine (CG) in induction chemotherapy for stage III NSCLC, patients (n=154) agedor =75 years, Karnofsky indexor =70%, were stratified by stage (IIIA versus IIIB) and randomly assigned to receive: C (50mg/m(2) i.v.) plus G (1250mg/m(2) i.v.) or CG plus V (25mg/m(2) i.v.). All drugs were administered on days 1 and 8 of an every 3-week cycle. At conclusion, local treatment (LT) with surgery and/or radiotherapy was scheduled. The results indicated that, following a median of 3 cycles, the overall efficacy was 65% in the CG and 61% in the CGV group. Most patients in both groups received radiotherapy as part of their LT. Pathological complete response was confirmed by surgery in 18% in the CG and 25% in the CGV group. Median progression-free survival was 368 days in the CG and 322 days in the CGV group. There were no statistically significant differences in toxicities between groups. We conclude that the CG and CGV combinations had similar efficacy and moderate toxicity, without accruing to the triplet combination.

Orientador: Gláucia Maria Pastore Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos Resumo: A batata-doce roxa (Ipomoea batatas (L.) lam) e? considerado rica fonte de carboidratos, fibras, minerais, vitaminas e antioxidantes, como compostos feno?licos e antocianinas, que tem sido associadas com a protec?a?o de ce?lulas e tecidos no organismo prevenindo e reduzindo o risco de doenc?as cro?nicas. O presente trabalho teve como objetivo determinar os compostos bioativos e avaliar as propriedades antioxidantes presentes no extrato liofilizado de batata-doce roxa. Foram caracterizadas as propriedades químicas com medidas de pH e sólidos solúveis da matéria-prima; foi otimizada a extração das antocianinas de batata-doce roxa, foi determinada o teor de antocianinas monoméricas totais e o extrato otimizado foi purificado e analisado no espectrômetro de massas, sendo encontrados os compostos pelargonidina, cianidina e petunidina. Foi determinada o teor de fenóis totais, flavonóides totais, e atividade antioxidante in vitro do extrato liofilizado de batata-doce roxa. As condições ótimas de extração ocorreram em 55% de etanol, pH 2 a 80 ºC com valor de antocianinas totais monoméricas de 341,85mg/100gEL em base seca. As variáveis de extração de pH e concentração de etanol mostraram ser estatisticamente significativas. Os teores de compostos bioativos do extrato liofilizado de batata-doce roxa para fenóis totais foi de 248,89 mgEAG/100g de amostra, flavonóides totais de 104,14 mgEC/100g de amostra, a atividade antioxidante in vitro a través do DPPH expressado em IC50 foi de 5,61 ?g/mL e expressado em Trolox equivalente foi de 150 ± 0,02 mgTE/g b.s e a atividade antioxidante através do ORAC foi de 141,89 mgTE/g de extrato liofilizado Abstract: The purple sweet potato (Ipomoea batatas (L.) Lam) is considered rich source of carbohydrates, fiber, minerals, vitamins and antioxidants such as phenols and anthocyanins which has been associated with protective cells and tissues in the body and preventing reducing the risk of chronic diseases. This study aimed to determine the bioactive compounds and evaluate the antioxidant properties present in the freeze-dried extract of purple sweet potato. Chemical properties with soluble solids and pH measurements were characterized feedstock; has optimized the extraction of purple sweet potato anthocyanins was determined the content of anthocyanins total monomeric and optimized extract was purified and analyzed in a mass spectrometer, and found the pelargonidin compound, cyanidin and petunidin. It was determined the total phenolic content, total flavonoids and antioxidant activity in vitro of the lyophilized extract of purple sweet potato. The optimum extraction conditions occurred in 55% ethanol, pH 2 at 80 ° C with the amount of monomeric anthocyanins 341,85mg / 100gEL on a dry basis. The pH extraction variables and ethanol concentration shown to be statistically significant. The levels of bioactive compounds of the lyophilized extract of purple sweet potato total phenol was 248.89 mgEAG / 100g sample, total flavonoids from 104.14 MgEC / 100g sample in vitro antioxidant activity to the slant of DPPH expressed in IC50 was 5.61 mg / mL and expressed in equivalent Trolox was 150 ± 0.02 mgTE / g bs and the antioxidant activity through the ORAC was 141.89 mgTE / g of freeze-dried extract Mestrado Ciência de Alimentos Mestra em Ciência de Alimentos

To assess the efficacy of carboplatin when used as a single agent in patients with advanced non small cell lung cancer (NSCLC) and who are refractory to chemotherapy with a non-platinum combination, we recruited patients (n=40) NSCLC patients, 36 of whom were males, with an overall median age of 59 years (range 39-79) and Karnofsky Performance Status of 70% (range 60-90%). At baseline, the patients had a median of one disease site (range 1-3) and had received a median of one prior regimen (range 1-2). Carboplatin was administered (i.v.; AUC=6) every 3 weeks until disease progression or non-acceptable toxicity was reached. In total 169 cycles were administered (median 4 cycles/patient; range 1-8). Main toxicities were grade 2-3 anemia and grade 4 thrombocytopenia (22.5% of patients). Overall clinical response rate was 10% (4 partial responses); 26 patients (65%) had stable disease and 8 (20%) had disease progression. Median time to progression and median survival time were 90 and 187 days, respectively. One year survival rate was 13%. We conclude that carboplatin shows minimal toxicity with a discrete anti-tumor activity in patients with NSCLC and who are refractory to non-platinum combinations.

The objective of this study was to assess whether adding cisplatin to gemcitabine/vinorelbine combination improves the clinical outcome in patients with non-small-cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC; ageor = 75 years: Karnofsky performance statusor = 60%, and with adequate hematological, renal and hepatic function, were randomized into 2 treatment groups to receive Gemcitabine 1250 mg/m2 + vinorelbine 30 mg/m2 (GV group), or cisplatin 50 mg/m2 + gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 (CGV group). All drugs were administered on days 1 and 8 every three weeks: From September 1999 to March 2003, 114 patients were enrolled. No statistically significant difference was observed in GV vs CGV group in objective response (37 versus 47%, respectively; P = 0.5), median time to progression (5 versus 5.8 months; P = 0.6), overall survival (9 versus 10 months; P = 0.9) and 1-year survival (26 versus 28%; P = 0.9). Conversely, toxicities were significantly higher for CGV, including grade 3-4 neutropenia (24 versus 45%); neutropenic fever (4 versus 14%, including one toxic death); grade 3-4 thrombocytopenia (2 versus 14%); and grade 3-4 emesis (2 versus 14%). Our results suggest that the combination of gemcitabine and vinorelbine is less toxic than three-drug combination with cisplatin while showing similar efficacy.

BACKGROUND This naturalistic cross-sectional survey of patients with severe mental illnesses explores the association between important variables and obesity, extreme obesity, diabetes mellitus type 2, hypertension, and hyperlipidemia in the clinical environment. METHOD Weight and height were obtained from 560 patients with severe mental illnesses (including DSM-IV schizophrenia, schizoaffective disorder, bipolar disorder, and major depressive disorder) at central Kentucky inpatient and outpatient facilities to estimate their body mass index (BMI). Chart diagnoses of diabetes mellitus, hypertension, and hyperlipidemia were obtained. RESULTS When comparing the patients with severe mental illnesses with Kentucky adults from the general population, the odds ratio (OR) of obesity (BMI > or = 30 kg/m(2)) was 2.6 (95% confidence interval [CI] = 2.2 to 3.0), and the OR of diabetes mellitus was 2.9 (95% CI = 2.3 to 3.6). Female gender, African American race, early start of psychiatric medication, and long psychiatric medication duration were significantly associated with obesity. Current alcohol and nicotine use exhibited significant ORs of obesity lower than 1, particularly in males. Obesity was closely associated with hypertension, type 2 diabetes mellitus, and hyperlipidemia. These complications were closely associated with each other and may indicate a further progression of obesity after aging. CONCLUSIONS These results suggest a complex pattern of variables that may influence the development of obesity and its complications in patients with severe mental illnesses, but they need replication. The major factors associated with obesity appear to be a long-term illness or treatment duration and substance use. The former may be more important in females, while the latter may be more important in males. Clinical diagnoses (schizophrenic or mood disorders) or current treatment did not appear to be fundamental factors.

Irinotecan (CPT-11), a semisynthetic derivative of camptothecin, is active in the treatment of non-small cell lung cancer (NSCLC). In this report we describe our experience with this drug when used as a single agent in patients with advanced NSCLC refractory to chemotherapy with platinum and taxanes. Nineteen NSCLC patients (thirteen males and six females; 53% adenocarcinoma and 26% squamous cell carcinoma) with a median age of 52 years (range 34-71) and a Karnofsky performance status of 60% (60-80%) were included in the study. At baseline, the patients had a median of two disease sites and had been treated with a median of two prior regimens. Irinotecan was given at a dose of 100 mg/m(2) i.v.) weekly for 4 weeks followed by 1 week of rest. A total of 123 weekly infusions were administered, and each patient received a median of 4 weeks of treatment (range 1-32). All patients were evaluated by intention-to-treat analysis for efficacy and safety. Main toxicities reported were grade 3 neutropenia (10% of patients), diarrhea (10% of patients), and grade 4 thrombocytopenia (5% of patients). The overall clinical response rate was 16% (95% CI: 8-24) with three partial responses and 9 (47%) patients with stable disease. The median time to progression and the median survival time were 7 and 15 weeks, respectively. In conclusion, weekly irinotecan showed antitumoral activity and minimum toxicity in NSCLC patients refractory to platinum and taxanes.

For nearly the past two decades, cytokines (CKs) have been the only systemic treatment option available for advanced renal cell carcinoma (RCC). In recent years, tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity on this tumour. Our purpose is to describe one centre's experience with the use of CKs and TKIs in the treatment of patients with advanced RCC.This study was designed as a retrospective chart review of RCC patients who were treated with CKs and/or TKIs in our department between July 1996 and June 2008. Efficacy and toxicity were assessed using World Health Organization (WHO) criteria. The Kaplan-Meier method was used to estimate progression-free (PFS) and overall (OS) survival.Ninety-four patients were classified into three groups depending on the modality of treatment administered: 46 were treated with CKs alone and/or chemotherapy (27 with immunotherapy, one with chemotherapy and 18 with both), 28 with TKIs alone (25 with sunitinib and 13 with sorafenib) and 20 with TKIs in second-line treatment following failure with CKs (17 with sunitinib, eight with sorafenib, four with bevacizumab and one with lapatinib). The median age was 60 years in the CK group and 65 and 62, respectively, in TKI in first and second-line treatment groups. Eighty-five percent of patients treated with CKs and 75% in the TKI group in first-line treatment and 80% in second-line treatment were men. Overall, 89% of patients had favourable risk, and 11% had intermediate risk. All patients were considered evaluable for toxicity. The main grade 3-4 (%) toxicity was asthenia for both groups, (ten in TKIs and 15 in CKs). Other grade 1-2 toxicities were mucositis (39), bleeding (8), hypertension (19), skin toxicity (33) and hypothyroidism (12.5) associated with TKIs; and anaemia (33), cough (29), asthenia (39) and emesis (14) associated with CKs. The objective response rate among 80 patients evaluable for activity was 10.6% with CKs and 46.5% and 35%, respectively, with TKIs in first- and second-line treatments. Disease stabilisation with CKs was recorded at 59% of patients and with TKIs 25% and 50% in first- and second-line treatment groups, respectively. The median progression-free survival (PFS) with CKs was 122 days [95% confidence interval (CI) 82-162] and with TKIs 201 days (65-337) in the first and 346 days (256-436) in second-line treatment groups. The median overall survival (OS) was 229 days (142-316) and 2,074 days (1,152-2,996) for patients treated with CKs and TKIs.Our results are in line with the activity and survival rates previously reported in the literature regarding the use of TKIs for patients with advanced RCC in first- and second-line treatment, which has demonstrated an acceptable toxicity level.

Topotecan, a semi-synthetic camptothecin analogue with topoisomerase I interaction, has shown to be an active agent in the treatment of advanced refractory lung cancer. This paper describes the authors' experience with this drug when used as a single agent in patients (pts) with advanced non-small cell lung cancer (NSCLC) refractory to platinum- and taxane-containing chemotherapy regimens. Thirty-five patients with NSCLC refractory to previous chemotherapy and KI ≥ 60% were included in the study. Their characteristics are as follows: median age of 52 years (range 43-69) and Karnofsky PS of 70 (60-80); 27 were male and 8 were female. Twenty-one (60%) patients had adenocarcinoma; eleven (31.4%), squamous cell, and three (8.5%), undifferentiated carcinoma. There was a median of two disease sites and two prior chemotherapy regimens. Topotecan was administered at a dose of 1.25 mg/m(2) I.V. daily for 5 days, repeated every 21 days until disease progression, maximal response, or intolerable toxicity. After 73 cycles, patients received a median of 2 treatment cycles (1-9). All patients except one were considered evaluable for toxicity; eight episodes (24%) of nausea/vomiting and two episodes (6%) of grade 1-2 asthenia, respectively, were reported. Four (12%) patients developed grade 1-2 anemia and two (6%) subjects suffered grade 3 anemia. Seven (21%) patients had grade 1-2 neutropenia and one (3%) presented grade 5 neutropenia. In 33 patients evaluable for activity of the 35 subjects included in the study; one (2.8%) presented a partial response; nine (25.7%) had stable disease, and 23 (65.7%) exhibited disease progression. Median time to progression and overall survival were 54 (12-210) and 70 (12-324) days, respectively. Intravenous topotecan at that dose and administration schedule displays scant activity in terms of response rate in individuals with advanced NSCLC previously treated with platinum and taxanes. The role and usefulness of chemotherapy in this setting warrants further investigation and confirmation through comparative studies.

e12609 Background: There are numerous surveys on prevalence of cancer-related pain. However, given the limitation of small patient samples, results are not strong enough to determine pain prevalenc...

La cirugía representa el tratamiento curativo de elección para los pacientes que son diagnosticados de carcinoma no microcítico de pulmón en estadio local. Sin embargo, gran parte de ellos experimentan una recurrencia de su enfermedad lo que ha llevado al empleo de opciones terapéuticas tanto locales como sistémicas con el ánimo de mejorar las posibilidades de curación. Durante las últimas décadas diversos estudios comparativos heterogéneos y varios meta-análisis publicados en los años 95 y 97 no demostraron de forma significativa una ventaja al asociar la quimioterapia y/o radioterapia adyuvante a la cirugía. Desde entonces y hasta nuestros días otros trabajos realizados con un número mayor de pacientes y empleando una quimioterapia más eficaz basada en combinaciones de platino, coinciden en describir un beneficio con su utilización aunque no de forma unánime. Más recientemente, un nuevo meta-análisis recopilando la mayoría de los estudios antes mencionados ha confirmado de forma significativa una mejoría absoluta del 4% en la supervivencia global de los pacientes sometidos a quimioterapia adyuvante, especialmente en los estadios patológicos II-III tras cirugía y tratados con regímenes que incluyen cisplatino y vinorelbina. Queda por ser determinado el papel que desempeñan otros agentes como el uracilo/tegafur así como la radioterapia en el contexto adyuvante.

According to premarketing studies, at least 1% of ziprasidone-treated patients exhibited hypertension; however, this figure is not necessarily attributable to the drug. A PubMed/MEDLINE search yielded no articles describing hypertension as a possible adverse event associated with oral ziprasidone therapy. We describe a 53-year-old African-American woman with hypertension and schizophrenia whose blood pressure increased during ziprasidone therapy. She experienced no similar blood pressure increases during therapy with four other atypical antipsychotics. Her mean systolic blood pressure during ziprasidone treatment (158 mm Hg) was significantly higher than before (141 mm Hg) and after (135 mm Hg) treatment. Also, her mean diastolic blood pressure during ziprasidone treatment (88 mm Hg) was significantly higher than after treatment (79 mm Hg). Linear regression analysis demonstrated that the patient's systolic blood pressure increased significantly with ziprasidone dose (regression coefficient [B] = 0.22 mm Hg x day/mg, 95% confidence interval 0.10-0.34, p=0.001). Thus, after adjusting for the effect of antihypertensive doses, an increase of 40 mg/day in ziprasidone yielded an increase of 8.8 mm Hg in systolic blood pressure. For unknown (perhaps genetic) reasons, this patient may have been particularly sensitive to ziprasidone. Clinicians prescribing ziprasidone in patients with hypertension should be aware that their hypertension could worsen with the addition of ziprasidone. If this occurs, replacement of ziprasidone with a different antipsychotic should be considered.

Durante las últimas décadas el tratamiento adyuvante anti-hormonal de elección para las pacientes post-menopáusicas con diagnóstico de carcinoma de mama localizado y con receptores hormonales positivos ha sido el tamoxifeno al disminuir de una forma significativa el riesgo de muerte por tumor. Más recientemente, una serie de estudios comparativos utilizando tres agentes inhibidores aromatásicos de tercera generación y diferentes esquemas de administración, bien tras la cirugía inicial del primario o después de 2-3 años o 5 años de tamoxifeno, han demostrado una ventaja en la supervivencia libre de enfermedad con respecto al tamoxifeno. Los efectos adversos acompañantes describen perfiles de toxicidad distintos entre ambos tipos de tratamiento anti-hormonal, siendo más comunes y frecuentes los fenómenos osteo-musculares y cardiovasculares en el grupo de pacientes tratadas con inhibidores aromatásicos así como los tromboembólicos y patología endometrial en el grupo tratado con tamoxifeno. La mejor estrategia para la administración, la forma de prevenir los efectos adversos y el tipo de pacientes que más se pueden beneficiar de los inhibidores aromatásicos, quedan por ser definidos con mayor precisión.

INTRODUCCIÓN: La quimioterapia (QT) y la radioterapia torácica (RT-T) constituyen el tratamiento estándar para los pacientes con carcinoma de pulmón no microcítico localmente avanzado inoperable/irresecable (CPNM-I) aunque el mejor esquema de administración está por determinar. MATERIAL Y MÉTODOS: Se ha realizado un estudio prospectivo en pacientes con CPNM-I estadio IIIA o IIIB no quirúrgicos, para determinar la tolerabilidad y el control local utilizando el siguiente esquema: 7 ciclos de Docetaxel (D: 20 mg/m²) o Paclitaxel (P: 60 mg/m²) semanal, concurrente con RT-T (2 Gy diariamente de lunes a viernes, dosis total 70 Gy, durante 7 semanas) después de 3 ciclos de QT de inducción basada en cisplatino (CDDP+gemcitabina +/-vinorelbina). RESULTADOS: Desde Diciembre 1999 a Diciembre 2004, cincuenta y dos pacientes de 129 tratados con QT de inducción fueron considerados elegibles para el análisis: 27 recibieron Docetaxel y 25 Paclitaxel. La mediana de semanas de tratamiento administradas fue 5 para el D (rango 7-3) y 6 para el P (7-1). 40% (D) y 58% (P) de los pacientes en cada grupo completaron 7 semanas y las dosis programadas del tratamiento. La toxicidad registrada incluye (D/P;%): Esofagitis grado (G)I (22/18); GII (25/29), GIII (30/8), neumonitis G I-II (14/5), diarrea GI-II (14/0). La progresión local y mediana de tiempo hasta la progresión local fue 41% y 180 días para D y 46% y 240 días para P. CONCLUSIONES: Los resultados de este pequeño estudio prospectivo sugieren que la asociación concurrente de radioterapia torácica con docetaxel o paclitaxel semanal ofrece un control similar de la enfermedad así como una tendencia a una menor toxicidad no hematológica con paclitaxel.

e19034 Background: RFC is the major transport system in mammalian cells for folate cofactors and antifolate therapeutics. The aim of this study was to assess the predictive value of RFC expression in patients receiving pemetrexed for advanced NSCLC. Methods: The study was carried out in a population of 48 patients with advanced NSCLC which have received pemetrexed monotherapy in second and third line. RFC expression was assessed using a two-step model of immunohistochemical staining in paraffin-embedded tissue samples. Results: RFC expression was detected in 16 (33%) patients. In the global population, the median progression free survival (PFS) and the median overall survival (OS) were 3.3 and 6.5 months respectively. The subgroup of patients with expression of RFC had a tendency to better median PFS (4.5 vs 2.8 months; p=0.926) and median OS (11.7 vs 4.8; p=0.150). In patients with adenocarcinoma histology and RFC expression median OS after treatment with pemetrexed was 14.4 months versus 5.0 in those with adenocarcinoma but without RFC expression (p=0.039). Conclusions: These results suggest the possible relation between RFC expression and response to treatment with antifolates (pemetrexed) independently of the tumor histology. Further studies are required to confirm these results.

e18044 Background: PEM and VRLO have shown high activity and good safety profile when given as single agent chemotherapy for NSCLC. Platinum combinations are considered the standard of care of first-line advanced NSCLC treatment. However, some patients cannot receive platinum salts, being treated with non-platinum combinations as an alternative treatment option. PEM is indicated for the 1st-line treatment of patients with locally advanced or metastatic NSCLC other than predominantly squamous cell histology. VRLO is indicated for stage III-IV NSCLC and has shown efficacy in all histology subgroups. Their combination could offer a treatment option in non-squamous 1st-line NSCLC. Methods: A phase I study is being conducted to determine the maximal tolerated dose (MTD) of PEM on day 1 plus VRLO given on days 1 and 8, with 3-weeks cycles as 1st-line treatment in locally advanced or metastatic non-squamous NSCLC pts. Results: As of Jan-2012, 18 pts (M/F: 13/5, median age 61, all PS 0-1) had received 104 cycles in 4 dose levels (DL): VRLO (mg/m2)/PEM (mg/m2): 60/500 (5 pts, DL1), 70/500 (7 pts, DL2), 60-80/500 (3 pts, DL3), 80/500 (3 pt-DL4). Safety: dose limiting toxicity as defined per protocol was neutropenia gr 4 with febrile neutropenia at DL2. Other toxicities were: neutropenia gr 3 (3 pts), gr 2 (2 pts); leukopenia gr 2 (3 pts). Other adverse events included: vomiting (gr 3 / 1 pt) (gr 2 / 5 pts); gr 2 asthenia (5 pts); constipation (gr 2 / 1 pt) (gr 1 / 2 pts); diarrhea (gr 1 /3 pts); fever (gr 1/1 pt); alopecia (gr 1/ 1 pt). Efficacy in 15 evaluable pts: CR, 0 pts; PR, 9 pts; NC, 3 pts; PD, 2 pts. Overall response rate, 60% (73% clinical benefit). Conclusions: The administration of PEM plus VRLO is feasible, the MTD being reached at 80/500 mg/m2. Further exploration of the combination will be planned after final analysis.

84 Background: Docetaxel is a standard treatment for hormone-refractory prostate cancer. Preclinical-clinical studies suggest that the determination of the BIII-tubulin is associated with response to taxanes. This study analyzes the role of that subunit of microtubules in prostate biopsies of patients with HRPC treated with docetaxel. Methods: Thirty two patients with prostate biopsy who received docetaxel in first-line chemotherapy between 2006 and 2011 were included in this retrospective cohort analysis. The clinic-pathological characteristics, PSA response, progression-free survival (PFS) and overall survival (OS) were collected. The findings were correlated with the overexpression of BIII-tubulin protein measured by immunohistochemistry techniques (IHC) with a purified and monoclonal Ac mouse. Results: The median age and Karnofstky index (KI) were 68 years (range 49-77) and 80% (60-90) respectively. Five patients (15.6%) had received only one anti-hormone treatment, fifteen (46.8), two and twelve (37.5) more than two lines. Twenty patients (62.5) had only one metastatic localization. The median of PSA value before the docetaxel treatment was 302 (4-3745). With a median of eight cycles (3-10) of docetaxel (75mg/m2/ /3s) 41% of patients achieved biochemical response with a median PFS and OS of 4.9 and 19.6 months respectively. Moderate-intense overexpression of BIII-tubulin was identified in five patients (15.6) and minimal or absent in 27 (84.4). In univariate analysis, over-expression was correlated with KI, but not with Gleason score. PSA responses to docetaxel was observed in four patients (80%) with over-expression compared with 20% of those with minimal or absent BIII-tubulin staining. The median PFS and OS for patients with over-expression was 8.6 and 20 months respectively compared to 4.3 and 17 months for those with minimal or absent BIII-tubulin. Conclusions: Over-expression of BIII-tubulin in tumor prostate tissue, applying the present technique is unusual. Its presence appears to be related with higher biochemical response to docetaxel and improvement in PFS and OS. These findings are discordant with those previously published.

5579 Background: Pegylated liposomal doxorubicin (PLD) constitutes the reference treatment for platinum-resistant (PR) ovarian cancer (OC). The combination of gemcitabine (G) + PLD seems to have ad...

17052 Background: Previous comparative studies have shown similar efficacy and less toxicity with either the Gemcitabine(G)/Vinorelbine(V) or Gemcitabine/Docetaxel(D) combination with respect to platinum-based chemotherapies in patients with advanced NSCLC. This trial was designed to test the efficacy and safety of both GV and GD combination in non-selected patients with advanced NSCLC. Methods: Patients (n = 39) with ≤75 years of age, KPS ≥ 60% and adequate haematological, renal and hepatic function were randomly assigned to: G 1250 mg/m2 i.v. d1 and d8 plus either V 25 mg/m2 i.v. d1 and d8 or D 35 mg/m2 i.v. d1 and d8 every 3 weeks. Prophylactic i.v. ranitidine (50 mg), diphenhydramine (25 mg) and dexamethasone (8 mg) were prescribed just prior to the administration of taxane that was given over 30 minutes immediately before gemcitabine. Results: Baseline characteristics were comparable in GV (n = 20) and GD (n = 19) arms: median age (67 years) and KPS (70%), most patients were male (79%), had metastatic disease (85%) and adenocarcinoma histology (55%). Treatment indicated objective response of 7 (35%) versus 6 (31%) patients, median time-to-treatment failure of 120 versus 90 days, and overall survival of 209 versus 177 days in GV and GD arms respectively. The most common non-haematological toxicities were (GV versus GD; No. of patients): grade 2–4 pulmonary toxicity in 1 versus 7 (37%); grade 2–3 diarrhoea in 0 versus 4 (21%) and oedemas 1 versus 3. Grade 2–4 haematological toxicities in 5 versus 2 patients. All side effects were reversible phenomena since resolution was achieved by suspending the treatment and in the case of the pulmonary toxicity, by the prescription of additional corticoids. Conclusion: The combination of Gemcitabine/Docetaxel does not have a favourable safety profile with this schedule of administration, particularly in terms of pulmonary toxicity. Further patients’ enrolment was stopped and the study has been terminated. This kind of toxicity and alternative schedules of GD combination warrant further investigation. No significant financial relationships to disclose.

7121 The combinations of cisplatin (C) with gemcitabine (G) and/or vinorelbine (V) have shown to be effective and safe regimens in the first line treatment of NSCLC. This study has been designed to detect a 25% increase in objective response measured by CT scan with the triplet combination (CGV) with respect to cisplatin/gemcitabine combination (CG) administered as neo-adjuvant therapy in patients with radically-treatable stage III NSCLC. With 80% of power and one-sided 5% significant level, the simple size required to confirm this hypothesis is 75 evaluable patients in each arm of treatment. Patients (pts) ≤ 75 years old, Karnofsky index ≥ 70% and adequate haematological, renal and hepatic function are stratified by stage (IIIA versus IIIB) and randomly assigned to: C 50 mg/m2 i.v. and G 1250 mg/m2 i.v. d1 and d8 alone (CG) or in combination with V 25 mg/m 2 i.v. d1 and d8 (CGV) both regimens every 3 weeks for 3 consecutive cycles followed by definitive local treatment (LT). From December 1999 to December 2005, a hundred and forty-nine pts have been randomised (CG/CGV); median age 58/58; median Karnofsky index 80/80; stage IIIA 24/26; stage IIIB 51/48; squamous 37/39; adenocarcinoma 31/32; anaplastic 7/3. Major haematological toxicities grade 3–4 were (CG/CGV; %); Anaemia (5/5) neutropenia (31/34); thrombocytopenia (4/5). Two pts in CG (2.7%) and 4 in CGV arm (5.5%) developed neutropenic fever. Major non-haematological toxicities grade 2–3 were: N/Vomiting (31/32) and fatigue (12/20). Global recurrences have been registered in 57% and 54% of pts treated with CG and CGV arm respectively. Exclusive local/ distant failure (%) has been 16/23 in CG and 23/18 in CGV arm. Preliminary results show similar high efficacy associated with moderate toxicity in both groups of treatment. The study is continuing. [Table: see text] No significant financial relationships to disclose.

8188 Background: The use of central venous catheters to facilitate drug delivery and supportive treatment in cancer patients (pts) is increasing continuously. Methods: Staff of our department specially trained routinely implant central venous accesses in the office or in the hospitalization yard, under strict aseptic measures without fluoroscopic control or sedation. Results: From Sep 94 to Sep 97, 683 devices (613 port systems [PS] and 70 external catheters [EC]) were implanted in 642 pts, with age 46 yr (14–78) and K.I. 70% (50–100) (mean, range), female 365/male 277. Venous access: right interior jugular 377, left subclavian 205, right subclavian 68, left interior jugular 30, right femoral 3. A thorax X-ray was performed after each procedure and in the first 72 pts prophylactic antibiotics were given. The venous access remained in situ a median of 265 days (1- 2210 +), 120 d (1- 450+) for EC and 327 d (1- 2210+) for PS. Complications occurred in 102 placements (15%): Infections 48 (7%): [30 in EC and 1...