Late Trials Research Articles

A retrospective analysis assessing effects of cytotoxic versus cytostatic agents on body mass, nutritional parameters, and performance status in patients with exocrine pancreas cancer enrolled in phase I and II trials.

438 Background: The 5-year survival for pancreatic adenocarcinoma is poor, and patients increasingly turn to experimental agents after conventional treatments have failed. Novel chemotherapeutic agents undergo rigorous phase I and II trials to confirm efficacy, safety, tolerability, and optimal dose for entry into late phase trials. Cytostatic therapies are theorized to have an improved tolerability compared to traditional cytotoxic therapies. Methods: This retrospective study compared the tolerability of cytostatic vs cytotoxic therapies in patients with advanced pancreatic cancer who participated in phase I or II trials at a single institution. Nutrition parameters of weight and albumin, performance status, tumor marker CA 19-9 level, and mean tumor dimension defined by RECIST criteria were obtained for patients within four weeks of trial start date and conclusion. Results: 117 patient trials were assessed in final analysis. No statistically significant difference was observed between patients receiving cytostatic and cytotoxic agents with regards to mean weight loss (1.01 vs 1.30 kg; p =.733), decrease in albumin (0.36 vs 0.29 g/dL; p =.397), and percent change in CA 19-9 (-72% vs -76%; p =.882). Results of change in performance status were similar, with mean increase in ECOG (0.63 vs 0.61; p =.948) and decrease in Karnofsky (13 vs 12, p =.709). There was a statistically significant difference in tumor dimension with cytostatic vs cytotoxic agents (18% vs -3%, p =.043). There were no differences in trends between patients enrolled in one trial compared to those enrolled in multiple trials. Conclusions: This study did not show a significant difference between cytostatic and cytotoxic agents in patients with advanced pancreatic adenocarcinoma in early phase trials with regards to nutritional parameters, performance status, or change in CA 19-9. However, there was a statistically significant change in tumor dimension. Thus, cytotoxic agents have similar tolerability to cytostatic agents and may have additional benefit on tumor burden in patients with advanced pancreatic adenocarcinoma.

Commentary on highlighted late breaking trials in interventional cardiology at ESC, VIVA, TCT, and AHA 2013.

With the plethora of clinical trials, it is difficult for busy interventional cardiologists to stay up to date. Therefore, the SCAI publications committee concisely summarizes and provides editorial commentary on the most important trials from recent, large international meetings. The intent is to provide this summary every six months to allow quick assimilation of trial results into interventional practice. © 2014 Wiley Periodicals, Inc.

Abstract 4260: Standardized decision support in next-generation sequencing (NGS) reports of somatic cancer variants

Abstract Introduction: Of hundreds to thousands of somatic mutations that exist in each cancer genome, a large number are unique and non-recurrent variants. Many such variants occur in tumor genes that have well-established biological and clinical relevance and are putative targets of molecular therapy, however, most variants are still of unknown significance. Prioritizing and reporting genetic variants identified via NGS technologies remains a major challenge. Methods: Based on a systematic framework for cancer variant annotation/prioritization, we propose a structured molecular pathology report using standardized terminology in order to best inform oncology clinical practice. In parallel with the variant interpretation pipeline, we developed a comprehensive knowledge database (Kdb) that integrates tumor types, genes, variants, response/resistance patterns to approved and experimental agents and PubMed identifiers. Results: As physicians rely heavily on limited subsets of data and frequently apply rules based on strength of evidence in the decision-making process, NGS results are presented in a very discrete manner, avoiding detailed descriptions of each genomic aberration. Reportable variants are grouped in three categories: (i) actionable, which support treatment recommendation, enrollment in clinical trials and/or have prognostic or diagnostic implications; (ii) biologically relevant but not clearly actionable, including novel variants lacking functional preclinical validation in known cancer genes; and (iii) variants of unknown significance. Predictive associations are reported according to tumor type and classified in a hierarchical way based on the strength of evidence: (i) late trials; (ii) early trials; (iii) case reports; and (iv) preclinical data being explored in clinical trials. In our internal Kdb, tumor types with the largest number of emerging predictive associations are acute leukemias, non-small cell lung cancer, brain tumors, melanoma, colorectal, ovarian and breast cancers, comprising more than 100 unique gene - drug interactions. Further interpretation of gene variants requires a team with strong background in cancer biology, careful evaluation of the published literature and ability to match a patient's tumor genotype to clinical trials in the context of multiple aberrations. Conclusions: With large amounts of data being generated as high throughput sequencing assays enter the clinical realm, there is a growing need to better communicate relevant findings in a timely manner while remaining cognizant of the potential consequences of misuse or overinterpretation of genomic information. The scientific knowledge on actionable events should be presented the report, so that physicians can make evidence-based decisions and patients may benefit from treatment with matched targeted agents. We hope that our experience in this process will help other institutions implement similar programs. Citation Format: Rodrigo Dienstmann, Fei Dong, Darrell Borger, Dora Dias Santagata, Leif W. Ellisen, Long P. Le, A. John Iafrate. Standardized decision support in next-generation sequencing (NGS) reports of somatic cancer variants. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4260. doi:10.1158/1538-7445.AM2014-4260

The Trial of Jan Hus: Medieval Heresy and Criminal Procedure. By Thomas A. Fudge. New York: Oxford University Press, 2013. xxiii + 392 pp. $74.00 cloth.

(ProQuest: ... denotes non-US-ASCII text omitted.)The Trial of Jan Hus: Medieval Heresy and Criminal Procedure . By Thomas A. Fudge . New York : Oxford University Press , 2013. xxiii + 392 pp. $74.00 cloth.Book Reviews and NotesThe Trial of Jan Hus is the third and last of a series of studies of the Bohemian reformer by Thomas A. Fudge. It seeks to chronicle in careful detail the variety of court proceedings against Hus in the first two decades of the fifteenth century. But this book contains more than narrative; it also quite unapologetically offers judgments, both of Hus and his trial: believe the evidence shows conclusively that Jan Hus was a heretic. I am also convinced that . . . the trial was (347). In reaching these conclusions, Fudge positions himself outside the mainstream of scholarly writings on Hus and the case against him, works which at one point he polemically characterizes as containing little more than the pious longings of their evaluators . . . a projection of their own ideas and desires (346). While this volume's textual analysis is in many ways to be commended, the tone of comments like these mars the overall effectiveness of its argument.In his first three chapters, Fudge begins with a survey of the events leading up to the burning of Hus at the Council of Constance in 1415, as well as with an overview of the procedures that governed late medieval heresy trials. A strength of Fudge's analysis throughout the book is his meticulous examination of the specific provisions of canon law that shaped the church's treatment of Hus. Thus it is no surprise that Fudge treats heresy as primarily a legal category, although he also recounts the ways in which it signified intellectual deviance, religious formation and reform, a challenge to the social order, and a purported form of madness, disease, perversion, and the work of the devil.Chapter 4 initiates Fudge's detailed account of Hus's confrontations with the institutional church, which began in Prague in 1403 with the assembly of a list of Wycliffite articles that unnamed university masters were accused of circulating and affirming. Subsequent chapters trace the evolution of the process against Hus both in Bohemia and at the papal court. Along the way, the reader meets a colorful cast of characters: the sharp Jan Jesenice, Hus's lead attorney for most of the process; Michael de Causis, his primary antagonist; the local archbishop, Zbynek; and participants in the Council of Constance such as Jean Gerson. On Fudge's account, Hus committed significant strategic errors at least twice in the course of the proceedings against him: first by issuing a direct appeal to the judgment of Christ, one that according to Fudge placed him outside the processes of the church and rendered his argument preposterous in the eyes of many; and second by accepting Emperor Sigismund's safe-conduct to attend the Council of Constance. Because Hus had already been excommunicated for heresy at the time of the council and because heretics had no rights in medieval canon law, Fudge argues, the church and its associates were under no legal obligation to honor any promise made to him. …

Testing problem solving in turkey vultures (Cathartes aura) using the string-pulling test.

To examine problem solving in turkey vultures (Cathartes aura), six captive vultures were presented with a string-pulling task, which involved drawing a string up to access food. This test has been used to assess cognition in many bird species. A small piece of meat suspended by a string was attached to a perch. Two birds solved the problem without apparent trial-and-error learning; a third bird solved the problem after observing a successful bird, suggesting that this individual learned from the other vulture. The remaining birds failed to complete the task. The successful birds significantly reduced the time needed to solve the task from early trials compared to late trials, suggesting that they had learned to solve the problem and improved their technique. The successful vultures solved the problem in a novel way: they pulled the string through their beak with their tongue, and may have gathered the string in their crop until the food was in reach. In contrast, ravens, parrots and finches use a stepwise process; they pull the string up, tuck it under foot, and reach down to pull up another length. As scavengers, turkey vultures use their beak for tearing and ripping at carcasses, but possess large, flat, webbed feet that are ill-suited to pulling or grasping. The ability to solve this problem and the novel approach used by the turkey vultures in this study may be a result of the unique evolutionary pressures imposed on this scavenging species.

Commentary on late breaking trials in interventional cardiology at ESC, VIVA, TCT, AHA (Fall 2012), and ACC 2013

With the plethora of clinical trials, it is difficult for busy interventional cardiologists to stay up to date. Therefore, the Society for Cardiovascular Angiography and Interventions (SCAI) publications committee concisely summarized and provided editorial commentary on the most important trials from recent, large international meetings. The intent is to provide this summary every six months to allow quick assimilation of trial results into interventional practice.

Age-related trends of inhibitory control in Stroop-like big–small task in 3 to 12-year-old children and young adults

Inhibitory control is the ability to suppress competing, dominant, automatic, or prepotent cognitive processing at perceptual, intermediate, and output stages. Inhibitory control is a key cognitive function of typical and atypical child development. This study examined age-related trends of Stroop-like interference in 3 to 12-year-old children and young adults by administration of a computerized Stroop-like big–small task with reduced working memory demand. This task used a set of pictures displaying a big and small circle in black and included the same condition and the opposite condition. In the same condition, each participant was instructed to say “big” when viewing the big circle and to say “small” when viewing the small circle. In the opposite condition, each participant was instructed to say “small” when viewing the big circle and to say “big” when viewing the small circle. The opposite condition required participants to inhibit the prepotent response of saying the same, a familiar response to a perceptual stimulus. The results of this study showed that Stroop-like interference decreased markedly in children in terms of error rates and correct response time. There was no deterioration of performance occurring between the early trials and the late trials in the sessions of the day–night task. Moreover, pretest failure rate was relatively low in this study. The Stroop-like big–small task is a useful tool to assess the development of inhibitory control in young children in that the task is easy to understand and has small working memory demand.

Recruitment to trials of late thrombolysis: Lessons from the EXTEND study

To increase the percentage of acute stroke patients benefiting from thrombolysis, the utility of expanding the time window of treatment beyond 4.5hours after stroke onset needs to be investigated. We aimed to identify the target population and the challenges of recruitment of patients for the time window beyond 4.5hours. Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND), a multicentre randomised controlled trial testing the efficacy of thrombolytic therapy in patients with clinically significant ischaemic penumbra between 4.5 to 9hours after stroke onset, was used as a model to evaluate inclusion and exclusion criteria for late thrombolysis trials. Data from all stroke patients admitted to Austin Health over a 1year period were retrospectively analysed. Case notes were examined to determine potential trial eligibility. Of 556 patients assessed, 95 (17%) presented during the EXTEND time window. Sixty-seven of these (70.5%) were wake-up strokes (WUS) and 28 (29.5%) arrived between 4.5 and 9hours after symptoms onset. At least one exclusion criterion was found for 78 (82%) of them. Hence, 17 (3%) patients arrived within an appropriate time frame for the study without any exclusion criteria. Most of these (13) arrived outside routine MRI hours. The number of patients recruited would have increased more than three-fold if imaging had been available 24hours, 7days a week. A significant proportion (17%) of ischaemic stroke patients presented between 4.5 and 9hours after stroke onset. The majority of these were WUS. The major challenge identified for patient recruitment was imaging availability.

How to Calculate Better Our Financial Risk in Oncology?

In the United States, drugs are approved based on criteria of the Food and Drug Administration (FDA). Those criteria are frequently based on the derived survival benefit. However, there is no doubt that our economy is exerting an increasingly greater role in the management of our health care system and the clinical decision making. While the main endpoints of late phase oncology trials are often survivals however drug costs are implicitly vital. Therefore, our vision to achieve an efficient healthcare system must consider combining the results of survival as well as the cost of the drugs in determining whether or not to adopt a therapeutic modality. Such a goal may become feasible if our American health care system explores venues of adopting and adjusting our policies to incorporate positive experiences of certain western European countries.

T lymphocytes targeting native receptors

The adoptive transfer of T cells specific for native tumor antigens (TAs) is an increasingly popular cancer treatment option because of the ability of these cells to discriminate between normal and tumor tissues and the corresponding lack of short or long-term toxicities. Infusions of antigen-specific CD4(+) and CD8(+) T cells targeting viral antigens derived from Epstein-Barr virus (EBV) induce sustained complete tumor remissions in patients with highly immunogenic tumors such as post-transplant lymphoproliferative disease, although resistance occurred when the infused T-cell population had restricted antigen specificity. T cells specific for EBV antigens have also produced complete remissions of EBV-positive nasopharyngeal carcinomas and lymphomas developing in immunocompetent individuals, even though in these patients tumor survival is dependent on their ability to evade T-cell immunity. Adapting this strategy to non-viral tumors is more challenging, as the target antigens expressed are less immunogenic and the tumors lack the potent danger signals that are characteristic of viruses. The goals of current studies are to define conditions that promote expansion of antigen-specific T cells ex vivo and to ensure their in vivo persistence and survival by combining with maneuvers such as lymphodepletion, checkpoint inhibition, cytokine infusions, or genetic manipulations. More pragmatic goals are to streamline manufacturing to facilitate the transition of these therapies to late phase trials and to evaluate closely histocompatibility antigen (HLA)-matched banked antigen-specific T cells so that T-cell therapies can be made more broadly available.

Memory under pressure: Secondary-task effects on contextual cueing of visual search

Repeated display configurations improve visual search. Recently, the question has arisen whether this contextual cueing effect (Chun & Jiang, 1998) is itself mediated by attention, both in terms of selectivity and processing resources deployed. While it is accepted that selective attention modulates contextual cueing (Jiang & Leung, 2005), there is an ongoing debate whether the cueing effect is affected by a secondary working memory (WM) task, specifically at which stage WM influences the cueing effect: the acquisition of configural associations (e.g., Travis, Mattingley, & Dux, 2013) versus the expression of learned associations (e.g., Manginelli, Langer, Klose, & Pollmann, 2013). The present study re-investigated this issue. Observers performed a visual search in combination with a spatial WM task. The latter was applied on either early or late search trials--so as to examine whether WM load hampers the acquisition of or retrieval from contextual memory. Additionally, the WM and search tasks were performed either temporally in parallel or in succession--so as to permit the effects of spatial WM load to be dissociated from those of executive load. The secondary WM task was found to affect cueing in late, but not early, experimental trials--though only when the search and WM tasks were performed in parallel. This pattern suggests that contextual cueing involves a spatial WM resource, with spatial WM providing a workspace linking the current search array with configural long-term memory; as a result, occupying this workspace by a secondary WM task hampers the expression of learned configural associations.

Frovatriptan in the treatment of menstrually related migraine: Evidence from late trials and current recommendations

Frovatriptan in the treatment of menstrually related migraine: Evidence from late trials and current recommendations

Verbal Implicit Sequence Learning in Persons Who Stutter and Persons With Parkinson's Disease

ABSTRACTThe authors investigated the integrity of implicit learning systems in 14 persons with Parkinson's disease (PPD), 14 persons who stutter (PWS), and 14 control participants. In a 120-min session participants completed a verbal serial reaction time task, naming aloud 4 syllables in response to 4 visual stimuli. Unbeknownst to participants, the syllables formed a repeating 8-item sequence. PWS and PPD demonstrated slower reaction times for early but not late learning trials relative to controls reflecting delays but not deficiencies in general learning. PPD also demonstrated less accuracy in general learning relative to controls. All groups demonstrated similar limited explicit sequence knowledge. Both PWS and PPD demonstrated significantly less implicit sequence learning relative to controls, suggesting that stuttering may be associated with compromised functional integrity of the cortico-striato-thalamo-cortical loop.

Choice of Baseline in Parallel Thorough QT Studies

Although the ICH E14 Guidance [1] was adopted in 2005 there is still much debate on the appropriate baseline needed to adjust for the variable nature of the QT interval and its heart rate corrected value (QTc) in the parallel Thorough QT (TQT) study. Numerous reports have documented the influence of circadian rhythm [2], food ingestion [3], sleep [4], and autonomic tone [5] on the QT/QTc interval. In the absence of baseline measurements, these factors can make it difficult to interpret QT effects of the study drug. In this issue of Drug Safety Dr. Zhang and colleagues [6] advocate the use of a time-matched baseline in parallel TQT studies to maximize the precision and accuracy of point estimates for QTc effects. Their recommendation is based on analyses of commonly used baseline correction methods using a large data set of parallel TQT studies submitted to the FDA for statistical review by sponsors. One assumption in the choice of baseline is that it should have no influence on the magnitude of QT effects (high accuracy) and it should minimize the uncertainty of the effects (high precision). Both accuracy and precision are important for the interpretation of a TQT trial. As a result, there is much focus on the implications of using different baseline adjustments in the parallel TQT study and understanding the role each baseline definition can have in determining the outcome of the trial as either positive or negative. The distinction between a positive or negative TQT study is based on the upper bound of the 95 % one-sided confidence interval (CI) for the largest time-matched mean difference in QTc between drug and placebo (baseline adjusted). If these (double-delta) DDQTc values exclude 10 ms at all study times the result is a negative TQT study [1]. Intensive ECG monitoring is then hardly ever required in subsequent trials (phase II/III). Conversely, drugs for which an effect exceeding 10 ms cannot be excluded almost always require additional QT interval monitoring in target patients including dose-concentration effects, outlier analysis, changes in mean QTc values, analysis of QTc in subgroups of interest, and identification of individuals who develop a markedly prolonged QTc. The need for additional ECG monitoring in late phase trials can add millions to drug development and may ultimately pose financial limitations on the number of medications which can be developed [7]. The importance of correctly adjusting for baseline in the TQT study is therefore evident.

Novelties in gout

Chronic asymptomatic hyperuratemia (HUA), gout paroxysm in patients with chronic hyperuratemia (HU) and normouricemic attacks of gouty arthritis are well known, but poorly understood. A review of the current literature with attempt of its explanation is presented. The natural course of gout is associated with joint structure changes that may be evaluated by different imaging techniques; comparative advantages and shortcomings of each technique are presented. For almost over 50 years the market has not offered new drugs for the control of HU and gout, while management of such patients was a rather neglected field. Over the last five years an unpredictable number of prospective clinical studies have been conducted involving the investigation of the efficacy and safety of new drugs to control HU (febuxostat, pegloticase). The return of pharmaceutical industry into the world of gout has considerably changed the picture. New recommendations have been presented on appropriate colchicine dose regime for acute gouty flares. Emerging therapies, including pegloticase, uricosuric agent RDEA596 and the interleukin-1 inhibitors have shown promises in early and late phase clinical trials. Each of them deserves to be considered for implementation and feasibility in clinical practice as well as outcome measures for clinical trials. Another purpose of this review was to summarize new knowledge on approved drugs to treat hyperuricemia, or the clinical manifestations of gout. Results of several clinical trials provide new data on the efficacy and safety of the approved urate lowering drugs (allopurinol and febuxostat). Lifestyle and dietary recommendations for gout patients should take into consideration overall health benefits and risks, since gout is often associated with metabolic syndrome and an increased future risk of cardiovascular disease and mortality. This review also summarizes the recent data about lifestyle factors that influence serum uric acid levels and the gout risk, and attempts to provide holistic recommendations, considering both their impact on gout as well as on other health implications.

Young Adults at Risk for Stimulant Dependence Show Reward Dysfunction During Reinforcement-Based Decision Making

While stimulant-dependent individuals continue to make risky decisions, in spite of poor outcomes, much less is known about decision-making characteristics of occasional stimulant users (OSU) at risk for developing stimulant dependence. This study examines whether OSU exhibit inefficient learning and execution of reinforced decision-outcome contingencies. Occasional stimulant users (n = 161) and stimulant-naïve comparison subjects (CTL) (n = 48) performed a Paper Scissors Rock task during functional magnetic resonance imaging. Selecting a particular option was associated with a predetermined probability of winning, which was altered repeatedly to examine neural and behavioral characteristics of reinforced contingencies. Occasional stimulant users displayed greater anterior insula, inferior frontal gyrus, and dorsal striatum activation than CTL during late trials when contingencies were familiar (as opposed to being learned) in the presence of comparable behavioral performance in both groups. Follow-up analyses demonstrated that during late trials: 1) OSU with high cannabis use displayed greater activation in these brain regions than CTL, whereas OSU with low cannabis use did not differ from the other two groups; and 2) OSU preferring cocaine exhibited greater anterior insula, inferior frontal gyrus, and dorsal striatum activation than CTL and also displayed higher activation in the former two regions than OSU who preferred prescription stimulants. Occasional stimulant users exhibit inefficient resource allocation during the execution of reinforced contingencies that may be a result of additive effects of cocaine and cannabis use. A critical next step is to establish whether this inefficiency predicts transition to stimulant dependence.

Invited Commentary

Invited Commentary

A mismatch between methods and objectives in phase I drug development: Statistical limitations and personalized medicine—A California Cancer Consortium (CCC) study.

2538 Background: Patient variation in drug response and toxicity impacts all phases of drug development. While detailed sample-size calculations and analysis based on statistical methodology are critical for addressing variation in late stage trials, phase I studies pose unique and largely unsolved challenges related to variability. Changes in patient selection during the study, small sample-sizes and large patient variation in toxicity are exactly the kind of problems that statistical methods cannot address in small, isolated phase I studies, regardless of apparent mathematical rigor. We have documented these problems via a physician survey. Methods: A 10-question anonymous survey was sent to 670 oncologists at National Comprehensive Cancer Network (NCCN) and CCC institutions via an online survey. 19 % (126/670) of the oncologists polled responded. 78/126 (62%) specialized in Medical Oncology. The number of years in practice varied from 2-45 yrs with a median of 17 yrs. Results: a) 66% of all respondents stated that non-DLT toxicities on one dose level would impact their patient selection on the following dose level, conflicting with the assumption of random patient selection implicit in simulations used in evaluating statistical designs. b) Only 13% stated a desire to target a non-heme toxicity as high as 20% grade 3, while 87% desired a 10% or less grade 3 rate; c) More than half the respondents would prefer not to escalate if 3/3 patients experienced grade 2 LFTs; d) 82% of the respondents thought the appropriate target toxicity differed for patients depending on their potential for becoming a surgical candidate, furthering the need for personalized dosing. Conclusions: Statistical methods in phase I trials are unable to address many of the salient features of phase I study conduct and investigator goals. We will present several approaches we have initiated to address these limitations, and present future plans to help produce a more reliable estimate of a recommended dose. Supported in part by NCI grants U01CA062505, N01-CM-62209, and NCCN data collection assistance.

Considering the changing landscape of heart failure care

British Journal of Cardiac NursingVol. 7, No. 4 Meeting ReportConsidering the changing landscape of heart failure careJayne Masters, Suzy Hughes, Jane ButlerJayne MastersSearch for more papers by this author, Suzy HughesSearch for more papers by this author, Jane ButlerSearch for more papers by this authorJayne Masters; Suzy Hughes; Jane ButlerPublished Online:27 Sep 2013https://doi.org/10.12968/bjca.2012.7.4.194AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Anker S, Colet J, Filipatos M et al. for the FAIR-HF trial investigators (2009) Ferric Carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 361: 2436–2436 Crossref, Google ScholarHjalmarson A (2007) Controlled Rosuvastatin multinational trial in heart failure (CORONA) – results of an outcomes trial in patients with ischaemic heart disease and heart failure. American heart association 2007. Scientific session; November 5 2007; Orlando Fl Late breaking trials Google ScholarNational Institute for Cardiovascular Outcomes Research (2011) National Heart Failure Audit April 2010–March 2011. http://www.ucl.ac.uk/nicor/audits/heartfailure/additionalfiles/pdfs/annualre-ports/annual11.pdf (accessed 23 March 2012) Google ScholarTavazzi L, Maggioni AP, Machioli R et al. for the Gissi -HF trial investigators (2008) Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised double blind, placebo controlled trial. Lancet 372: 1231–1231 Crossref, Google ScholarWyse DG, Waldo AL, DiMarco JP et al. (2002) A comparison of rate control and rhythm control in patients with atrial fibrillation. The atrial fibrillation follow up investigation of rhythm management (AFFIRM) investigators. N Engl J Med 347: 1825–1825 Crossref, Google Scholar FiguresReferencesRelatedDetails 1 April 2012Volume 7Issue 4ISSN (online): 2052-2207 Metrics History Published online 27 September 2013 Published in print 1 April 2012 Information© MA Healthcare LimitedPDF download

A case of metastatic urachal adenocarcinoma treated with several different chemotherapeutic regimens.

Urachal cancer is a rare form of bladder cancer that arises from the urachus, a vestigial musculofibrous band that extends from the dome of the bladder to the umbilicus. Urachal cancer often presents at an advanced stage and has a dismal prognosis. We present a case of a young woman with urachal cancer that recurred rapidly post-partial cystectomy. The patient was treated with up to 6 different chemotherapy regimens, including an oral antiangiogenic drug as part of a clinical trial. Our case illustrates the aggressive nature of this disease, the difficulty in accessing drugs for the treatment of rare cancers and the lack of late stage clinical trials to help guide therapeutic decisions.