Abstract:
:Introduction and objectives: Metastatic penile squamous cell carcinoma (PSCC) is associated with dismal outcomes with median overall survival (OS) of 6-12 months in the first-line and <6 months in the salvage setting. Given the rarity of this disease, randomized trials are difficult. Prognostic risk models may assist in rational drug development by comparing observed outcomes in nonrandomized phase II studies and retrospective data vs. predicted outcomes based on baseline prognostic factors in the context of historically used agents. In this retrospective study, we constructed a prognostic model in the salvage setting of PSCC patients receiving second or later line systemic treatment, and also explored differences in outcomes based on type of treatment. Materials and methods: We performed a chart review to identify patients with locally advanced unresectable or metastatic PSCC who received second or later line systemic treatment in centers from North America and Europe. The primary outcome was OS from initiation of treatment, with secondary outcomes being progression-free survival (PFS) and response rate (RR). OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify prognostic factors for outcomes using univariable and multivariable models. Results: Sixty-five patients were eligible. Seventeen of 63 evaluable patients had a response (27.0%, 95% confidence interval [CI] = 16.6-39.7%) and median OS and PFS were 20 (95% CI = 20-21) and 12 (95% CI = 12, 16) weeks, respectively. Visceral metastasis (VM) and hemoglobin (Hb) ≤ 10 gm/dl were consistently significant poor prognostic factors for both OS and PFS, and Hb was also prognostic for response. The 28 patients with neither risk factor had a median OS (95% CI) of 24 (20-40) weeks and 1-year (95% CI) OS of 13.7% (4.4-42.7%), while the 37 patients with 1 or 2 risk factors had median OS (95% CI) of 20 (16-20) weeks and 1-year (95% CI) OS of 6.7% (1.8-24.9%). Cetuximab-including regimens were associated with a trend for improved RR compared to other agents (Odds ratio = 5.05, 95% CI = 0.84-30.37, p = 0.077). Taxanes vs. non-taxane, and combination vs. single agent therapy was not associated with improved outcomes. The study is limited by its modest sample size. Conclusion: This is the first prognostic classification proposed for patients receiving salvage systemic therapy for advanced PSCC. The presence of VM and Hb ≤ 10 gm/dl was associated with poor OS and PFS. Cetuximab appeared to be associated with better RR. This prognostic model may assist in salvage therapy drug development for this orphan disease by improving interpretation of outcomes seen in nonrandomized data.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Buonerba C,Di Lorenzo G,Pond G,Cartenì G,Scagliarini S,Rozzi A,Quevedo FJ,Dorff T,Nappi L,Lanzetta G,Pagliaro L,Eigl BJ,Naik G,Ferro M,Galdiero M,De Placido S,Sonpavde Gdoi
10.3389/fphar.2016.00487subject
Has Abstractpub_date
2016-12-20 00:00:00pages
487issn
1663-9812journal_volume
7pub_type
杂志文章abstract::Aims and Hypothesis: This study aims to investigate the mechanism involved in intracellular regulation of EGFR degradation induced by EGF. Methods: Phosphorylation of proteins related to EGFR signaling was examined by western blot analysis. Activation, connection between Rab35 and folliculin (FLCN) were assessed by pu...
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doi:10.3389/fphar.2017.00688
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abstract::Clopidogrel is an essential antiplatelet drug used to prevent thrombosis complications associated with atherosclerosis. However, hepatotoxicity is a potential adverse effect related to clopidogrel therapy. Exosome-derived miRNAs may be useful for improved monitoring of drug response and hepatotoxicity risk. In the pre...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00906
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abstract::Cannabis extracts in oil are becoming increasingly available, and, during the last years, there has been growing public and scientific interest about therapeutic properties of these compounds for the treatment of several neurologic diseases, not just epilepsy. The discovered role of the endocannabinoid system in epile...
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pub_type: 杂志文章,评审
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abstract:Background:Brazilian patients have legal right to access unlicensed medicines undergoing clinical research, if there is evidence of efficacy and safety. This study investigated the occurrence of serious adverse events related to very high-cost medicines from clinical studies, expanded access and compassionate use progr...
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doi:10.3389/fphar.2020.00752
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abstract::The skin is the first line of defense against pathogen and other environmental pollutant. The body is constantly exposed to reactive oxygen species (ROS) that stimulates inflammatory process in the skin. Many studies have linked ROS to various inflammatory skin diseases. Patients with skin diseases face various challe...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.01086
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abstract::The recent publication of the σ1R crystal structure is an important cornerstone for the derivation of more accurate activity prediction models. We report here a comparative study involving a set of more than 25,000 structures from our internal database that had been screened for σ1R affinity. Using the recently publis...
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doi:10.3389/fphar.2019.00519
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abstract::Cardiovascular diseases (CVDs) are the major public health problem and a leading cause of morbidity and mortality on a global basis. Wenxin Keli (WXKL), a formally classical Chinese patent medicine with obvious efficacy and favorable safety, plays a great role in the management of patients with CVDs. Accumulating evid...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.01005
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abstract::Objectives: This study aimed to elucidate the contribution of candidate single nucleotide polymorphisms (SNPs) related to pharmacokinetics on the recovery of platelet function after single dose of ticagrelor was orally administered to healthy Chinese subjects. Methods: The pharmacokinetic profiles of ticagrelor and it...
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doi:10.3389/fphar.2019.00209
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abstract::Purpose: To analyze MiRs expression in serum of UM patients, respect to healthy donors, and to compare this data with MiRs expressed in formalin-fixed, paraffin-embedded UM samples. Methods: Expression profile of 754 miRNAs was performed in serum of patients with uveal melanoma who underwent primary enucleation. The l...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00424
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abstract::Pregnant women appear to be more susceptible to infectious diseases than women in reproductive age. According to the California Department of Public Health pregnant women were 9.6-folds more likely to be hospitalized during the 2009 influenza outbreak when compared to non-pregnant women in reproductive age. In contras...
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abstract::We prepared hybrids consisting of Angelica gigas Nakai (AGN) root or flower extract and layered double hydroxide (LDH) for potential anticancer nanomedicine, as decursin species (DS) in AGN are known to have anticancer activity. Dimethylsulfoxide solvent was determined hybridization reaction media, as it has affinity ...
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doi:10.3389/fphar.2018.00723
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abstract::The cardiac ischemia-reperfusion (I/R) injury greatly influences the therapeutic effect and remains an urgent challenge in clinical therapy. Polypharmacology opens a new therapeutic opportunity to design drugs with a specific target for improving the efficacy. In this study, we first forecasted that Rosmarinic acid (R...
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doi:10.3389/fphar.2017.00456
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abstract::In iron overload disorders a significant fraction of the total iron circulates in the plasma as low molecular weight complexes not bound to transferrin, known as non-transferrin-bound iron (NTBI). By catalyzing the formation of free radicals, NTBI accumulation results in oxidative stress and cellular damage, being a m...
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pub_type: 杂志文章
doi:10.3389/fphar.2014.00024
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abstract::Human peripheral-blood monocytes are used as an established in vitro system for generating macrophages. For several reasons, monocytic cell lines such as THP-1 have been considered as a possible alternative. In view of their distinct developmental origins and phenotypic attributes, we set out to assess the extent to w...
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doi:10.3389/fphar.2018.00071
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abstract::The synthesis, antimicrobial activity evaluations, biomolecule-binding properties (DNA), and absorption and emission properties of a new series of (Z)-1,1,1-trichloro-4-alkyl(aryl)amino-4-arylbut-3-en-2-ones (4, 5) and 2,2-difluoro-3-alkyl(aryl)amino-4-aryl-6-(trichloromethyl)-2H-1,3,2-oxazaborinin-3-ium-2-uides (6, 7...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01328
更新日期:2020-09-02 00:00:00
abstract::Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and remains the most common life-shortening diseases affecting the exocrine organs. The absence of this channel results in an imbalance of ion concentrations across the cell membrane and results in more a...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.01113
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00017
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abstract::Fasudil, a Rho-kinase inhibitor, has shown outstanding therapeutic effects against cerebral vasospasm after subarachnoid hemorrhage (SAH) in humans. Studies show various biological effects of fasudil in the cardiovascular system. We conducted a preclinical systematic review to determine the efficacy and possible mecha...
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2013.00165
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abstract::Classically, the endocannabinoid system (ECS) consists of endogenous lipids, of which the best known are anandamide (AEA) and 2 arachidonoylglycerol (2-AG), their enzyme machinery for synthesis and degradation and their specific receptors, cannabinoid receptor one (CB1) and cannabinoid receptor two (CB2). However, end...
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abstract::Abelmoschus manihot (L.) Medik. (Malvaceae) is a herb used in traditional Chinese medicine to treat some kidney diseases. To date, the detailed mechanisms by which A. manihot improves some kinds of renal disease are not fully understood. In this study, we established Adriamycin-induced NRK-52E cells, the normal rat ki...
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abstract::Thienorphine (TNP) is a novel partial opioid agonist that has completed phase II clinical evaluation as a promising drug candidate for the treatment of opioid dependence. Previous studies have shown that TNP and its glucuronide conjugate (TNP-G) undergo significant bile excretion. The purpose of this study was to inve...
journal_title:Frontiers in pharmacology
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abstract::Objective: Prevalence of osteoporosis in Chinese postmenopausal women has significantly increased over the past decade and oral bisphosphonates are the most potent antiresorptive drugs. The purpose of the present research was to evaluate the cost-effectiveness of oral alendronate for individuals with osteoporosis. We ...
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abstract::Natural products (NPs) are an important source for new drug discovery over the past decades, which have been demonstrated to be effectively used in cancer prevention, treatment, and adjuvant therapy. Many methods, such as the genomic and metabolomic approaches, immunochemistry, mass spectrometry, and chromatography, h...
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abstract::Neonatal hypoxic/ischemic encephalopathy (NHIE) is a severe condition that leads to death or neurological disability in newborns. The underlying pathological mechanisms are unclear, and developing the target neuroprotective strategies are urgent. 2,7,2'-trihydroxy-4,4'7'-trimethoxy-1,1'-biphenanthrene (TTB) is a natur...
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abstract::The root of Aconitum kusnezoffii (Caowu in Chinese, CW) is not only commonly used as a traditional Chinese medicine (TCM), but also served as a tonic in China. Due to its high toxicity, clinical poisoning cases induced by CW have frequently been reported. However, the mechanism is still unclear. In this study, Aconitu...
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abstract::Sustained delivery of analgesic agents at target sites remains a critical issue for effective pain management. The use of nanocarriers has been reported to facilitate effective delivery of these agents to target sites while minimizing systemic toxicity. These include the use of biodegradable liposomal or polymeric car...
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abstract::The serotonin [5-hydroxytryptamine (5-HT)] system has been implicated in the pathogenesis of major depressive disorder (MDD). Among the 5-HT receptor subtypes, 5-HT2 is one of the major pharmacological therapeutic targets for MDD. There have been inconsistent findings in previous pharmacogenetic studies investigating ...
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