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[Background The aim of this study was to evaluate the impact of certain single-nucleotide polymorphisms (SNPs) in cabazitaxel activity and tox]icity in patients with metastatic castration-resistant prostate cancer (mCRPC)., [Patients & methods] 56 SNPs in five genes (CYP3A4, CYP3A5, ABCB1, TUBB1 and CYP2C8) were genotyped in 67 mCRPC patients and their correlation with outcomes analyzed., [Results]TUBB1-rs151352 (hazard ratio: 0.52) and CYP2C8-rs1341164 (hazard ratio: 0.53) were associated with better overall survival, and CYP2C8-rs1058932 with biochemical progression (odds ratio: 6.60) in multivariate analysis. ABCB1-rs17327624 correlated with severe toxicity ≥grade 3 (odds ratio: 8.56) and CYP2C8-rs11572093 with asthenia (odds ratio: 8.12)., [Conclusion] Genetic variants in mCRPC patients could explain different outcomes with cabazitaxel. Nonetheless, the small sample size and the high number of SNPs analyzed mean that the results are only hypothesis-generating and require further validation.

Purpose Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. Methods/patients Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. Results 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01–34.2 vs. 27 months, 95% CI 22.6–31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4–37.6 vs 25 months, 95% CI 20.7–29.3; p = 0.821). Serum albumin levels p Conclusions There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.

Glioblastoma is the most common primary brain tumor and the initial treatment with maximal safe resection is not curative. In order to improve the prognosis, surgery is completed with radiotherapy and temozolomide, an oral chemotherapy, but overall survival remains poor. Therefore, new efforts are needed to improve these results. In fact, different systemic treatments have been tested but, nevertheless, few advances have been reached despite the development of large clinical trials. This chapter will review the most important findings, achievements, and main studies in this pathology. Standard of care in newly diagnosed and recurrent glioblastoma will be reassessed with the results of clinical trials with targeted agents and immunotherapy. Ongoing studies are evaluating advanced treatments, with chimeric antigen receptor T-cells, biospecific T-cell antibodies, tumor vaccines, and oncolytic viruses, although results are pending, a wide review of these new-generation agents is important to better understand the advances in glioblastoma in the coming years.

Temozolomide (TMZ), an oral alkylating prodrug which delivers a methyl group to purine bases of DNA (O6-guanine; N7-guanine and N3-adenine), is frequently used together with radiotherapy as part of the first-line treatment of high-grade gliomas. The main advantages are its high oral bioavailability (almost 100% although the concentration found in the cerebrospinal fluid was approximately 20% of the plasma concentration of TMZ), its lipophilic properties, and small size that confer the ability to cross the blood-brain barrier. Furthermore, this agent has demonstrated activity not only in brain tumors but also in a variety of solid tumors. However, conventional therapy using surgery, radiation, and TMZ in glioblastoma results in a median patient survival of 14.6 months. Treatment failure has been associated with tumor drug resistance. This phenomenon has been linked to the expression of O6-methylguanine-DNA methyltransferase, but the mismatch repair system and the presence of cancer stem-like cells in tumors have also been related to TMZ resistance. The understanding of these mechanisms is essential for the development of new therapeutic strategies in the clinical use of TMZ, including the use of nanomaterial delivery systems and the association with other chemotherapy agents. The aim of this review is to summarize the resistance mechanisms of TMZ and the current advances to improve its clinical use.

463 Background: Real-world evidence on la/mUC management in Europe is limited. This study describes patient (pt) characteristics, treatment patterns, survival, and HCRU for pts with la/mUC in Spain. Methods: A retrospective chart review was conducted using electronic medical records from 9 university hospitals in Spain. The study population included all pts aged ≥18 y with a first diagnosis/record of la/mUC from 1/1/2015–12/31/2020 (study period). Date of first la/mUC record/diagnosis during the study period was the index date. Pts with urachus carcinoma or other nonurothelial cancers were excluded. Pt characteristics are described for the full study population. Treatment patterns, survival, and la/mUC-associated HCRU are described for the follow-up cohort: a subset of the study cohort with a first la/mUC diagnosis/record from 1/1/2015–6/30/2020 (ie, to allow for ≥6 mo follow-up). Pts were followed from index date to death, loss to follow-up, or end of study. Median overall survival (OS) and progression-free survival (PFS; evaluated in a real-world setting) were determined using Kaplan–Meier curves. Time to progression, excluding pts who died and were censored at death, was also estimated. HCRU included inpatient admissions, outpatient visits, and emergency visits. Results: Overall, 903 pts were included. Median age at la/mUC diagnosis was 70 y; 79.6% were men. Most (71.0%) had ≥1 comorbidity, most commonly cardiovascular disease (54.2%). Primary tumor sites were the bladder (83.7%), urethra (7.0%), and upper tract (6.6%). De novo la/mUC (41.9%) was the most common initial UC diagnosis. In the follow-up cohort (n = 829), median follow-up was 12.7 mo. Most (84.7% [n = 702]) pts received first-line (1L) systemic treatment; of these, 46.9% (n = 329) received second-line (2L) and 16.6% (n = 116) received third-line (3L) therapy. Chemotherapy was the most common treatment (1L: 77.8% [n = 546]; 2L: 49.8% [n = 164]; 3L: 74.1% [n = 86]), followed by PD-1/L1 inhibitors (1L: 28.3% [n = 199]; 2L: 47.7% [n = 157]; 3L: 19.0% [n = 22]). From index la/mUC diagnosis, estimated median (95% CI) OS was 18.8 (17.5–21.5), PFS was 9.9 (8.9–10.5), and time to progression was 12.7 (11.3–14.6) mo. From the start of 1L, 2L and 3L therapy, estimated median (95% CI) OS were 16.9 (14.3–18.9), 11.6 (9.6–14.3), and 9.9 (7.9–12.6) mo. For HCRU, 71.8% (n = 595) of pts had ≥1 outpatient visit (mean: 2.2/mo), 56.6% (n = 469) had ≥1 inpatient admission (0.4/mo; median duration: 8.0 d), and 56.5% (n = 468) had ≥1 emergency visit (0.4/mo). Conclusions: This retrospective study of university hospital data describes pt characteristics and real-world treatment patterns, survival, and HCRU for pts with la/mUC in Spain. Advances in immunotherapy are shifting the treatment landscape for targeted groups of pts with la/mUC, but a need remains for innovative treatments that could improve pt outcomes.

espanolLas instituciones del Espacio Iberoamericano del Conocimiento (EIC) colaboran en proyectos educativos. Siendo la competencia comunicativa imprescindible para el desarrollo profesional y la colaboracion del propio EIC. Este trabajo analiza los resultados de un proyecto educativo de colaboracion entre ocho universidades y cinco paises Iberoamericanos sobre la construccion de una rubrica comun validada con Delphi para evaluar las competencias orales en la exposicion de proyectos por los estudiantes. La rubrica se aplico en tres grupos de estudiantes de tres instituciones y paises distintos (Cuba, Ecuador y Espana), con modalidades de evaluacion formativa (docente, autoevaluacion y pares), analizando 788 evaluaciones totales (90 docentes, 61 autoevaluaciones y 637 pares). Los resultados confirman un “alfa de Cronbach” (.934) para las 22 variables analizadas. Con la prueba de Post-Hoc de Tukey en todos los items las evaluaciones de pares obtienen peores resultados que evaluacion docente, mientras que las autoevaluaciones son mejores. La opinion de los estudiantes con un instrumento validado de satisfaccion obteniendo una propuesta significativa de reedicion de la rubrica. El articulo ofrece como producto una rubrica base validada y experimentada exitosamente en contextos geograficamente diferenciados del EIC EnglishThe institutions of the Ibero-American Knowledge Space (EIC) collaborate in educational projects. Communication skills are essential for the professional development and collaboration of the EIC itself. This paper analyzes the results of a collaborative educational project between eight universities and five Ibero-American countries on the construction of a common rubric validated with Delphi to assess oral competences in the presentation of projects by students. The rubric was applied to three groups of students from three different institutions and countries (Cuba, Ecuador and Spain), with formative evaluation modalities (teacher, self-evaluation and peers), analyzing 788 total evaluations (90 teachers, 61 self-evaluations and 637 peers). The results confirm a "Cronbach's alpha" (.934) for the 22 variables analysed. With Tukey's Post-Hoc test in all items, the peer evaluations are worsethan the teacher evaluations, while the self-evaluations are better. The students' opinion with a validated satisfaction instrument obtaining a significant proposal to reissue the rubric. The article offers as a product abase rubric validated and successfully experienced in geographically differentiated contexts of the EIC

Purpose: Docetaxel improves survival in patients with metastatic prostate cancer. This randomized phase 2 trial aimed to assess the activity of weekly docetaxel with radiation therapy (RT) plus androgen deprivation in patients with high-risk localized prostate cancer. The study examined the benefit of 9 weekly docetaxel administrations to RT plus 3 years of luteinizing hormone-releasing hormone analogues. Methods and Materials: A total of 132 patients were recruited for the study. Patients' characteristics included T3-T4 stage (81.1%), Gleason score >= 8 (77.3%), prostate-specific antigen level >20 ng/mL (28.9%), and pN+ (18.2%). All patients included in the trial received either the standard-of-care control arm with luteinizing hormone-releasing hormone analogues plus RT (arm A) or the experimental arm (RT + 9 weekly cycles of docetaxel + 3 years of androgen deprivation therapy, arm B). The primary objective was to achieve a high percentage of patients who were free of biochemical recurrence within 5 years of randomization. Secondary endpoints included biochemical recurrence-free survival (BRFS), progression-free survival (PFS), overall survival (OS), clinical response rate, biochemical response rate, and toxicity. Results: No difference between the arms of the study was found in biochemical recurrence (93.4% at 60 months for arm A vs 85.3% for arm B; P = .3297). PFS at 60 months was 93.4% and 83.7% in arms A and B, respectively (P = .2532). Five-year survival was 93.3% (95% confidence interval, 83.1-97.45) in arm A versus 93.6% (83.8-97.55) in arm B; median PFS and OS have not been reached. Prostate-specific antigen level

Bladder cancer is the fourth most common cancer in men and the ninth most common in women in the Western world. The management of bladder carcinoma requires a multidisciplinary approach. Optimal treatment depends on several factors, including histology, stage, patient status, and possible comorbidities. Here we review recent findings on the treatment of muscle-invasive bladder carcinoma, advanced urothelial carcinoma, upper tract urothelial carcinoma, non-urothelial carcinoma, and urologic complications arising from the disease or treatment. In addition, we present the recommendations of the Spanish Oncology Genitourinary Group for the treatment of these diseases, based on a focused analysis of clinical management and the potential of current research, including recent findings on the potential benefit of immunotherapy. In recent years, whole-genome approaches have provided new predictive biomarkers and promising molecular targets that could lead to precision medicine in bladder cancer. Moreover, the involvement of other specialists in addition to urologists will ensure not only appropriate therapeutic decisions but also adequate follow-up for response evaluation and management of complications. It is crucial, however, to apply recent molecular findings and implement clinical guidelines as soon as possible in order to maximize therapeutic gains and improve patient prognosis.

Review of S.J. Deeley's book on learning and service methodology in higher education. Compulsory Secondary and Baccalaureate, and Vocational Training from anywhere in Spain, and from those countries whose educational systems are designed by competences.

Aim: We aimed to identify SNPs associated with cabazitaxel toxicity and response within a Phase II clinical trial using this compound in advanced transitional cell carcinoma after progression to a platinum-based regimen. Patients & methods: Eleven SNPs in CYP3A4, CYP3A5, CYP2C8, ABCB1 and TUBB1 were genotyped in 45 patients. Results: CYP3A5 rs776746 A allele was associated with protection against gastrointestinal toxicity (odds ratio: 0.06, 95% CI: 0.007–0.63, p = 0.018) and with reduced progression-free survival (hazard ratio: 5.1, 95% CI: 1.7–15.1, p = 0.0038, multivariable analysis). ABCB1 SNPs were associated with total number of grade 3–4 toxicity events (p-values of 0.009, 0.041 and 0.043, respectively). Conclusion: Polymorphisms in CYP3A5 and ABCB1 may define a subset of patients with different cabazitaxel toxicity and efficacy and therefore could be used as markers for treatment optimization.

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p

Background Abiraterone (Abi), enzalutamide (Enz) and docetaxel (Doc) are all approved first-line (1L) treatment options for mCRPC. However, the optimal treatment sequence has not been established yet. In the present analysis, we explored the outcomes of pts treated with 1L Doc or Abi/Enz in the prospective PROREPAIR-B cohort study (NCT03075735). Methods We assessed the impact of 1L treatment options (Doc vs Abi/Enz) on progression-free survival to 1L therapy (PFS) and overall survival (OS). Uni- (UV) and multivariable (MV) Cox-regression models were used. MV model covariates included age (≥75 years), local therapy, Gleason Score, visceral metastases, metastases at diagnosis, phosphatase alkaline (ALP) (≥ULN), lactate dehydrogenase (LDH) (≥ULN), haemoglobin (Hb) (≤LNL), albumin (≤LNL) and ECOG performance status. Results Of 419 pts enrolled in the study, 406 received 1L Doc (n = 188) or Abi/Enz (n = 218). Overall, pts receiving Doc were younger (p = 0.002), had higher rates of visceral metastases (17.6% vs 8.7%, p = 0.008), ALP (52.1% vs 40.4%, p = 0.018), LDH (48.1% vs 31.2%, p Conclusions Pts treated with 1L Doc had worse baseline prognostic features. Despite a longer PFS was observed in pts treated with 1L Abi/Enz vs Doc, no difference in OS was found between the treatment sequences. Similar results were observed in the elderly population. Biomarker-driven pts selection is needed to identify the optimal sequence. Clinical trial identification NCT03075735. Legal entity responsible for the study Centro Nacional de Investigaciones Oncologicas (CNIO). Funding Unrestricted grant from Fundacion Cris Contra el Cancer; three investigator awards from the Prostate Cancer Foundation (C.C.P. [2013], D.O. [2014], and E.C. [2017]); and three grants from Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III (No. PI13/01287 and PI16/01565 to D.O. and No. PI15/01471 to P.L.). During the conduct of this study, E.C., D.O., P.N., and L.M-P. were supported by grants from Ministerio de Economia, Industria y Competitividad (No. JCI-2014-19129 [E.C.], No. RYC-2015-18625 [D.O.], No. SVP-2013-067937 [P.N.], No. SVP-2014-068895 [L.M.]); D.O. was also funded by a Return fellowship from Fundacion Cientifica de la Asociacion Espanola Contra el Cancer, 2012-2015; N.R.L. and R.L., by grants from Instituto de Salud Carlos III (No. CM14-00200 to N.R.L. and No. CM17-00221 [R.L.]); and Y.C., by a grant from Ministerio de Educacion, Cultura y Deportes (No. FPU15/05126). C.C.P. was supported by a congressional-designated medical research program award (No. CMRP-PC131820). Disclosure C. Cattrini: Travel / Accommodation / Expenses: Novartis, Ipsen. N. Romero Laorden: Honoraria (self): MSD, Sanofi-Aventis, Astellas, Janssen-Cilag; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, PharmaMar; Research grant / Funding (institution): Bayer, Astellas, Janssen, Sanofi. E. Castro: Honoraria (self): Astellas Pharma, Janssen-Cilag, AstraZeneca, Bayer, Pfizer; Advisory / Consultancy: Bayer, Janssen-Cilag; Research grant / Funding (institution): Janssen-Cilag, AstraZeneca, Bayer; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, Astellas Pharma. I. Garcia-Carbonero: Advisory / Consultancy: Janssen Oncology, Astellas Pharma, Bayer, Sanofi; Travel / Accommodation / Expenses: Astellas Pharma, Janssen, Sanofi, Bayer. J.M. Piulats: Advisory / Consultancy: Janssen Oncology, Astellas Pharma, VCN Biosciences, Clovis Oncology, Roche, Genentech, Bristol-Myers Squibb, Merck Sharp & Dohme; Research grant / Funding (institution): Bristol-Myers Squibb, AstraZeneca, MedImmune, Merck Sharp & Dohme, Pfizer, EMD Serono, Incyte, Janssen Oncology; Travel / Accommodation / Expenses: Janssen Oncology, Roche, Bristol-Myers Squibb. J. Puente: Advisory / Consultancy: Pfizer, Astellas Pharma, Janssen-Cilag, Merck Sharp & Dohme, Bayer, Roche, Bristol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Ipsen, Eisai, EUSA Pharma, Sanofi; Speaker Bureau / Expert testimony: Pierre Fabre, Celgene, Kiowa, Novartis, Lilly; Research grant / Funding (institution): Astellas Pharma, Pfizer; Research grant / Funding (institution): Pfizer, Roche, Janssen-Cilag. B. P. Valderrama: Honoraria (self): Pierre Fabre, Astellas Pharma, Novartis, Bristol-Myers Squibb, Ipsen; Advisory / Consultancy: Astellas Pharma, Novartis, Pfizer, Pierre Fabre, Bayer, Sanofi, Bristol-Myers Squibb, Roche, Ipsen; Travel / Accommodation / Expenses: Janssen-Cilag, Bristol-Myers Squibb. E. Gonzalez Billalabeitia: Travel / Accommodation / Expenses: Bristol-Myers Squibb, Pfizer, Janssen-Cilag, Astellas Pharma, Sanofi. R. Morales Barrera: Honoraria (self): MSD, Sanofi, AstraZeneca, Asofarma, Johnson and Johnson, Roche/Genentech; Advisory / Consultancy: MSD, Sanofi, AstraZeneca, Asofarma, Johnson and Johnson, Roche/Genentech; Speaker Bureau / Expert testimony: MSD. Sanofi, AstraZeneca, Asofarma, Johnson and Johnson; Research grant / Funding (institution): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma., AstraZeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim Espana, S.A., Bristol-Myers Squibb Intern; Travel / Accommodation / Expenses: MSD, Roche/Genentech, Lilly, Clovis Oncology, Bayer, Johnson and Johnson, Astellas Pharma, AstraZeneca. R. Lozano Mejorada: Honoraria (self): Roche, Janssen-Cilag, Bayer; Research grant / Funding (institution): Bayer, Janssen-Cilag; Travel / Accommodation / Expenses: Roche, Janssen-Cilag, Astellas Pharma. R. Luque: Honoraria (self), Travel / Accommodation / Expenses: Janssen-Cilag, Sanofi Aventis, Astellas Medivation, Roche, Novartis, Pfizer, Bristol-Myers Squibb, EUSA Pharma. E. Martinez Ortega: Honoraria (self), Travel / Accommodation / Expenses: Sanofi Aventis, Roche, Pfizer Bristol Mayers Squibb, EUSA Pharma and IPSEN. J.A. Arranz Arija: Honoraria (self): Novartis MSD Oncology Janssen-Cilag EUSA Pharma Astellas Pharma Bristol-Myers Squibb; Advisory / Consultancy: Pfizer Astellas Pharma Janssen-Cilag Novartis Bayer Ipsen MSD Oncology Bristol-Myers Squibb EUSA Pharma; Research grant / Funding (institution): Novartis Pierre Fabre Bristol-Myers Squibb; Travel / Accommodation / Expenses: Bristol-Myers Squibb Janssen-Cilag MSD Oncology Pfizer. E. Gallardo Diaz: Honoraria (self): Astellas Pharma, Roche, Bristol-Myers Squibb, Novartis; Advisory / Consultancy: Pfizer, Bayer Schering Pharma, Janssen Oncology, Astellas Pharma, Roche, Bristol-Myers Squibb, Sanofi, Ipsen, Eisai, Rovi, Daiichi Sankyo, EUSA Pharma; Speaker Bureau / Expert testimony: Rovi, LEO Pharma, Menarini, Bristol-Myers Squibb, Ipsen, Astellas Pharma, Roche, Daiichi Sankyo; Travel / Accommodation / Expenses: Pfizer, Astellas Pharma, Pierre Fabre, Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Janssen, Roche. E. Almagro Casado: Speaker Bureau / Expert testimony: MSD; Travel / Accommodation / Expenses: Bristol-Myers Squibb. M.J. Mendez Vidal: Advisory / Consultancy: Janssen-Cilag, Pfizer, Astellas Pharma, Sanofi, Bayer, Bristol-Myers Squibb, Novartis, Roche; Travel / Accommodation / Expenses: Janssen-Cilag, Pfizer, Astellas Pharma, Bristol-Myers Squibb. D. Olmos Hidalgo: Speaker Bureau / Expert testimony: Astellas, Bayer, Janssen, Sanofi; Advisory / Consultancy: Astellas, AstraZeneca, Bayer, Genentech, Janssen, Clovis; Research grant / Funding (institution): Astellas, AstraZeneca, Bayer, Genentech/Roche, Janssen (Incl.Aragon), Medivation/Pfizer, Tokai, MSD, GSK; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Ipsen. D. Lorente: Honoraria (self): Janssen-Cilag, Bayer, Astellas Pharma, Sanofi; Advisory / Consultancy: Janssen-Cilag, Bayer, Sanofi; Travel / Accommodation / Expenses: Sanofi, Astellas, Janssen-Cilag, Celgene. All other authors have declared no conflicts of interest.

The follow-up of treated low-grade glioma (LGG) requires the evaluation of subtle clinical changes and MRI results. When the result is inconclusive, additional procedures are required to assist decision-making, such as the use of advanced MRI (aMRI) sequences and nuclear medicine scans (SPECT and PET). The aim of this study was to determine whether incorporating 18F-fluorocholine PET/CT in the follow-up protocol for treated LGG improves diagnostic accuracy and clinical utility. This was a prospective case-series study in patients with treated LGG during standard follow-up with indeterminate clinical and/or radiological findings of tumour activity. All patients underwent clinical evaluation, aMRI, 201Tl-SPECT and 18F-fluorocholine PET/CT. Images were interpreted by visual evaluation complemented with semiquantitative analysis. Between January 2012 and December 2013, 18 patients were included in this study. The final diagnosis was established by histology (five surgical specimens, one biopsy specimen) or by consensus of the Neuro-Oncology Group (11 patients) after a follow-up of >6 months (mean 14.9 ± 2.72 months). The global diagnostic accuracies were 90.9 % for aMRI (38.8 % inconclusive), 69.2 % for 201Tl-SPECT (11.1 % inconclusive), and 100 % for 18F-fluorocholine PET/CT. 201Tl-SPECT led correctly to a change in the initial approach in 38.9 % of patients but might have led to error in 27.8 %. The use of 18F-fluorocholine PET/CT alone rather than 201Tl-SPECT led correctly to a change in the approach suggested by routine follow-up in 72.2 % of patients and endorsed the approach in the remaining 27.8 %. Our results support the need to complement structural MRI with aMRI and nuclear medicine procedures in selected patients. 18F-Fluorocholine PET/CT can be useful in the individualized management of patients with treated LGG with uncertain clinical and/or radiological evidence of tumour activity.

The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects. Colloidal carriers based on biodegradable poly(butylcyanoacrylate) nanoparticles (PBCA NPs) may enhance DOX antitumor activity against breast cancer cells, thus allowing a reduction of the effective dose required for antitumor activity and consequently the level of associated toxicity. DOX loading onto PBCA NPs was investigated in this work via both drug entrapment and surface adsorption. Cytotoxicity assays with DOX-loaded NPs were performed in vitro using breast tumor cell lines (MCF-7 human and E0771 mouse cancer cells), and in vivo evaluating antitumor activity in immunocompetent C57BL/6 mice. The entrapment method yielded greater drug loading values and a controlled drug release profile. Neither in vitro nor in vivo cytotoxicity was observed for blank NPs. The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX. Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment. These results suggest that DOX-loaded PBCA NPs have great potential for improving the efficacy of DOX therapy against advanced breast cancers., This investigation was funded by FEDER, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III (FIS) through projects Nos PI11/01862 and PI11/02571, and by the Consejería de Salud de la Junta de Andalucía through project No PI-0338. The authors wish to express their gratitude to G Ortiz Ferron (CIC, University of Granada, Spain) for his skillful assistance with cytometry experiments.

Background Cabazitaxel is used in the treatment of metastatic prostate cancer. It is not a substrate of P-glycoprotein, which is involved in cellular detoxification of chemotherapeutic agents and in the expulsion of drugs at blood-brain barrier. Our objectives are to test Cabazitaxel in vitro in malignant neural cell lines such as glioblastoma, anaplastic glioma and neuroblastoma, and to find any predictor of response that allows us to select potential responder patients in glioblastoma multiforme and other neural tumors. Methods Cell lines A172 (glioblastoma, p53 wild type), LN229 (glioblastoma, p53 mutated), SF268 (anaplastic glioma, p53 mutated) and SK-N-SH (neuroblastoma, p53 wild type) were cultured in 48-well plates and increasing doses of Cabazitaxel were tested (0.1, 0.5, 1, 5, 10, 25, 50, 100μM). After 48hours of treatment, the proliferation values were studied by spectrophotometric assays. Also, gene expression studies of the MMR complex (miss-match repair) were performed by RT-qPCR for the primers of MLH1, MSH2, MSH3, MSH6, PMS2 genes. We also analyzed the expression of CD133 marker by RT-qPCR assays. A PCR study with Bisulfite kit was carried out to detect the promoter methylation of MGMT. Results IC50 values at 48hours were 13.76μm in SF268, 6.77μm in SK-N-SH, 2.88μm in LN 229 and 1.34 in A172. The expression values of MMR complex proteins were significantly higher in line A172 (relative value 1), followed by line LN229 (0.25) and negative in lines SK-N-SH and SF268. The methylation of MGMT promoter was positive in lines A172 and LN229. Finally, the expression of CD133 was higher in A172 (0.6), followed by LN229 (0.4), SK-N-SH (0.2) and SF268 (0). Pearson correlation coefficient for the relationship between CD133 expression and IC50 values is -0.96. Conclusions 1. Glioblastoma, anaplastic glioma and neuroblastoma cell lines have a high sensitivity to Cabazitaxel in vitro. 2. Cell lines with MGMT methylation and MMR expression (A172 and LN 229) are the most sensitive. Of them, line A172 presents a p53 wild type, and therefore, a greater sensitivity to Cabazitaxel. 3. The expression of CD133 correlates inversely with the values of IC50 to Cabazitaxel, and may also be a predictor of response. Legal entity responsible for the study UGR. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

5053 Background: Abiraterone (Abi), enzalutamide (Enza) and docetaxel (Doc) are all valid first-line (1L) mCRPC treatment options. SIOG guidelines (Droz, Eur Urol 2017) recommend that fit elderly pts should receive the same treatment as younger patients. Evidence of the optimal treatment sequence in this patient subpopulation is lacking. Methods: We evaluated the outcome of elderly (≥ 75 years [yrs]) pts treated in the prospective PROREPAIR-B cohort study (NCT03075735). We assessed the impact of 1L treatment option (Doc vs Abi/Enza) on overall survival (OS) and progression-free survival (PFS) to 1L-therapy following PCWG2criteria. Uni- (UV) and multivariable (MV) cox-regression models were used. MV model covariates included local therapy, Gleason Score, stage IV at diagnosis, visceral metastases, ALP (≥ULN), LDH (≥ULN), haemoglobin (Hb; ≤LNL), albumin (≤LNL) and ECOG PS. Results: 419 pts were included in the study. Of these, 137 (32,7%) had age ≥ 75 yrs. 48 (35%) received docetaxel and 88 (64.2%) had Abi/Enza as first-line therapy. Of the 121 pts that progressed on 1L-therapy, 30 (24.8%) did not receive 2L therapy. Choice of 2L-therapy was: Doc in 37 (30,6%), Abi/Enza in 38 (31.4%), Cabazitaxel in 9 (7.4%) and Radium-223 in 7 (5.8%) pts. Pts treated with 1L-Doc had higher rates of visceral metastases (22.9% vs 5.7%; p=0.003), high ALP (68.8% vs 43.2%; p=0.004) and low Hb (12.5% vs 3.4%). PFS to 1L-therapy was longer for Abi/Enza than for Doc treated pts (9.6 vs 8.3m; HR: 0.52; p=0.001). The pattern of disease progression (PSA, radiographic, clinical) was similar in Doce and Abi/Enza treated pts. No difference between pts treated with initial Abi/Enza vs Doc was observed in OS (28.2 vs 24.8m; HR:1.18; p=0.474). No significant OS differences were observed in the MV model. Conclusions: No differences in OS were observed between treatment sequences starting with Doc vs Abi/Enza in pts ≥ 75 yrs. Pts treated with 1L-Doc had worse baseline prognostic features. Age should not be considered as a factor for treatment choice in elderly mCRPC pts based on treatment outcome.

264 Background: Abiraterone (Abi), enzalutamide (Enza) and docetaxel (Doc) are all valid first-line (1L) mCRPC treatment options. Evidence suggests a degree of cross-resistance between agents, which may impact the efficacy of subsequent lines of therapy. Evidence on the optimal treatment sequence is lacking. Methods: We evaluated the outcome of patients (pts) treated with 1L Doc, Abi or Enza in the prospective PROREPAIR-B cohort study. We assessed the impact of 1L treatment option (Doc vs Abi/Enza) on overall survival (OS), progression-free survival (PFS) to 1L-therapy (PCWG2) and PFS2 (time from initiation of 1L-therapy to progression on second-line [2L] therapy). Uni- (UV) and multivariable (MV) cox-regression models were used. MV model covariates included age (≥75 years), local therapy, Gleason Score, metastases at diagnosis, visceral metastases, ALP (≥ULN), LDH (≥ULN), haemoglobin (≤LNL), albumin (≤LNL) and ECOG PS. Results: 406 pts received 1L-Doce (N=188) or Abi/Enza (N=218). Pts receiving Doc were younger (p=0.002), had higher rates of visceral metastases (17.6 vs 8.7%; p=0.008), ALP (52.1% vs 40.4%; p=0.018), LDH (48.1% vs 31.2%; p

Carboplatin-paclitaxel is a reference regimen in the treatment of locally advanced or disseminated non-small cell lung cancer (NSCLC). This paper discusses the multidrug resistance developed with this drug combination, which is one of the major obstacles to successful treatment. In order to understand and overcome the drug resistance pattern of NSCLC after carboplatin plus paclitaxel exposure, levels of mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 3 (MRP3) were investigated in primary NSCLC cell lines (A-549 and A-427) and a metastasis-derived NSCLC cell line (NODO). Our results showed that exposure of the three NSCLC lines to plasma concentrations of paclitaxel (5 μM) produced an increase in MDR1 expression, while MRP3 showed no alteration in expression. By contrast, the same cells exposed to carboplatin plasma concentrations (30 μM) showed overexpression of MRP3. In these cells, MDR1 showed no expression changes. Interestingly, the combination of both paclitaxel and carboplatin caused increased expression of the MDR1 drug resistance gene rather than the individual treatments. These results suggest that carboplatin and paclitaxel may induce drug resistance mediated by MDR1 and MRP3, which may be enhanced by the simultaneous use of both drugs.

Multidrug resistance is one of the major obstacles to the successful treatment of non-small cell lung cancer (NSCLC). An ability to identify molecular markers of drug resistance in peripheral blood cells in order to better target treatment would therefore be extremely useful in selecting therapy protocols for patients. The aim of the present study was to evaluate whether expression of resistance genes (MDR1, MRP3 and LRP) can predict clinical outcome in NSCLC patients treated with paclitaxel and carboplatin.Peripheral blood samples were obtained from lung cancer patients before and after chemotherapy and expression of the resistance gene in polymononuclear cells was detected by real-time reverse-transcription polymerase chain reaction. The results were correlated with treatment response and overall survival, which was calculated according to the Kaplan-Meier method.MDR1 expression levels in PMNs rose rapidly within 24 h post-administration of paclitaxel and carboplatin, whereas MRP and LRP expression levels remained unchanged. However, no significant correlation was observed between MDR1 expression and the patients' survival or treatment response.Modulation of MDR1 gene expression in PMNs after lung cancer treatment with paclitaxel and carboplatin cannot be used as a prognosis marker in these patients.

Prostate tumors are the most frequent malignant cancer among men. In recent years, we have seen a significant progress in the knowledge of the carcinogenesis of prostate cancer, leading to the development of effective drugs in this scenario. Prostate cancer patients had no effective therapeutic alternatives after docetaxel failure, limiting their survival rates. However, new drugs have markedly improved this. Cabazitaxel, a new generation taxane, has shown improved patient survival, despite the disease progression seen after docetaxel treatment. Herein, we present the case of a prostate cancer patient with poor prognosis and lung metastases in < 6 months postdocetaxel treatment. The patient was treated with cabazitaxel, achieving a long and maintained response. Later, on developing a new progressive disease, the patient was retreated with cabazitaxel, achieving a partial response and obtaining a widespread survival and clinical benefit. We currently have no predictive response factors to establish the most appropriate therapeutic sequence. Close monitoring of these patients is of paramount importance to detect early disease progression and try a new line of treatment, while the patient still has the chance to respond.

The follow-up of treated low-grade glioma (LGG) requires the evaluation of subtle clinical changes and MRI results. When the result is inconclusive, additional procedures are required to assist decision-making, such as the use of advanced MRI (aMRI) sequences and nuclear medicine scans (SPECT and PET). The aim of this study was to determine whether incorporating (18)F-fluorocholine PET/CT in the follow-up protocol for treated LGG improves diagnostic accuracy and clinical utility.This was a prospective case-series study in patients with treated LGG during standard follow-up with indeterminate clinical and/or radiological findings of tumour activity. All patients underwent clinical evaluation, aMRI, (201)Tl-SPECT and (18)F-fluorocholine PET/CT. Images were interpreted by visual evaluation complemented with semiquantitative analysis.Between January 2012 and December 2013, 18 patients were included in this study. The final diagnosis was established by histology (five surgical specimens, one biopsy specimen) or by consensus of the Neuro-Oncology Group (11 patients) after a follow-up of6 months (mean 14.9 ± 2.72 months). The global diagnostic accuracies were 90.9% for aMRI (38.8% inconclusive), 69.2 % for (201)Tl-SPECT (11.1% inconclusive), and 100% for (18)F-fluorocholine PET/CT. (201)Tl-SPECT led correctly to a change in the initial approach in 38.9% of patients but might have led to error in 27.8%. The use of (18)F-fluorocholine PET/CT alone rather than (201)Tl-SPECT led correctly to a change in the approach suggested by routine follow-up in 72.2% of patients and endorsed the approach in the remaining 27.8%.Our results support the need to complement structural MRI with aMRI and nuclear medicine procedures in selected patients. (18)F-Fluorocholine PET/CT can be useful in the individualized management of patients with treated LGG with uncertain clinical and/or radiological evidence of tumour activity.

[Abstract] BACKGROUND: Based on the TROPIC study results, cabazitaxel was approved for the management of metastatic castration-resistant prostate cancer (mCRPC) progressing on or after docetaxel. METHODS: This multi-centre program provided early access to cabazitaxel to patients with mCRPC before its commercialization. Safety data from 153 Spanish patients receiving cabazitaxel 25 mg/m(2) i.v. Q3W, plus oral prednisone/prednisolone 10 mg daily, are reported. RESULTS: Median age of patients was 70 years (26.8% ≥ 75 years), 94.1 and 26.8% had bone and visceral metastasis, respectively. Most had an Eastern Cooperative Oncology Group ≤ 1 (88.9%) and had received a median of 8.0 cycles of last docetaxel treatment. The median of cabazitaxel cycles and cumulative dose were 6.0 (Interquartile range [IQR]: 4.0; 8.0) and 148.9 (IQR: 98.2; 201.4) mg/m(2), respectively. Adverse events (AEs) possibly related to cabazitaxel occurred in 143 (93.5%) patients. The most frequent grade ≥ 3 AEs were neutropenia (n = 25, 16.3%) and asthenia (n = 17, 11.1%). Febrile neutropenia and grade ≥ 3 diarrhea occurred in 5.2% of the patients each. There were five (3.3%) possibly treatment-related deaths, mainly infection-related. G-CSFs were used in 114 (74.5%) patients, generally as prophylaxis (n = 107; 69.9%). Grade ≥ 3 peripheral neuropathy and nail disorders were uncommon. CONCLUSIONS: Cabazitaxel administration, in a real-world setting, is tolerated by Spanish patients with mCRPC, and the AEs are manageable.

229 Background: Novel agents, such as abiraterone (A), cabazitaxel (CZ), and enzalutamide are currently available for the treatment of docetaxel (D)-treated metastatic castration resistant prostate cancer (mCRPC). The sequencing approach following D progression is still unknown. We now explore which factors are driving sequencing decisions in routine clinical practice in Spain. Methods: A prospective multicenter national observational descriptive study collecting data of 2nd line (L) treatments in mCRPC patients to analyze responses and progression to 1stL D. Results: 149 patients have been recruited from July 2013 to January 2015. Median age was 72 (48-89). Median D cycles was 6 (1-24), and median dose: 75 mg/m2 (30-75). 24 patients (16%) required dose reduction. The reasons for D ending were treatment completion (40%, n = 60), toxicity (15.3%, n = 23), progression (radiological, biochemical, clinical; 42%, n = 63), or others (2.7%, n = 4). 67% (n = 100) of the patients received A, 25% (n = 44) CZ, and 8% (n = 5) other treatments as 2ndL. From those who completed or progressed to D (n = 123), 2ndL initiation was mainly determined by two progression criteria (2C; biological and radiological), followed by one progression criteria (1C). This was independent of the 2ndL treatment chosen, and it was observed in similar ratios in both A (2C: 50%, n = 39; 1C: 37.2%, n = 29) and CZ (2C: 62.5%, n = 25; 1C: 27.5%, n = 11). Nevertheless, A was predominantly given when patients progressed after D ending, whereas CZ was mostly given when progressing during D (Table 1). Conclusions: A is the 2ndL treatment of choice in routine clinical practice in Spain, independent of the type and time of progression. CZ is preferentially used in patients progressing during D treatment. [Table: see text]

e15537 Background: No standard regimen exists for second line treatment of mTCC patients. Taxanes have shown some activity in this setting. Cbz, is a novel semi-synthetic taxane never tested before...

e13056 Background: VTE is a common complication in HGG; however, it´s incidence remain uncertain. KS is the only validated predictive model to gauge cancer patient´s cancer risk for developing VTE....

e15597 Background: The IMRCC prognostic model for mRCC treated with VEGF-targeted agents (Heng, JCO '09) has been externally validated (Heng, Lancet Oncol '13), however, pt treated with Pz were not...

4525 Background: Treatment of mTCC progressing to cisplatin is an unmet need. Prognostic factors (PF) for worse overall survival (OS) are ECOG >0, Hb

15 Background: Docetaxel improves survival in patients (pts) with metastatic hormonosensitive prostate cancer (PC) and castration-resistant prostate cancer. The objective of this phase IIb trial was to assess the activity of low dose docetaxel concurrent with radiotherapy plus standard hormonal treatment in pts with high risk localized CaP. Methods: High-risk localized CaP was defined by ≥ 1 of the following criteria: T3-T4, Gleason score (GS) ≥ 8, PSA > 20 ng/mL, pN+. Pts were randomly assigned to either arm A (LH-RH analogs every 3 months for 3 years and radiotherapy 73.8 Gy [1.8 Gy x 41 fractions] or 74 Gy [2Gy x 37 fractions]) or arm B (LH-RH analogs every 3 months for 3 years, radiotherapy and concurrent weekly docetaxel at 20 mg/m2 for 9 weeks). Chemotherapy was started one week before of radiotherapy. Primary endpoint was PSA relapse according to the Phoenix definition. The planned number of pts was 130 to detect a 15% difference with a power of 80% and an alpha of 0.05 (two-sided). Results: From 12/2008 to 9/2012, 130 pts were accrued (Arm A: 64, Arm B: 66). Median age was 68 years (61-73). Patients had T3-T4 (82.6%), GS ≥ 8 (76.3%), PSA > 20 ng/mL (26.9%) and pN+ (18.9%). All characteristics were well-balanced between arms. Median dose of radiotherapy was 74 Gy (72–74.8) in arm A, and 73.8 Gy ( 72-75.6) in arm B. 75.7% of pts received the planned 9 treatments of docetaxel and median number of cycles delivered per patient was 9. After a median follow-up of 29.6 months (9.6-40.2), most common grade 1/2 toxicities (arm A and arm B) were: cystitis ( 12.5% vs 8.3%), diarrhea (35.9% vs 70%), proctitis (12.5% vs 13.3%), rectal tenesmus (3.1% vs 23.3%), asthenia (23.4% vs 61.6%) and dysuria ( 28.1% vs 30.0%). Toxicity G3/G4 diarrhea was reported in 8.3% of pts in arm B and 0% in arm A. G3/G4 lymphopenia occurred less often in arm A than in arm B (3.1% vs 23.3%). %). There was no toxicity-related death. Conclusions: The QRT SOGUG phase IIb trial met its accrual target and shows that concurrent weekly docetaxel can be administered with standard doses of radiotherapy and without increasing toxicity profile. Clinical trial information: 2008-003554-14.

Purpose: A collition tumor is characterized by the coexistence of two histologically different neoplasms that are independent of any interface mixing. Kidney collition tumors are extremely rare. Material and methods: We present the case of a patient diagnosed of a kidney collition tumor consisting of renal cell carcinoma and renal leiomyosarcoma. Results: The clinical management of this patient was complex due to the limited experience in the treatment of his kind of tumors, and to the poor results obtained with systemic treatment of the two types of tumors involved. Conclusions: There are very few communications about collition tumors of the kidney, and we consider interesting to repot the existence of these tumors as well as their clinical complexity.

Aim: Cabazitaxel (Cab) is a novel tubulin-binding taxane active in preclinical models against docetaxel-sensitive and resistant tumors. Cab is approved for the treatment of metastatic castration resistant prostate cancer (mCRPC) after docetaxel failure; however, its activity against other cancers remains unexplored. SOGUG 2011-04 is a phase II clinical trial designed to explore the efficacy of Cab in advanced genitourinary TCC after progression to a platinum-based regime. As part of this trial, a pharmacogenetic study to identify single-nucleotide polymorphisms (SNPs) predictive of Cab toxicity and response was conducted. Methods: DNA was extracted from blood samples from 45 patients in this trial. Nine key SNPs in genes involved in the pharmacokinetic and pharmacodynamic pathways of Cab (CYP3A4 rs35599367; CYP3A5 rs776746; CYP2C8 rs11572080 and rs1113129 ABCB1 rs1045642, rs1128503 and rs2032582; TUBB1 rs6070697 and rs463312) were genotyped using standard techniques. Logistic regression was used to study toxicity and response, and Cox regression to analyze progression free survival (PFS) and overall survival (OS), using an additive genetic model. Preliminary results are presented. Results: CYP3A5 rs776746 (splicing defect) protected against gastrointestinal (GI) toxicity (OR = 0.06, 95%CI = 0.007-0.63, P = 0.018) and was associated with reduced PFS (HR = 4.4, 95%CI = 1.6-11.7, P = 0.0032). Adjusting for patient prognosis, according to Bellmunt's classification, did not change the results. Furthermore ABCB1 rs1128503, rs1045642 and rs2032582 were associated with the total number of Grade 3-4 toxicity events (P values of 0.009, 0.041, and 0.043, respectively, multivariable analysis). TUBB1 Q43P missense polymorphism was associated with reduced OS (P = 0.0023) although only three patients carried this variant. Conclusions: Polymorphisms in CYP3A5 may define a subset of patients with decreased Cab activity resulting in less GI adverse events and shorter PFS. Additionally, variation in ABCB1 may be associated with the severity of Cab toxicity. These results need to be validated in larger and independent series but suggest potential markers for Cab treatment optimization. * This study has been supported by an unrestricted educational grant of Sanofi-Aventis to the Spanish GU Oncology Group (SOGUG) Disclosure: I. Duran: has participated in compensated Advisory Boards for Sanofi-Aventis; M. Climent: has participated in compensated Advisory Boards for Sanofi-Aventis. All other authors have declared no conflicts of interest.

TPS2110 Background: Recurrent GBM has a very poor prognosis and there is an unmet need for new treatment options. EGFR is an attractive therapeutic target for GBM, due to high rates of amplifcation...

2028 Background: We compared the efficacy and safety of treatment with TMZ or TMZ+BEVprior to and concomitant with radiotherapy in unresectable(GBM) patients. Methods: Between December 2009 and Apr...

Primary tumor location was pancreas in 13 pts (25.5%), lung in 11 pts (21.6%), small or large intestine in 8 pts (15.7%), appendix in 5 pts (9.8%), and other locations in 14 pts (27.5%). Results: Thirty-two pts had low grade (Ki67 20%). 49% (25) of the pts were metastatic at diagnosis. Octreoscan was positive in 15 pts with well-differentiated tumors (low and intermediate grade) and in 3 with poorly differentiated tumors (high grade). Resection of the tumor was possible in 24 pts (75%) with low-grade, three (42.9%) with intermediate and 2 (16.7%) with high grade tumors (Chi squared test, p = 0.002). All high grade NETs were treated with chemotherapy (CT) with cisplatin-etoposide. Only 8 low grade tumors and 5 intermediate grade tumors were treated with CT. Eighteen pts with low grade, 4 with intermediate and 1 with high grade tumor were treated with somatostatin analogues. Median survival was 31.36 months for pts with low grade tumors, 21 months for those with intermediate grade and 14.63 months for high grade tumors, with statistically significant differences (Chi square test, p = 0.002). Conclusion: Grade of differentiation, defined by the expression of cell proliferation marker Ki 67 protein, determines differences in the therapeutic strategy of NETs. Our results coincide with the literature regarding the significant correlation among grade of differentiation and survival in pts with NETs. It is established as the main prognostic factor that also modifies the therapeutic approach.

Background: Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer. The overall response with Bevacizumab is low in some studies. Not know the ideal method of assessing response to therapy with bevacizumab. Metabolic imaging of tumor viability with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and simultaneous anatomic localization provided by low-dose non-enhanced computed tomography (CT), can be obtained in a combined modality FDG-PET/CT scan. The purpose of this study was to evaluate the possible contribution of FDG-PET/ CT as a surrogate marker to evaluate treatment response in patients with metastatic colorectal cancer (mCRC) who had been treated with bevacizumab and standard chemotherapy. Methods: Retrospective analysis of 28 patients with advanced colorectal cancer who had been treated in the Hospital Universitario Virgen de las Nieves in Granada. Analyses included all patients who initiated bevacizumab in combination with either first-line oxaliplatin or irinotecan based regimens. FDG-PET/CT scans were performed before the start of the treatment and after six cycles of therapy. Results were compared to concurrent contrast-enhanced CT. Response to treatment was determined according to RECIST size criteria obtained from data from thin (3-5mm) slice CT, and changes in uptake of 18F-FDG uptake on PET. Results: A total of 28 patients were evaluated. Overall, 22 patients had favorable response to treatment, and only 6 had progression of disease. Complete response (CR) was evident on FDG-PET in 6/28 (21,4%) patients whereas only 5 were deemed CR by CT and partial response (PR) in 15/28 (64,3%) with both techniques. Similarly, only 1/ 28 (3,6%) lesion appeared stable by FDG-PET and CT criteria. Progression of disease (PT) was evident on FDG-PET in 6/28 (21,4%) patients whereas only 5 were deemed PT by CT. There was a strong correlation between metabolic response (changes in SUV) and objective response (r = 0.81, P

97 Background: Multidrug resistance (MDR) phenotype is the major cause of chemotherapy failure. It has been related to several proteins expression: P-glycoprotein (PgP), MRP family, LRP, and BCRP. We study the resistance pattern induced after paclitaxel and carboplatin in non-small cell lung cancer (NSCLC). Methods: We used 5 different cell lines. A549 and A427 cell lines were derived from lung epithelial carcinoma. NODO line was obtained from lung carcinoma metastases, and 3 cell lines derived from other tumours: gastric cancer (GAS), seminoma (SEM), breast cancer (MCF7). The cell lines were exposed to paclitaxel, carboplatin, and the combination of both drugs. The concentrations we used were similar to the plasma concentrations observed in patients treated previously. Results: A549 cell line did not show basal expression of MDR1, but a weak basal expression of MRP3 was observed. After chemotherapy, we observed that paclitaxel induced MDR1 and carboplatin induced MRP3. The combination of both drugs induced MDR1 and MRP3 expression, however, when paclitaxel is associated to carboplatin, MRP3 expression did not increase significantly. A427 cell line did not show basal expression of MDR1 and MRP3. Paclitaxel induced MDR1 and carboplatin induced MRP3. The association of both drugs increased significantly the expression of MDR1, and very few the expression of MRP3. NODO cell line did not show any basal expression. Paclitaxel induced MDR1 and carboplatin induced MRP3. Cell lines derived from other tumours not show any basal expression. Paclitaxel induced MDR1 in all cell lines. Carboplatin did not induce MDR1, nor MRP3 in GAS cell line. Conclusions: Plasma concentrations of paclitaxel induced MDR1 expression but not MRP3 in lung cancer and other tumours derived cell lines. Carboplatin produced overexpression of MRP3 but not MDR1 in the same cell lines. The combination of both drugs at plasma concentrations was not able to activate a new resistance mechanism in the studied cell lines, but improve the resistance mechanism induced by each one of the drugs individually.

96 Background: Non-small cell lung cancer (NSCLC) is sometimes chemoresistant and does not respond to treatment; several factors are involved in the development of chemoresistance, such as multidrug resistance (MDR) phenotype, mainly. Methods: We studied MDR1 gene expression in peripheral blood PMN of 23 patients with NSCLC, advanced stages in most of the cases, who had not received treatment previously, before (hour 0) and after (hour 6) paclitaxel-carboplatin treatment. RNA was obtained from PMN pellet by means of the protocol of trizol. RNA was checked with agarose gels, and later RT-PCR technique was carried out using specific primers. Expression levels were randomly distributed, so that overexpression under 3 was considered low level of expression, and overexpression above 4 was considered high level of expression. Results: After treatment, we found overexpression of MDR1 in 22 patients. High levels were found in 11 patients, and low levels were observed in the other 11 patients. No relation was found between this fact and the treatment response or survival rate. No significant differences in expression were found in the other variables: gender, tobacco habit, weight loss at the diagnosis, tumour staging, and tumor histology. Conclusions: We can conclude that MDR1 expression in peripheral blood is not a predictive factor for treatment response nor a prognostic factor of the disease. Despite these results, further studies are necessary on molecular biology of NSCLC in order to try to establish subgroups of patients based on genetic profiles, in which the use of microarrays could be very useful.

TPS4672 Background: Advanced transitional cell carcinoma of the urothelium (TCCU) on progression after previous cisplatin-based combination is generally an incurable disease. The appropriate management of these patients is still an unmet need. Many drugs have shown modest or no activity in previous phase 2 trials. Population heterogeneity in these studies emerges as one of the key determinants that could explain the variable outcomes. Recently, in a phase III study in this setting, prognostic factors (PF) for overall survival were identified (Bellmunt J et al, JCO 2010). Taxanes are active drugs in 2nd-line metastatic TCCU. Cabazitaxel (C) is a semi-synthetic taxane that is a poor substrate for the multidrug resistance system. C could be a valid alternative in this patient population. Methods: This is an open label phase II study of C in patients (pts) with advanced or metastatic TCCU who have progressed within 12 months after receiving a 1st-line platinum based chemotherapy. There are three treatment arms as patients will be assigned to one of three groups previously defined based on the presence of 0, 1 or 2-3 PFs as defined by Bellmunt et al. The activity of C will be assessed separately in each group and overall. The primary endpoint is response rate (RR) evaluated according to RECIST 1.1, a maximum of 35 pts are needed in each subgroup (maximum number of pts required: 105). Secondary objectives are RR in the whole population, toxicity, progression-free survival and overall survival. In addition, an external validation of the prognostic model proposed by Bellmunt will be conducted, as well as a pharmacogenomic study in order to better define the toxicity profile of the drug and the potential responders.

e13036 Background: Multidrug resistance (MDR) phenotype is the major cause of chemotherapy failure. The relationship between the expression of these markers and chemotherapy resistance is clear. We study the resistance pattern induced after treatment with paclitaxel, carboplatin in non small cell lung cancer (NSCLC). Methods: We used 5 different cell lines. A549 and A427 cell lines were derived from lung epithelial carcinoma. The NODO line was obtained from lung carcinoma , and 3 cell lines derived from other tumours . The cell lines were exposed to paclitaxel, carboplatin, and the combination of both drugs. The concentrations we used were similar to the plasma concentrations observed in patients treated previously. Results: A549 cell line did not show basal expression of MDR1, but a weak basal expression of MRP3 was observed. After chemotherapy, we observed that paclitaxel induced MDR1and carboplatin induced MRP3. The combination of both drugs induced the expression of both cell lines, however, when pacl...

Purpose: Posttranslational modifications are known to be altered in cancer cells, and loss of selected histone acetylation and methylation marks has recently been shown to predict patient outcome in human carcinoma. Materials: Since January 2002 to June 2005, 107 women with breast cancer and 108 control subjects were recruited. A sensitive SYBR green methylation-specific PCR quantitative technique was used to analyze the utility of circulating DNA with CpG island hypermethylation of APC, RAR-β, E-cadherin, ESR1 and 14-3-3σ gene promoter regions as breast cancer biomarkers. Sera were collected in 107 operable breast cancer patients (pts) previously surgery and in 60 of those pts after treatment. Respect controls, 34 had benign breast disease and 74 with no evidence of breast disease Results: Mean serum values of methylated ESR1 and 14-3-3σ gene promoters significantly differed between breast cancer patients and healthy controls (p = 0.0112 for ESR1 and p= 0.0047 for 14-3-3- σ). When their results were combined, it was found that hypermethylation of these two genes differentiated between breast cancer patients and healthy controls (p≤0.0001) with a sensitivity of 81% (95% confidence interval: 72—88%) and specificity of 88% (95% CI: 78—94%). Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p = 0.0179); and presence of methylated 14-3-3-σ was associated with T3-4 stage (OMS) (p< 0.05) and nodal positive status (p< 0.05). We observed lower methylated ERS1 or 14-3-3-σ values after surgery, respect pretreatment levels, but without an overall statistically significant difference. With a median follow up of 6 years, we found that patients with a significant decrease of sera methylated levels of both genes after surgery had better time to progression an overall survival respect patients without this observation Conclusions: These results also suggest that this panel of genes detected in ductal lavage and blood specimens could be useful to biomarkers for early detection breast cancer. These findings cast some doubts on the utility for early cancer diagnosis of highly sensitive techniques to identify hypermethylation of specific gene promoters in DNA extracted from serum. Although numerous issues remain to be resolved, the quantitative measurement of circulating methylated DNA is a promising tool for cancer risk assessment.