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Institution

Hebron University

EducationHebron, Palestinian Territory
About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.


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Journal ArticleDOI
TL;DR: In this paper, a multivariable logistic regression model was used to identify predictors of ICPi-AKI and its recovery, and the effect of rechallenge versus no re-challenge on survival was estimated.
Abstract: Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results ICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

74 citations

Journal ArticleDOI
15 Apr 2003-Cancer
TL;DR: The supplementation with daily oral folate could reduce the incidence of hematologic toxicities while preserving the antitumor activity of pemetrexed.
Abstract: Pemetrexed disodium (ALIMTa, [pemetrexed], LY231514; Eli Lilly and Company; Indianapolis, IN), a novel antifolate antimetabolite with multiple enzyme targets involved in both pyrimidine and purine synthesis, has entered clinical trials due to its favorable pleclinical profile. Many studies utilizing the drug, as a single or combination agent, are currently ongoing, including Phase III trials in mesothelioma, nonsmall cell lung carcinoma (NSCLC) and pancreatic cancer. Promising feasibility and activity data have been obtained with pemetrexed in combination with platinum compounds and gemcitabine. The supplementation with daily oral folate could reduce the incidence of hematologic toxicities while preserving the antitumor activity of pemetrexed.

73 citations

Journal ArticleDOI
TL;DR: It was used to show that robust Akt inhibition in tumors from patients treated with GDC-0068 is achievable, supporting the clinical development of this compound in defined patient populations.
Abstract: Purpose: The oncogenic PI3K/Akt/mTOR pathway is an attractive therapeutic target in cancer. However, it is unknown whether the pathway blockade required for tumor growth inhibition is clinically achievable. Therefore, we conducted pharmacodynamic studies with GDC-0068, an ATP competitive, selective Akt1/2/3 inhibitor, in preclinical models and in patients treated with this compound. Experimental Design: We used a reverse phase protein array (RPPA) platform to identify a biomarker set indicative of Akt inhibition in cell lines and human-tumor xenografts, and correlated the degree of pathway inhibition with antitumor activity. Akt pathway activity was measured using this biomarker set in pre- and post-dose tumor biopsies from patients treated with GDC-0068 in the dose escalation clinical trial. Results: The set of biomarkers of Akt inhibition is composed of 10 phosphoproteins, including Akt and PRAS40, and is modulated in a dose-dependent fashion, both in vitro and in vivo . In human-tumor xenografts, this dose dependency significantly correlated with tumor growth inhibition. Tumor biopsies from patients treated with GDC-0068 at clinically achievable doses attained a degree of biomarker inhibition that correlated with tumor growth inhibition in preclinical models. In these clinical samples, compensatory feedback activation of ERK and HER3 was observed, consistent with preclinical observations. Conclusion: This study identified a set of biomarkers of Akt inhibition that can be used in the clinical setting to assess target engagement. Here, it was used to show that robust Akt inhibition in tumors from patients treated with GDC-0068 is achievable, supporting the clinical development of this compound in defined patient populations. Clin Cancer Res; 19(24); 6976–86. ©2013 AACR .

73 citations

Journal ArticleDOI
TL;DR: The authors are now at the stage where breast cancer treatment will be determined by tumor biology as well as patient characteristics, and improved molecular characterization and greater understanding of tumorigenesis will enable more individualized treatment.

73 citations

Journal ArticleDOI
José Baselga1
TL;DR: The conclusion that concomitant gefitinib administration does not add clinical benefit to conventional chemotherapy in NSCLC seems, therefore, irrefutable.
Abstract: In this issue of the Journal of Clinical Oncology are the final results of two large phase III randomized controlled trials of the anti– epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in combination with chemotherapy in untreated patients with advanced non–smallcell lung cancer (NSCLC) [1,2]. In these two trials, with more than 2,000 patients combined, the addition of gefitinib to chemotherapy failed to meet either the primary end point of survival or the secondary end points of time to disease progression or response rates. There was not even a suggestion of a nonsignificant trend in any of these end points in favor of gefitinib. In addition, a similar absence of benefit of two comparable phase III studies in NSCLC with erlonitib, another EGFR tyrosine kinase inhibitor, has been recently reported. The two gefitinib trials, INTACT 1 and 2, were well designed, adequately powered, and well conducted. The conclusion that concomitant gefitinib administration does not add clinical benefit to conventional chemotherapy in NSCLC seems, therefore, irrefutable. These results would not have been readily anticipated a priori for a series of reasons: first, gefitinib has demonstrated well-documented activity as a single agent in the initial phase I studies that included a large number of patients with NSCLC, and the antitumor activity of gefitinib has been confirmed in two large phase II studies in the secondand third-line setting, with response rates ranging from 9% to 18%, depending on the study and the dose [3,4]. Second, unlike with triplet chemotherapy combinations, full doses of chemotherapy could be given in combination with gefitinib, because no overlapping toxicities between gefitinib and chemotherapy have been observed in the phase I studies with these combinations. Third, available preclinical data for gefitinib combined with chemotherapy were impressively additive [5,6]. Given the outcome of the INTACT trials, it is obvious that some of these observations were incorrect or that some additional key determinants had not been taken into account. The first criticism of these trials is the lack of selection of the subset of patients likely to respond to gefitinib. Unlike trastuzumab, there are not available predictive markers of sensitivity to anti-EGFR agents; in fact, there is evidence of a lack of correlation between EGFR expression levels in the tumor and response to anti-EGFR agents, and a retrospective analysis of tumor samples from the gefitinib phase II single agent studies in NSCLC has confirmed this lack of correlation with gefitinib as well [7,8]. It is, therefore, possible that in a situation in which the responding phenotype to gefitinib has not been yet characterized, the molecular heterogeneity of lung cancer could have resulted in a false-negative result in the overall study population [9]. Although there was no evidence of patient enrichment in the phase II studies in favor of treatment sensitive subtypes or a suggestion of a negative effect in nonresponders, it would have been extremely important to have collected tumor samples to allow for post hoc clinical correlations, assuming a molecular signature of receptor sensitivity is identified. However, let us go back to the trastuzumab comparison. The initial pivotal studies with trastuzumab showed single-agent activity and improvement in survival when combined with chemotherapy in a suboptimal population because, in addition to patients with 3 HER2 overexpressing tumors, patients with 2 HER2 ovexpressing tumors were also included [10,11]; it is now known that 2 HER2 overexpressing, fluorescence in situ hybridization–negative tumors do not respond to trastuzumab [12]. The consequence was that the combined response rate in 2 and 3 HER2 overexpressing breast tumors to single agent trastuJOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 22 NUMBER 5 MARCH 1 2004

73 citations


Authors

Showing all 2723 results

NameH-indexPapersCitations
José Baselga156707122498
M. I. Martínez134125179885
Josep Tabernero11180368982
Jordi Rello10369435994
Xavier Montalban9576252842
James M. Downey9138129506
Enriqueta Felip8362253364
Joaquim Bellmunt8266041472
Joan Montaner8048922413
Marc Miravitlles7665125671
David H. Salat7524136779
Eduard Gratacós7553120178
Alex Rovira7435619586
Ramon Bataller7228319316
Maria Buti7149326596
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20232
202212
2021568
2020545
2019483
2018385