المؤلفون: de Velasco, Guillermo, Alonso-Gordoa, Teresa, Rodríguez-Vida, Alejo, Anguera, Georgia, Campayo, Marc, Pinto, Álvaro, Martínez Ortega, Esther, Gallardo, Enrique, Fernández Núñez, Natalia, García-Carbonero, Iciar, Reig, Oscar, Méndez-Vidal, María José, Fernández-Calvo, Ovidio, Cassinello, Natalia Vidal, Torregrosa, Dolores, López-Martín, Ana, Rosero, Adriana, Valiente, Patricia G., Garcías de España, Carmen, Climent, Miguel A.

المصدر: Clinical Genitourinary Cancer; Jun2023, Vol. 21 Issue 3, pe166-e174, 9p

مصطلحات موضوعية: RENAL cell carcinoma, SUNITINIB, TREATMENT effectiveness, CANCER immunotherapy, NEPHRECTOMY

مستخلص: Sunitinib, a tyrosine kinase inhibitor, has been central for the treatment of metastatic renal cell carcinoma until the recent development of immunotherapy. This study analyzed the characteristics of patients with complete response to sunitinib (n = 62) to understand associations with clinical variables. A complete response to sunitinib could be achieved irrespective of prognostic group, metastasis site or histology type. Introduction: The long-term clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) and a complete response (CR) to the tyrosine kinase inhibitor (TKI) sunitinib are poorly known. The characteristics of these patients could reveal previously undetected associations with clinical variables. Patients and Methods: This observational, retrospective study (ATILA) used data from a registry of patients with mRCC who had received first-line sunitinib and had achieved CR from 2007 to 2018 in Spain. Results: Sixty-two patients with CR were included; 48 patients (77.4%) received sunitinib in monotherapy and 14 (22.6%) combined with or followed by local treatment. Median age was 58.5 years (range, 32-81). Most patients (79.0%) had clear cell histology and had undergone previous nephrectomy (90.3%). The majority (70.2%) had an intermediate IMDC prognosis, 23% favorable and 7.0% poor. The median time on treatment with sunitinib was 28.2 months (IQR, 16.7-41.0) and the median time to CR was 10.9 months (IQR, 7.2-19.3). After a median follow-up of 8 years (range, 3-13 years), the median PFS was not reached. The overall median duration of complete response was 64.1 months (IQR, 32.2-99.4). The tolerance and safety profile of sunitinib was consistent with previous reports. Conclusion: Durable CR to sunitinib was observed in patients regardless the prognosis group, metastasis site or histology type, with 75% of patients remaining in CR after 10 years. Clinicaltrials.gov: NCT03916458. [ABSTRACT FROM AUTHOR]

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المؤلفون: Climent, Miguel A.¹ (AUTHOR) macliment@fivo.org, Font, Albert² (AUTHOR) afont@iconcologia.net, Durán, Ignacio³ (AUTHOR) ignacioduranmartinez@gmail.com, Puente, Javier⁴ (AUTHOR) jpuente.hcsc@salud.madrid.org, José Méndez-Vidal, María⁵ (AUTHOR) mjosemv@yahoo.es, Sáez, María Isabel⁶ (AUTHOR) msaez.med@gmail.com, Santander Lobera, Carmen⁷ (AUTHOR) csantlob@yahoo.es, Ángel Arranz Arija, Jóse⁸ (AUTHOR) jarranza.oncomed@gmail.com, González-del-Alba, Aranzazu⁹ (AUTHOR) aranglezalba@yahoo.es, Sánchez-Hernandez, Alfredo¹⁰ (AUTHOR) asanchezh@seom.org, Juan Fita, Maria Jose¹ (AUTHOR) mjjuan@fivo.org, Esteban, Emilio¹¹ (AUTHOR) eestebang@seom.org, Alonso-Gordoa, Teresa¹² (AUTHOR) talonso@oncologiahrc.com, Mellado Gonzalez, Begoña¹³ (AUTHOR) bmellado@clinic.cat, Maroto, Pablo¹⁴ (AUTHOR) jmaroto@santpau.cat, Lázaro-Quintela, Martín¹⁵ (AUTHOR) martin.lazaro.quintela@sergas.es, Cassinello-Espinosa, Javier¹⁶ (AUTHOR) jacaes@sescam.jccm.es, Pérez-Valderrama, Begoña¹⁷ (AUTHOR) bperezv@gmail.com, Garcias, Carmen¹⁸ (AUTHOR) mariad.garcias@ssib.es, Castellano, Daniel¹⁹ (AUTHOR) cdanicas@hotmail.com

المصدر: European Journal of Cancer. Nov2022, Vol. 175, p110-119. 10p.

مصطلحات موضوعية: *DISEASE progression, *CONFIDENCE intervals, *ORAL drug administration, *METASTASIS, *ABIRATERONE acetate, *ANTINEOPLASTIC agents, *TREATMENT effectiveness, *RANDOMIZED controlled trials, *COMPARATIVE studies, *DOCETAXEL, *DESCRIPTIVE statistics, *PREDNISONE, *PROGRESSION-free survival, *PATIENT safety, *PHARMACODYNAMICS

مستخلص: We aimed to compare the efficacy and safety of maintaining or withdrawing abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer who had experienced cancer progression to this treatment and were beginning a docetaxel-based therapy. Phase II, randomised, open-label study conducted in patients with metastatic castration-resistant prostate cancer who were asymptomatic or mildly symptomatic. After open-label treatment with AAP, patients who had experienced cancer progression to AAP were randomised to 75 mg/m2 of docetaxel plus AAP or to receive 75 mg/m2 of docetaxel plus 10 mg of prednisone orally daily. The primary outcome was the radiographic progression-free survival rate at 12 months as evaluated by the investigators in all randomised patients. A total of 148 patients were included in open-label treatment with AAP, and of them, 94 patients were randomised to receive either docetaxel plus AAP (intervention group; n = 47) or docetaxel plus prednisone (control group; n = 47). The 12-month radiographic progression-free survival rates did not differ between the intervention group (34.9%; 95% CI 20.7–49.2) and the control group (33.9%; 95% CI 19.5–48.3). There were no significant differences in the time to radiographic progression and the overall survival between the intervention and control groups. Grade 3–5 neutropenia with the combination of docetaxel plus prednisone and AA was more frequent than with docetaxel plus prednisone (59.6% versus 27.7%). Our results indicate that the therapeutic strategy of maintaining AAP added to docetaxel in chemotherapy-naïve patients who have experienced cancer progression to AAP treatment should not be further evaluated and should be avoided in clinical practice. NCT02036060 https://clinicaltrials.gov/ct2/show/NCT02036060Test. • Docetaxel plus abiraterone acetate plus prednisone (AAP) versus docetaxel plus prednisone after progression to AAP in metastatic castration-resistant prostate cancer. • The 12-month radiographic progression-free survival rates did not differ (34.9% versus 33.9%). • No differences in the time to radiographic progression and overall survival. • Higher frequency of grade 3–5 and serious adverse events with the intervention. • Maintaining AAP added to docetaxel after progression to AAP is not an option. [ABSTRACT FROM AUTHOR]

المؤلفون: García-del-Muro, Xavier, Durán, Ignacio, Perez-Gracia, Jose Luis, Climent, Miguel Ángel, Mellado, Begoña, Virizuela, Juan A., Castellano, Daniel E., González del Alba, Aranzazu, García Carbonero, Iciar, Álvarez-Fernández, Carlos, García-Donas, Jesús, Gil-Martin, Marta, Hernández, Alvaro-González

المصدر: Clinical Genitourinary Cancer; Aug2022, Vol. 20 Issue 4, p388.e1-388.e10, 10p

مصطلحات موضوعية: BIOMARKERS, RENAL cell carcinoma, INTERFERON alpha, TREATMENT effectiveness, CANCER immunotherapy

مستخلص: Phase I/II translational trial evaluating the molecular determinants of pazopanib plus interferon alpha efficacy in advanced renal cell carcinoma. The expression levels of TNF- a, endoglin and PDL1 correlated with response at eight weeks after treatment initiation. This suggests a crucial role of vascular remodelling and inflammatory-mediated immune cell infiltration for an optimal response to pazopanib plus interferon alpha combination. Introduction: The therapeutic repertoire available for advanced renal cell carcinoma (RCC), including tyrosine kinase inhibitors (TKIs) and immunotherapy, required for molecular biomarkers for response. Patients and Methods: This was a phase I to II trial on the combination of pazopanib with interferonalpha (INF-2A) as first-line treatment for advanced RCC. The primary endpoint was recommended phase II dose (RP2D) and efficacy in terms of objective response rate (ORR, RECIST 1.1 criteria). Secondary endpoints included safety and a translational study of molecular biomarkers in serum and exosomes from peripheral blood samples at three-time points: baseline, 8 weeks of treatment, and progression of the disease. Results: Between July 2011 and July 2017, 53 eligible patients were treated and followed up (I, n = 20; II, n = 33). Pazopanib 800 mg + INF-2A 3 MIUs showed a manageable safety profile; therefore, it was selected for dose expansion. Overall, grade 3/4 toxicities were reported in 24 (72.7%) patients. The ORR was 27.2%. The 12-month OS rate was 83.6% (median not reached), and after 30.9 months of followup, 24 (72.7%) patients were still alive. CCL2, IL8, TNF- a, and PD-L1 were significantly overexpressed after treatment initiation, while TGF- ß1 and CCL5 were significantly decreased. TNF- a, endoglin, and PDL1 expression are correlated with the response after treatment initiation. Conclusion: The trial did not reach its pre-specified target ORR. However, OS was longer than expected with pazopanib monotherapy. Changes in the molecular profile suggest a crucial role of vascular remodeling and inflammatory-mediated immune cell infiltration in optimal response to pazopanib plus INF-2A. [ABSTRACT FROM AUTHOR]

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المؤلفون: Climent, Miguel A.¹ macliment@fivo.org, Muñoz-Langa, José² munyoz_joslan@gva.es, Basterretxea-Badiola, Laura³ Laura.basterrecheabadiola@osakidetza.eus, Santander-Lobera, Carmen⁴ csantlob@yahoo.es

المصدر: Critical Reviews in Oncology/Hematology. Jan2018, Vol. 121, p45-50. 6p.

مصطلحات موضوعية: *META-analysis, *RENAL cell carcinoma, *CANCER treatment, *COMORBIDITY, *CLINICAL trials, *PATIENTS

مستخلص: A systematic review was conducted to identify real world studies reporting outcomes after first-line pazopanib in patients with metastatic renal cell carcinoma. Studies had to be observational and report survival data in terms of progression-free survival and overall survival in order to conduct meta-analysis techniques. These real-world data were compared to those obtained in the phase II and III randomized controlled trials of pazopanib. Real world evidence showed that the clinical and safety outcomes were consistent with those observed in the clinical trials despite the inclusion of unselected patients with a wide spectrum of prognostic features and comorbidities. Similarly to the results of the pivotal studies, good prognosis patients had the most benefit from pazopanib. Further investigation is needed to complement evidence from clinical trials, in particular focused on patient-centered outcomes. [ABSTRACT FROM AUTHOR]

المؤلفون: Climent, Miguel Ángel¹ macliment@fivo.org, Pérez-Valderrama, Begoña², Mellado, Begoña³, Fernández Parra, Eva María⁴, Fernández Calvo, Ovidio⁵, Ochoa de Olza, María⁶, Muinelo Romay, Laura⁷, Anido, Urbano⁸, Domenech, Montserrat⁹, Hernando Polo, Susana¹⁰, Arranz Arija, José Ángel¹¹, Caballero, Cristina¹², Juan Fita, María José¹, Castellano, Daniel¹³

المصدر: European Journal of Cancer. Dec2017, Vol. 87, p30-37. 8p.

مصطلحات موضوعية: *DOCETAXEL, *CLINICAL trials, *DRUG toxicity, *LEUCOPENIA, *NEUTROPENIA, *PREDNISONE, *PROSTATE tumors, *SURVIVAL, *THROMBOCYTOPENIA, *PROSTATE-specific antigen, *TREATMENT effectiveness, *CABAZITAXEL

مستخلص: Aim Cabazitaxel (CBZ), a novel tubulin-binding taxane, improves overall survival in metastatic castration-resistant prostate cancer (mCRPC) that progresses during or after docetaxel treatment. We have designed a phase II study to evaluate the efficacy and safety of CBZ as a weekly schedule for ‘unfit’ mCRPC patients after docetaxel failure. Methods In this single arm phase II study. CBZ was weekly administered in 1-hour infusion on days 1, 8, 15 and 22, every 5 weeks at 10 mg/m 2 to eligible ‘unfit’ patients; oral prednisone (5 mg) was administered twice a day. Circulating tumour cells (CTCs) were also collected. New treatment scheme was considered effective if at least 65% of patients met a clinical benefit criteria based on prostate-specific antigen (PSA)-progression-free survival (PFS) values at week 12. Results Seventy patients (median age: 73.9 years) were enrolled; overall, 71.4% had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 2; and 84%, 16% and 11% had bone, liver and lung metastases, respectively. Objective partial response or stable disease was achieved in 61% of patients, while PSA responses of ≥50% and ≥80% were observed in 34.8% and 10.6%, respectively. The median PSA-PFS was 4.8 months; and 68.6% of patients had no progression at week 12. The most frequent grade 3/4 toxicities were neutropenia (2.8%), leukopenia (5.7%) and thrombocytopaenia (9%); no cases of febrile neutropenia were reported. Early CTC response was significantly correlated with PSA-PFS. Conclusions CBZ/prednisone administered weekly to ‘unfit’ mCRPC patients appears to be as effective as classical standard 3-week scheme (TROPIC study) but with significantly lower toxicities and better tolerance. Early CTC response appears to be valuable as an early end-point of therapeutic efficacy. [ABSTRACT FROM AUTHOR]

المؤلفون: Climent, Miguel Ángel, Torregrosa, M a Dolores, Vázquez, Sergio, Gironés, Regina, Arranz, José Angel, Torregrosa, Ma Dolores

المصدر: Cancer Treatment Reviews; Apr2017, Vol. 55, p173-180, 8p

مستخلص: Prostate cancer largely affects aged men and as life expectancy continues to increase, it is likely to be a growing burden requiring an adequate management. Aging is a heterogeneous process, thus, to assess the individual state of health when making decisions is essential. Comprehensive geriatric assessment allows a detailed evaluation of the state of health of a specific subject and can modify the therapeutic decision. It is still not commonly used because it is time consuming. Chemotherapy should be administered equally in aged well-fit patients as in the general population as per the SIOG (International society of geriatric oncology) recommendations for geriatric evaluation and treatment in prostate cancer patients. Chemotherapy with docetaxel or cabazitaxel is expected to have an efficacy and toxicity similar to younger patients and they might be considered treatment options for these patients among others. In vulnerable or frail patients, weekly or biweekly docetaxel regimens are acceptable treatment options. [ABSTRACT FROM AUTHOR]

: Copyright of Cancer Treatment Reviews is the property of W B Saunders and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Nescolarde-Selva, Josué-Antonio, Usó-Doménech, José-Luis, Lloret-Climent, Miguel

المصدر: Ecological Complexity; Dec2016, Vol. 28, p62-68, 7p

مصطلحات موضوعية: ECOLOGICAL models, SENSITIVITY analysis, UNCERTAINTY, DYNAMICAL systems, NUMERICAL analysis, DATA analysis

مستخلص: In previous work by the authors about dynamic system modeling, basic ecosystems concepts and their application to ecological modeling theory were formalized. Measuring how a variable effects certain processes leads to improvements in dynamic systems modelling and facilitates the author’s study of system diversity in which model sensitivity is a key theme. Initially, some variables and their numeric data are used for modeling. Predictions from the constructed models depend on these data. Generic study of sensitivity aims to show to what degree model behavior is altered by modification of some specific data. If small variations cause important modifications in the model’s global behavior then the model is very sensitive in relation to the variables used. If uncertain systems are considered, then it is important to submit the system to extreme situations and analyze its behavior. In this article, some indexes of uncertainty will be defined in order to determine the variables' influence in the case of extreme changes. This will permit analysis of the system’s sensitivity in relation to several simulations. [ABSTRACT FROM AUTHOR]

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المؤلفون: Nescolarde-Selva, Josué-Antonio, Usó-Doménech, Josep-Lluis, Lloret-Climent, Miguel, Fan, Meng

المصدر: Ecological Complexity; Jun2016, Vol. 26, p79-88, 10p

مصطلحات موضوعية: STOCHASTIC processes, ECOLOGICAL models, REGRESSION analysis, GAUSSIAN distribution, CISTACEAE

مستخلص: A flow equation obtained through multiple linear regressions is a static concept fixed for a time t . However, experience says that the temporal component makes the information obtained from the flow equation in terms of coefficients of determination. In this paper we show that a 1-degree variation in such coefficients behaves like a Wiener process based on the Gaussian distribution. As an application, we study the destruction of fruits in Cistus albidus L. [ABSTRACT FROM AUTHOR]

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المؤلفون: Climent, Miguel Ángel¹ macliment@fivo.org, León-Mateos, Luis², González del Alba, Aránzazu³, Pérez-Valderrama, Begoña⁴, Méndez-Vidal, Mª José⁵, Mellado, Begoña⁶, Arranz, José Ángel⁷, Sánchez-Hernández, Alfredo⁸, Cassinello, Javier⁹, Olmos, David¹⁰, Carles, Joan¹¹

المصدر: Critical Reviews in Oncology/Hematology. Nov2015, Vol. 96 Issue 2, p308-318. 11p.

مصطلحات موضوعية: *PROSTATE cancer treatment, *CANCER hormone therapy, *CANCER chemotherapy, *RANDOMIZED controlled trials, *MEDICAL decision making, *PROSTATE cancer patients

مستخلص: Summary Prostate cancer is the most prevalent male urogenital malignancy. Approximately 30% of patients with prostate cancer will develop advanced disease. Androgen deprivation therapy achieves disease control in about 90% of these patients, but the majority of them will eventually develop progressive disease, a status called castration-resistant prostate carcinoma (CRPC). However, in recent years, several new therapy strategies, such as immunotherapy, hormonal manipulations, chemotherapy agents and some bone-targeted therapies, have demonstrated an improvement in terms of overall survival in controlled trials. In 2012, the Spanish Oncology Genitourinary Group (SOGUG) published its recommendations for the treatment of patients with CRPC. Due to the recent appearance of important new data and the complexity of decision-making in this field, SOGUG herein provides updated recommendations for the treatment of patients with metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

المؤلفون: Nescolarde-Selva, Josué-Antonio, Usó-Doménech, Josep-Lluis, Lloret-Climent, Miguel, González-Franco, Lucía

المصدر: Ecological Complexity; Mar2015, Vol. 21, p27-33, 7p

مصطلحات موضوعية: MATHEMATICAL formulas, MATHEMATICAL models, STATISTICAL linguistics, NATURAL language processing, PARAMETER estimation, POISSON distribution

مستخلص: Ecological models written in a mathematical language L(M) or model language, with a given style or methodology can be considered as a text. It is possible to apply statistical linguistic laws and the experimental results demonstrate that the behaviour of a mathematical model is the same of any literary text of any natural language. A text has the following characteristics: (a) the variables, its transformed functions and parameters are the lexic units or LUN of ecological models; (b) the syllables are constituted by a LUN, or a chain of them, separated by operating or ordering LUNs; (c) the flow equations are words; and (d) the distribution of words (LUM and CLUN) according to their lengths is based on a Poisson distribution, the Chebanov's law. It is founded on Vakar's formula, that is calculated likewise the linguistic entropy for L(M). We will apply these ideas over practical examples using MARIOLA model. In this paper it will be studied the problem of the lengths of the simple lexic units composed lexic units and words of text models, expressing these lengths in number of the primitive symbols, and syllables. The use of these linguistic laws renders it possible to indicate the degree of information given by an ecological model. [ABSTRACT FROM AUTHOR]

: Copyright of Ecological Complexity is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)