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Martin M.,Complutense University of Madrid | Prat A.,Vall dHebron Institute of Oncology VHIO | Prat A.,Autonomous University of Barcelona | Rodriguez-Lescure A.,Hospital General de Elche | And 25 more authors.
Breast Cancer Research and Treatment | Year: 2013

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical-pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel. © 2013 The Author(s). Source


Codony-Servat J.,University of Barcelona | Garcia-Albeniz X.,University of Barcelona | Pericay C.,Hospital Parc Tauli | Alonso V.,Hospital Miguel Servet | And 6 more authors.
Medical Oncology | Year: 2013

The FAS/FASL system, comprising membrane-bound (mFAS and mFASL) and soluble forms (sFAS and sFASL), has been related to apoptosis driven by chemotherapy administration. In vitro experiments show chemotherapy upregulating membrane-bound forms, leading to an increase of receptor availability (at 24-72 h) and favoring apoptosis. The regulatory effect of chemotherapy on sFAS in patients has never been explored prospectively in advanced colorectal cancer (ACRC). We performed a pharmacodynamic study to address sFAS/sFASL variation. A prospective phase II translational multicenter study was designed to evaluate progression-free rate (PFR) in patients with ACRC treated with irinotecan and cetuximab in third-line therapy. The effect of sFAS was studied in vitro in colorectal cancer cell lines. Our results showed that statistically significant changes were observed in sFAS at 24-72 h compared to baseline levels in the pharmacodynamic study. Of the 93 patients enrolled in the prospective study in third-line therapy with cetuximab-irinotecan, 85 were evaluated for sFAS/sFASL changes at 48 h. There was no difference in PFR at 4 months between patients with sFAS and sFASL changes. In vitro analysis showed that although LoVo cell lines were sensitive to oxaliplatin and fluorouracil due to modulation of sFAS and FAS, HT29 lines were not. In summary, chemotherapy regulates FAS soluble fractions in vitro and in vivo, but does not predict PFR in ACRC patients undergoing third-line therapy with the combination of cetuximab and irinotecan. © 2013 Springer Science+Business Media New York. Source


Portillo J.A.,Hospital Universitario Marques Of Valdecilla Humv | Madero R.,Hospital Universitario La Paz | Solsona E.,Instituto Valenciano Of Oncologia Ivo | Fernandez J.M.,University of Oviedo | And 5 more authors.
Actas Urologicas Espanolas | Year: 2014

Objectives To analyze if the true number of BCG instillations applied in non-muscle invasive bladder tumors has any influence on their prognosis as well as other tumor and clinical characteristics: age, sex, different protocols, BCG dose, whether primary or recurrent, solitary or multiple, tumor size G3 or Cis. Patients and methods A total of 324 high grade NMIBC (15 TaG3, 184 T1G3, 125 Cis) out of 1491 cases included in the CUETO database were analyzed. Following 6 post transurethral resection (RTU) BCG instillations, the patients were scheduled to receive one instillation every two weeks (3-6 times), for a total of 9-12 instillations. One third of the dose (27 mg) (112 cases) or total dose of 81 mg (212 cases). Mean follow-up was 59.6 months. Statistical Analysis: Kaplan-Meier, Cox-regression (uni-multivariate). Results A higher level of recurrence (p = 0.032) and progression (P =.013) risk as well as worse Ca-specific survival (P =.005) were obtained if there were fewer than 12 instillations with the Kaplan-Meier and Cox-regression multivariate analysis. A 27 mg (P =.008) dosage and being a female (P <.001) were independent factors for a higher recurrence risk, but not for progression or Ca-specific survival. The remaining characteristics studied were not statistically significant. Conclusions In accordance with the results obtained, we can conclude that the number of BCG instillations applied has some influence on the outcome of high grade NMIBC. The optimum number of instillations as well as their time of application must still be determined. A dose of 27 mg and being a female are predictive factors of recurrence. © 2013 AEU. Publicado por Elsevier España, S.L. Todos los derechos reservados. Source


Climent M.A.,Instituto Valenciano Of Oncologia Ivo | Piulats J.M.,Institute Catala dOncologia ICO | Sanchez-Hernandez A.,Hospital Provincial de Castellon | Arranz J.A.,Hospital General Universitario Gregorio Maranon | And 7 more authors.
Critical Reviews in Oncology/Hematology | Year: 2012

Prostate cancer is the most prevalent urogenital malignancy. However, despite initial disease control using androgen deprivation, most of patients eventually develop progressive disease that is resistant to further hormone manipulation. For these patients with castration-resistant prostate cancer (CRPC), and particularly patients with metastatic disease, options have been limited, and prognosis is grim. However, as newer regimens and agents become available, higher rates of objective and biochemical response are being achieved, providing renewed hope for the management of these patients. With the aim of facilitating the treatment of these patients, the Spanish Oncology Genitourinary Group (SOGUG) has issued a series of the recommendations which have been collected in this review. Each recommendation is accompanied by the appropriate level of evidence and grade of recommendation on the basis of the characteristics of the data available. © 2012 Elsevier Ireland Ltd. Source


Solsona E.,Instituto Valenciano Of Oncologia Ivo
Archivos Espanoles de Urologia | Year: 2012

Radical prostatectomy is an excellent salvage method for patients with prostatic cancer when radical radiotherapy or brachytherapy fail. To define local failure is not always reliable; nevertheless, performing a prostatic biopsy two years after treatment could reach an early diagnosis. Another accepted attitude is to perform the biopsy after biochemical recurrence, but sometimes the pathological stage is already locally advanced tumor. It is also difficult to determine which patients are suitable for this rescue treatment, probably those with locally confined tumors and with favorable PSA kinetics, PSA velocity below 2.0 or a PSA doubling time over 12 months, and in whom detectable PSA is reached 2 years after treatment. These patients are suitable for radical prostatectomy if they have a live expectancy of more than 10 years. Although rescue radical prostatectomy has a higher rate of complications and worse functional results, cancer-specific survival rates are high, and remain high after 15 years of follow-up. Currently, new surgical improvements and new radiotherapy technology are diminishing surgical complications and improving functional results. In summary radical prostatectomy is a feasible rescue procedure after radiotherapy failure although the complications rate remains higher than prostatectomy as initial therapy. Source

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