Instituto Nacional Of Cancerologia Incan

Mexico City, Mexico

Instituto Nacional Of Cancerologia Incan

Mexico City, Mexico

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Arrieta O.,Instituto Nacional Of Cancerologia Incan | Nunez-Valencia C.,National Autonomous University of Mexico | Alvarado S.,Sub direccion de Medicina Interna | Flores-Estrada D.,Instituto Nacional Of Cancerologia Incan | And 2 more authors.
Lung Cancer | Year: 2012

Introduction: Lung cancer (LC) is the first cause of cancer-related mortality worldwide and health-related quality of life (HRQL) is a fundamental outcome for evaluating treatment results. Our objective was to validate the Mexican-Spanish versions of the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life QLQ-LC13 disease-specific questionnaire module in Mexican patients with LC; and to explore the possible prognostic role of HRQL data. Methods: Translation procedures followed EORTC guidelines. Both instruments were completed by patients with LC. Tests for reliability and validity were performed. A subset of patients was administered HRQL evaluations before and after chemotherapy. HRQL was associated with prognosis in chemotherapy-naïve patients. The protocol was approved by the Institute's Ethics Committee. Results: One hundred fifty three patients (mean age, 60.3 years; 84 females and 69 males) completed both questionnaires. Compliance rates were high, and the questionnaires were well accepted. Nine of 10 multi-item scales of both questionnaires presented Cronbach's alpha coefficients > 0.7. Multi-trait scaling analysis demonstrated good convergent and discriminant validity. Patients with better Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status reported better functional HRQL scores. Different scales in the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires were accurately related with clinical characteristics. Functional as well as disease-symptom scales improved after chemotherapy, but treatment side-effects scales worsened in test-retest analysis. Better role functioning and absence of thoracic pain scales were associated with longer overall survival (OS) (p= 0.009 and p= 0.035, respectively). Conclusion: The Mexican-Spanish versions of the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires are reliable and valid for HRQL measurement in Mexican patients with LC and can be used in clinical trials. © 2012 Elsevier Ireland Ltd.

Garon E.B.,University of California at Los Angeles | Ciuleanu T.-E.,University of Medicine and Pharmacy, Cluj-Napoca | Arrieta O.,Instituto Nacional Of Cancerologia Incan | Prabhash K.,Tata Memorial Center | And 20 more authors.
The Lancet | Year: 2014

Background Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. We aimed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or placebo as second-line treatment for patients with stage IV non-small-cell-lung cancer (NSCLC) after platinum-based therapy. Methods In this multicentre, double-blind, randomised phase 3 trial (REVEL), we enrolled patients with squamous or non-squamous NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen. Patients were randomly allocated (1:1) with a centralised, interactive voice-response system (stratified by sex, region, performance status, and previous maintenance therapy [yes vs no]) to receive docetaxel 75 mg/m 2 and either ramucirumab (10 mg/kg) or placebo on day 1 of a 21 day cycle until disease progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was overall survival in all patients allocated to treatment. We assessed adverse events according to treatment received. This study is registered with, number NCT01168973. Findings Between Dec 3, 2010, and Jan 24, 2013, we screened 1825 patients, of whom 1253 patients were randomly allocated to treatment. Median overall survival was 10·5 months (IQR 5·1-21·2) for 628 patients allocated ramucirumab plus docetaxel and 9·1 months (4·2-18·0) for 625 patients who received placebo plus docetaxel (hazard ratio 0·86, 95% CI 0·75-0·98; p=0·023). Median progression-free survival was 4·5 months (IQR 2·3-8·3) for the ramucirumab group compared with 3·0 months (1·4-6·9) for the control group (0·76, 0·68-0·86; p<0·0001). We noted treatment-emergent adverse events in 613 (98%) of 627 patients in the ramucirumab safety population and 594 (95%) of 618 patients in the control safety population. The most common grade 3 or worse adverse events were neutropenia (306 patients [49%] in the ramucirumab group vs 246 [40%] in the control group), febrile neutropenia (100 [16%] vs 62 [10%]), fatigue (88 [14%] vs 65 [10%]), leucopenia (86 [14%] vs 77 [12%]), and hypertension (35 [6%] vs 13 [2%]). The numbers of deaths from adverse events (31 [5%] vs 35 [6%]) and grade 3 or worse pulmonary haemorrhage (eight [1%] vs eight [1%]) did not differ between groups. Toxicities were manageable with appropriate dose reductions and supportive care. Interpretation Ramucirumab plus docetaxel improves survival as second-line treatment of patients with stage IV NSCLC. Funding Eli Lilly. © 2014 Elsevier Ltd.

Cornejo-Juarez P.,Instituto Nacional Of Cancerologia Incan | Perez-Jimenez C.,Instituto Nacional Of Cancerologia Incan | Silva-Sanchez J.,Instituto Nacional Of Salud Publica Insp | Velazquez-Acosta C.,Instituto Nacional Of Cancerologia Incan | And 4 more authors.
PLoS ONE | Year: 2012

Introduction: Patients with hematologic malignancies have greater risk-factors for primary bloodstream infections (BSI). Methods: From 2004-2009, we analyzed bacteremia caused by extended-spectrum beta-lactamase Escherichia coli (ESBL-EC) (n = 100) and we compared with bacteremia caused by cephalosporin-susceptible E. coli (n = 100) in patients with hematologic malignancies. Objective: To assess the clinical features, risk factors, and outcome of ESBL-EC BSI in patients with hematologic malignancies, and to study the molecular epidemiology of ESBL-EC isolates. Results: The main diagnosis was acute leukemia in 115 patients (57.5%). Death-related E. coli infection was significantly increased with ESBL-EC (34% vs. control group, 19%; p = 0.03). Treatment for BSI was considered appropriate in 64 patients with ESBL-EC (mean survival, 245±345 days), and in 45 control patients this was 443±613 (p = 0.03). In patients not receiving appropriate antimicrobial treatment, survival was significantly decreased in cases compared with controls (26±122 vs. 276±442; p = 0.001). Fifty six of the ESBL-EC isolates were characterized by molecular analysis: 47 (84%) expressed CTX-M-15, two (3.6%) SHV, and seven (12.5%) did not correspond to either of these two ESBL enzymes. No TLA-1 enzyme was detected. Conclusions: Patients who had been previously hospitalized and who received cephalosporins during the previous month, have an increased risk of ESBL-EC bacteremia. Mortality was significantly increased in patients with ESBL-EC BSI. A polyclonal trend was detected, which reflects non-cross transmission of multiresistant E.coli isolates. © 2012 Cornejo-Juárez et al.

Villarreal-Garza C.,Instituto Nacional Of Cancerologia Incan | De La Mata D.,INCan | Zavala D.G.,National Autonomous University of Mexico | MacEdo-Perez E.O.,Instituto Nacional Of Cancerologia Incan | And 3 more authors.
Clinical Lung Cancer | Year: 2013

Between 30% and 50% of patients with non-small-cell lung cancer (NSCLC) will develop cerebral metastases in the course of their illness. As improvements are made in the local brain treatment, the question arises on how to manage patients with NSCLC who have solely stable brain metastatic disease and if treatment should be considered for the primary lung lesion. The present article will review published series of patients with NSCLC and with brain metastases treated with aggressive thoracic management, with either lung tumor resection or thoracic radiation with or without chemotherapy as definitive treatment. We will also assess which prognostic factors may be useful in the identification of the subset of patients who could benefit from this more aggressive approach. For patients treated with surgical resection for the primary lung tumor, median survival ranged from 19 to 27 months, and the 1-, 2-, and 5-year survival reached 56%-69%, 28%-54%, and 11%-24%, respectively. Patients treated with aggressive radiotherapy with or without chemotherapy, achieved a median survival of 15.5-31.8 months, with a 1-year survival of 50%-71%, and a 2-year survival of 16%-60%. Well-selected patients with NSCLC and with exclusively oligometastatic cerebral disease represent a subgroup of patients with stage IV NSCLC that might achieve long-term survival after treatment directed to the brain and lung tumor lesions. Patients with N0 or N1 disease may be selected for surgical thoracic treatment, whereas those with N2 or N3 disease may benefit from combined chemoradiotherapy in the absence of progression after induction chemotherapy. © 2013 Elsevier Inc. All rights reserved.

Gamboa-Vignolle C.,Instituto Nacional Of Cancerologia Incan | Ferrari-Carballo T.,Instituto Nacional Of Cancerologia Incan | Arrieta O.,Instituto Nacional Of Cancerologia Incan | Mohar A.,National Autonomous University of Mexico
Radiotherapy and Oncology | Year: 2012

Background and purpose: This randomised phase II study evaluated the use of Temozolomide (TMZ) concomitant with 30 Gray (Gy) of Whole-brain irradiation (WBI) for 2 weeks without adjuvant TMZ vs. WBI alone in patients with Brain metastases (BM) from solid tumours. Materials and methods: Fifty-five patients were randomised into the following groups: 28 patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with once-daily 200 mg TMZ on Mondays, Wednesdays, and Fridays, and 300 mg TMZ on Tuesdays and Thursdays (TMZ plus WBI arm). Twenty-seven patients received the same schedule of WBI alone (control arm). Results: The objective response (OR) was 78.6% for the TMZ plus WBI arm, (95% confidence interval [CI], 63.4-93.8%) and 48.1% (29.3-66.9%) for the control arm (p = 0.019). Median Progression-free survival (PFS) of BM was 11.8 months (CI, 4.7-8.9 months) and 5.6 months (4.9-6.2 months) for the TMZ plus WBI and control arms, respectively, (Hazard ratio [HR], 0.24; CI, 0.09-0.65; p = 0.005). Overall survival (OS) of 8.0 Months for the TMZ plus WBI arm and 8.1 months for the control arm, were not significantly different. Conclusion: A daily fixed dose of TMZ during WBI without adjuvant TMZ was well tolerated and significantly improved local control of BM compared with WBI alone. These findings require confirmation in a phase III trial ( number, NCT01015534). © 2011 Elsevier Ireland Ltd. All rights reserved.

Arrieta O.,Instituto Nacional Of Cancerologia Incan | Arrieta O.,National Autonomous University of Mexico | Angulo L.P.,Instituto Nacional Of Cancerologia Incan | Nunez-Valencia C.,Instituto Nacional Of Cancerologia Incan | And 6 more authors.
Annals of Surgical Oncology | Year: 2013

Background: Symptoms of depression and anxiety are common in patients with lung cancer and may produce an impact on both health-related quality of life (HRQL) and survival. The aim of the present study was to evaluate the association of depression and anxiety on HRQL, treatment adherence, and prognosis in patients with non-small cell lung cancer (NSCLC). Methods: This is a prospective study of patients with stage IIIB or IV NSCLC. Depression and anxiety were measured using the hospital anxiety and depression scale, the International Neuropsychiatric Interview, and the HRQL with the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Instruments were applied before treatment and repeated at 3 and 6 months. Lack of treatment adherence was considered as patients who stopped going to their consultation appointments. Results: A total of 82 patients were included. At the initial evaluation, depression and anxiety were found in 32.9 and 34.1 % of patients, respectively. Depression was associated with feminine gender (p = 0.034) and poor performance status (p = 0.048). Depression and anxiety showed an association with HRQL. Patients with depression showed median overall survival of 6.8 months, whereas that for nondepressed patients was 14 months (hazard ratio [HR], 1.9; 95 % confidence interval (95 % CI), 1.03-3.7; p = 0.042). The 58 % of patients with depression had poor treatment adherence versus 42 % of patients without depression (p = 0.004). Conclusions: Depression and anxiety were present in one-third of patients with recently diagnosed NSCLC. Depression and anxiety were associated with decreased HRQL scales, and depression was independently associated with treatment adherence and with poor prognosis. © 2012 Society of Surgical Oncology.

Macedo-Perez E.O.,Instituto Nacional Of Cancerologia Incan | Morales-Oyarvide V.,Instituto Nacional Of Cancerologia Incan | Mendoza-Garcia V.O.,Instituto Nacional Of Cancerologia Incan | Dorantes-Gallareta Y.,Instituto Nacional Of Cancerologia Incan | And 2 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2015

Purpose: Paclitaxel and docetaxel are two taxanes approved for the treatment of non-small-cell lung cancer (NSCLC). However, there is limited evidence regarding the efficacy of docetaxel in NSCLC previously treated with a paclitaxel-platinum doublet (PP). The aim of our study was to evaluate the response to docetaxel in NSCLC patients with prior PP treatment. Methods: Patients with stage IV NSCLC treated with PP that presented disease progression and received docetaxel as second-line treatment were included. Demographics, clinical characteristics, EGFR mutation status, objective response (OR), overall survival (OS), progression-free survival (PFS), and PFS without chemotherapy after first line with PP were analyzed. Results: Sixty-three patients were evaluated. Median age was 58 years, 54 % of patients were women, 53 % were never-smokers, and 39 % had EGFR mutations. OR and median PFS for PP were 36.5 % and 6.7 months, respectively. OR and median PFS for docetaxel were 19 % and 3.8 months, respectively. Patients with EGFR mutations had better response to docetaxel compared with wild-type patients (26 vs. 17 %, p = 0.028). However, only long PFS (>6 months) to first-line PP was independently associated with a higher OR [RR 6.3, 95 % CI (1.03-38.4), p = 0.046], and longer PFS [0.49 (0.25-0.9)] and OS [0.2 (0.06-0.7), p = 0.008] to second-line docetaxel compared with patients with short PFS (≤6 months) to PP. Conclusions: Previous use of PP does not preclude a favorable response to docetaxel in NSCLC. Long PFS with PP may help select NSCLC patients who benefit from second-line docetaxel. © 2014 Springer-Verlag Berlin Heidelberg.

Candelaria M.,Instituto Nacional Of Cancerologia Incan | De La Cruz-Hernandez E.,Instituto Nacional Of Cancerologia Incan | Perez-Cardenas E.,Instituto Nacional Of Cancerologia Incan | Trejo-Becerril C.,Instituto Nacional Of Cancerologia Incan | Gutierrez-Hernandez O.,Instituto Nacional Of Cancerologia Incan
Medical Oncology | Year: 2010

Gemcitabine (2′,2′-difluoro 2′deoxycytidine, dFdC) is an analog of cytosine with distinctive pharmacological properties and a wide antitumor-activity spectrum. The pharmacological characteristics of gemcitabine are unique because two main classes of genes are essential for its antitumor effects: membrane transporter proteincoding genes, whose products are responsible for drug intracellular uptake, as well as enzyme-coding genes, which catalyze its activation and inactivation. The study of the pharmacogenetics and pharmacoepigenetics of these two gene classes is greatly required to optimize the drug's therapeutic use in cancer. This review aims to provide an update of genetic and epigenetic bases that may account for interindividual variation in therapeutic outcome exhibited by gemcitabine. © Humana Press Inc. 2009.

Arrieta O.,Instituto Nacional Of Cancerologia Incan | Blake M.,Instituto Nacional Of Cancerologia Incan | De La Mata-Moya M.D.,Instituto Nacional Of Cancerologia Incan | Corona F.,Instituto Nacional Of Cancerologia Incan | And 4 more authors.
Radiotherapy and Oncology | Year: 2014

Background Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). Methods This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Results Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). Conclusions The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings. © 2014 Elsevier Ireland Ltd. All rights reserved.

Campos-Parra A.D.,Instituto Nacional Of Cancerologia Incan | Aviles A.,Instituto Nacional Of Cancerologia Incan | Contreras-Reyes S.,Instituto Nacional Of Cancerologia Incan | Rojas-Marin C.E.,Instituto Nacional Of Cancerologia Incan | And 3 more authors.
European Respiratory Journal | Year: 2014

Since the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS) reported a new lung adenocarcinoma (ADC) classification, several groups have validated its association with prognosis in early stage disease. To our knowledge, there are no studies in advanced disease. We reviewed 313 patients with invasive lung ADC who were re-classified using the new IASLC/ATS/ERS criteria. Patients received platinum-based chemotherapy. Clinical characteristics, EGFR mutations, response and progression-free survival (PFS) after chemotherapy and overall survival were analysed. ADCs were classified as lepidic 7.4%, acinar 44.7%, papillary 10.1%, micropapillary 3.5% and solid 34.2%. When patterns were lumped into groups, response rates and PFS to platinum-based chemotherapy were better in high-grade ADC (micropapillary, papillary and solid-predominant) versus intermediate-grade ADC (lepidic and acinar-predominant) (36.9% versus 25.4% p=0.034 and 6.4 versus 5.5 months p=0.009, respectively). Overall survival was better in high-grade ADC (25 versus 16.8; p=0.023). Factors associated with better overall survival were Eastern Cooperative Oncology Group (0-1), EGFR mutations and highgrade ADC. Prognostic differences found with the new classification in early disease may not apply to patients with advanced disease. Unlike in early stages, patients with high-grade ADC have longer overall survival compared with intermediate-grade ADC, probably due to a better response to chemotherapy. Copyright © ERS 2014.

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