tbuckley/cabot-search huggingface dataset:
Prospective evaluation of patients' preferences of three different regimens in a phase II study of FU, oxaliplatin, mitomycin C and CPT-11 in advanced colorectal cancer
Authors: A. Guglielmi, M. Cirillo, S. Mammoliti, G. Fornarini, C. Caroti, A. Sobrero
Journal: Journal of Clinical Oncology (2004)

3757 Background and methods: We evaluated 53 patients with advanced colorectal cancer within a phase II trial of first line CT consisting of 3 sequential parts: a) MTX (days 1 and 15) l-OHP + FU (days 2 and 16) (200, 85 and 600 mg/m2, respectively ) b) three weeks of continuous infusion FU (200 mg/m2/day) from day 29 to 50 along with mitomycin 7 mg m2 on day 29; c) 3 weekly administrations of CPT-11 at the dose of 125 mg/ m2 on days 57, 64, 71. At the end of the 3 segments (3 months = 1 cycle) the patients were asked to rank the tolerability of the different parts. The same question was repeated at each subsequent cycle. Results: Patients characteristics include: median age 63, median ECOG PS 0, colon primary 40, rectal primary 13. Forty-five patients had one metastatic site only and 8 had more than one metastatic site. The median number of cycles administered was two. There were 4 complete and 28 partial responses for an excellent overall response rate of 61 % (95% C.I. = 52%–64% ). Median PFS was 9 months and median OS 20.4 mo. No toxic deaths occurred. The highest toxicity (WHO) was observed during the third part ( CPT-11 alone ) where 13 % diarrhoea and 13 % haematological toxicity grade III were reported. Thirty-six out of 53 patients were asked about their “preference”: the 1st and the 2 nd part of the regimen received the greatest number of preferences, while the 3 rd part ranked last. The remaining 25 % of preferences was distributed between a combination of 1st and 2 nd or 2 nd and 3 rd part(see table). This pattern of distribution was confirmed at the end of the second cycle and correlated with the incidence/intensity of chemotherapy-related toxicity. Conclusions: within a highly active regimen of palliative CT the CPT-11 component appeared not to be as well tolerated as the others, although the timing of data collection might have influenced these results (memory effect). No significant financial relationships to disclose.
Rates of Cortical Atrophy in Adults 80 Years and Older With Superior vs Average Episodic Memory
Authors: Amanda H. Cook, Jaiashre Sridhar, Daniel Ohm, Alfred Rademaker, M.-Marsel Mesulam, Sandra Weintraub, Emily Rogalski
Journal: JAMA (2017)

“SuperAgers” have previously been defined as adults 80 years and older with episodic memory ability at least as good as that of average middle-age adults.1 They have a significantly thicker brain cortex than their same-age peers with average-for-age memory,2 which is unusual as age-related cortical atrophy is considered “normal” and often associated with cognitive decline in nondemented older adults.3 SuperAgers may experience similar atrophy rates as their cognitively average peers but start with larger brain volumes, or they may resist age-related cortical atrophy. To examine the latter possibility, we quantitated rates of cortical volume change over 18 months in SuperAgers and cognitively average elderly adults.
Sequential cisplatin–gemcitabine–docetaxel vs docetaxel–gemcitabine in the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC): Interim results of an ongoing phase II trial
Authors: D. Binder, T. Beinert, H. Schweisfurth, C. Grah, B. Temmesfeld-Wollbrück, G. Müller-Hagen, C. Schäper, D. Schürmann, N. Suttorp
Journal: Journal of Clinical Oncology (2004)

7113 Background: Chemotherapy doublet regimens remain the standard first-line treatment for patients with metastatic NSCLC and good performance status. Three-drug regimens may improve response despite being associated with increased frequencies of adverse events (e.g. neutropenic infections). We conducted a prospective, randomized trial evaluating a sequential 3-drug schedule and a platinum-free chemotherapy doublet. Methods: To date, 91 patients (pts; 110 planned) with stage IV NSCLC (International Union Against Cancer) have been randomized to one of two treatment arms − A: gemcitabine (G) (900mg/m2, 30-minute infusion on days 1 and 8), and docetaxel (D) (75mg/m2, 1-hour infusion on day 1) repeated every 3 weeks for up to 6 cycles; Arm B: G (900mg/m2, days 1 and 8) and cisplatin (70 mg/m2, 1-hour infusion, day 1) were given every 3 weeks for 3 cycles, followed by 3 cycles of D (100 mg/m2, day 1) every 3 weeks. The primary endpoint was survival, secondary endpoints included time to progression, response to treatment, and toxicity. Results: In Arm A (31 pts evaluable) and Arm B (32 pts evaluable), 9 pts (9 partial responses [PR], overall response rate [ORR] 29%) and 11 pts (1 complete response, 10 PR, ORR 34%), respectively responded to treatment according to World Health Organization criteria. Median time to progression was not significantly different between Arm A and B, 105 and 129 days, respectively. Corresponding median survival times were 251 days and 283 days. Frequent adverse events reported in both treatment arms included leukopenia, anemia, nausea/vomiting, alopecia, thrombocytopenia, diarrhea, constipation, and skin toxicity. Febrile neutropenia was present in both arms (2/2 pts), severe vomiting was seen more frequently in the cisplatin-based protocol. Conclusion: In this interim evaluation both schedules demonstrate good activity and acceptable toxicity. No significant financial relationships to disclose.
Faster clean catch urine collection (Quick-Wee method) from infants: randomised controlled trial
Authors: Jonathan Kaufman, Patrick Fitzpatrick, Shidan Tosif, Sandy M Hopper, Susan M Donath, Penelope A Bryant, Franz E Babl
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To determine if a simple stimulation method increases the rate of infant voiding for clean catch urine within five minutes. <b>Design</b>&nbsp;Randomised controlled trial. <b>Setting</b>&nbsp;Emergency department of a tertiary paediatric hospital, Australia. <b>Participants</b>&nbsp;354 infants (aged 1-12 months) requiring urine sample collection as determined by the treating clinician. 10 infants were subsequently excluded. <b>Interventions</b>&nbsp;Infants were randomised to either gentle suprapubic cutaneous stimulation (n=174) using gauze soaked in cold fluid (the Quick-Wee method) or standard clean catch urine with no additional stimulation (n=170), for five minutes. <b>Main outcome measures</b>&nbsp;The primary outcome was voiding of urine within five minutes. Secondary outcomes were successful collection of a urine sample, contamination rate, and parental and clinician satisfaction with the method. <b>Results</b>&nbsp;The Quick-Wee method resulted in a significantly higher rate of voiding within five minutes compared with standard clean catch urine (31% <i>v</i> 12%, P&lt;0.001), difference in proportions 19% favouring Quick-Wee (95% confidence interval for difference 11% to 28%). Quick-Wee had a higher rate of successful urine sample collection (30% <i>v</i> 9%, P&lt;0.001) and greater parental and clinician satisfaction (median 2 <i>v</i> 3 on a 5 point Likert scale, P&lt;0.001). The difference in contamination between Quick-Wee and standard clean catch urine was not significant (27% <i>v</i> 45%, P=0.29). The number needed to treat was 4.7 (95% confidence interval 3.4 to 7.7) to successfully collect one additional urine sample within five minutes using Quick-Wee compared with standard clean catch urine. <b>Conclusions</b>&nbsp;Quick-Wee is a simple cutaneous stimulation method that significantly increases the five minute voiding and success rate of clean catch urine collection. <b>Trial registration</b>&nbsp;Australian New Zealand Clinical Trials Registry ACTRN12615000754549.
Results of a phase 1 clinical trial investigating a combination of the oral mTOR-inhibitor Everolimus (E, RAD001) and Gemcitabine (GEM) in patients (pts) with advanced cancers
Authors: S. Pacey, D. Rea, N. Steven, C. Brock, N. Knowlton, N. Shand, K. Hazell, U. Zoellner, A. O'Donnell, I. Judson
Journal: Journal of Clinical Oncology (2004)

3120 Background: Pre-clinical studies of E have shown dose-dependent inhibition of tumor growth, reduced tumor vascularity and potentiation of the activity of a number of cytotoxics, particularly GEM. This phase 1 study investigated E alone and then in combination with GEM. Initially, pts with advanced, refractory solid tumors were recruited to a dose-escalation study with E given weekly to investigate safety, pharmacokinetics (PK) and optimal biological dose (OBD) as shown by sustained inhibition of the mTOR downstream substrate, S6 kinase 1 in peripheral blood mononuclear cells, comparable to that associated with anti-tumor activity in preclinical models. The OBD was concluded to be 20mg and was well tolerated. Methods: In a new cohort, the OBD was combined with GEM 600mg/m2 given IV, weekly, for 3 weeks in 4-week cycles. Sequential cohorts were planned with incremental doses of 800, and 1,000 mg/m2 to identify the maximum tolerated dose. Results: 8 pts were recruited to an expanded first dose level for the combined schedule (5M:3F; median age 58y, range 46–71y). During the first 28 days, 2/8 pts experienced toxicities (grade 4 neutropenia, grade 3 thrombocytopenia), requiring interruption of GEM according to prescribing recommendations. A further 3/8 developed thrombocytopenia requiring dose reduction. No PK interaction between the drugs was observed in an additional cohort of pts studied at the same dose level. Conclusions: Treatment with GEM, in a standard 4-week cycle at 600mg/m2, a dose lower than usually administered, was not tolerated in a majority of pts receiving E at 20mg/week due to myelosuppression. In the absence of PK interaction it seems likely (in line with pre-clinical data) that the toxicity is the result of combined impact on haemopoiesis. Additional studies with this combination should consider alternative schedules for better tolerability. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Effects of 5-fluorouracil on endothelial nitric oxide synthase in endothelial cells in different states of confluence
Authors: V. M. Casado-Echarren, C. Abarrategui, R. Alvarez, G. Rubio, A. León, M. Dómine, I. Calvo, L. G. Estévez, A. López-Farré, F. Lobo
Journal: Journal of Clinical Oncology (2004)

3149 Background: Some studies suggest a direct effect of 5-fluoruracil (5-FU) on vascular endothelium. The enzyme endothelial nitric-oxide synthase (eNOS) produces nitric oxide (NO) in the endothelium. It is known that NO has multiple physiological functions one of which is involved in the interaction of circulating tumour cells with the endothelium. On the other hand, endothelial cells (E.C) can be found in two different states of proliferation: confluence (quiescent) and subconfluence (proliferating). Our objetives are to study the effect of 5-FU on the eNOS expression and to analyse if there is a direct relationship between the effect of 5-FU and eNOs expression and the state of endothelial growth. Methods: Culture of bovine aortal endothelial cells (B.A.E.C). The dosage of 5-FU was 20 ugr/mL. The enzyme eNOS was measured using Western-blot method. Results: We observed an increase in eNOs expression in subconfluent E.C with respect to confluent E.C (14.6 densitometric units as opposed 8.97 DU;p<0.003; t Student method).The presence of 5-FU reduces eNOS expression in subconfluent E.C with respect to control subconfluent endothelial cells (14.6 DU as opposed to 9.47; p< 0.023). Conclusions: 5-FU reduces eNOs expression in E.C in subconfluence state. This finding suggests a direct effect of 5-FU on the proliferating endothelium and as well a possible effect on tumoral endothelium. No significant financial relationships to disclose.
The effect of oral glutamine supplement (OGS) on fluorouracil (5-FU) induced intestinal mucosal damage (IMD) assessed by intestinal permeability (IP) test
Authors: K. Choi, J. W. Kim, S. J. Oh, W. K. Jeon, S. Y. Kim, S. S. Lee
Journal: Journal of Clinical Oncology (2004)

8050 Background: Systemic chemotherapy may damage gastrointestinal epithelium. IMD and mucositis are one of the most common side effect of chemotherapy. However, there is not a tool for direct measurement of IMD. IMD is associated with increased IP. It is known that IP test with chromium-ethylenediaminetetraacetic acid (51Cr-EDTA) is a useful tool to assess the IMD. Glutamine is the energy source for gastrointestinal epithelium. OGS may have a role in the prevention of chemotherapy induced IMD and mucositis. The aims of this study were to evaluate the relationship between the urinary excretion of 51Cr-EDTA and the severity of IMD and mucositis, and the effect of OGS on 5-FU induced IMD and mucositis. Methods: Fifty one patients with advanced cancer received 5-FU based chemotherapy. Eighteen healthy volunteers were in the control group. IP was assessed by measurement of the urinary excretion of 51Cr-EDTA after oral challenge, on days 6–12 after chemotherapy. Among fifty one patients, twenty two patients received OGS (30 g/day) and twenty nine only best supportive care (BSC). OGS was continued for 15 days. It was started at least three days before chemotherapy. mucositis was graded according to the National Cancer Institute common toxicity criteria. Results: In the chemotherapy group, the mean value of IP test was significantly higher than in the control group (8.68±6.55% vs 1.99±0.53%, respectively, p<0.001). The severity of oral mucositis was correlated with the value of IP test ( p<0.001, r= 0.792). In the OGS group, the mean value of IP test was significantly lower than in the BSC group (5.44±3.42% vs 11.26±7.24%, respectively, p=0.001). In the OGS group, grade II-IV of mucositis was observed in the six patients(10%), and in the eleven patients (38%) in the BSC group. (p<0.001). Conclusions: The IP test may be a useful tool for assessing IMD and mucositis. OGS may have a protective effect on 5-FU based chemotherapy induced IMD and mucositis. Further studies are needed to define the role of OGS in chemotherapy induced IMD and mucositis. No significant financial relationships to disclose.
Eomesodermin promotes the development of type 1 regulatory T (T <sub>R</sub> 1) cells
Authors: Ping Zhang, Jason S. Lee, Kate H. Gartlan, Iona S. Schuster, Iain Comerford, Antiopi Varelias, Md Ashik Ullah, Slavica Vuckovic, Motoko Koyama, Rachel D. Kuns, Kelly R. Locke, Kirrilee J. Beckett, Stuart D. Olver, Luke D. Samson, Marcela Montes de Oca, Fabian de Labastida Rivera, Andrew D. Clouston, Gabrielle T. Belz, Bruce R. Blazar, Kelli P. MacDonald, Shaun R. McColl, Ranjeny Thomas, Christian R. Engwerda, Mariapia A. Degli-Esposti, Axel Kallies, Siok-Keen Tey, Geoffrey R. Hill
Journal: Science Immunology (2017)

Type 1 regulatory T (TR1) cells are Foxp3- interleukin-10 (IL-10)-producing CD4+ T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages. We further show that Eomes induction in TR1 cells requires T-bet and donor macrophage-derived IL-27. Thus, we define the cellular and transcriptional control of TR1 cell differentiation during BMT, opening new avenues to therapeutic manipulation.
Pazopanib (P) and trametinib (T) in advanced cholangiocarcinoma (CC): A phase Ib study.
Authors: Rachna T. Shroff, Ashley O'Connor, Denise Gallagher, Marianna Zahurak, Gary L. Rosner, Chimela Ohaji, Susan Sartorius-Mergenthaler, Ralph Zinner, Nilofer Saba Azad
Journal: Journal of Clinical Oncology (2015)

4072 Background: CC is an aggressive disease with a dismal prognosis and no clear therapy in the refractory setting. Mek inhibition and anti-angiogenic therapies have shown modest activity in advanced CC, while dual inhibition of these pathways has not been evaluated. We investigated the safety of combining of P+T in a phase I trial (previously reported). 2 patients (pts) with CC were enrolled during dose escalation with 1 prolonged partial response (PR) and the other with stable disease (SD). Based on this possible signal, we evaluated the safety and efficacy of this combination in an expansion cohort of 25 advanced, pre-treated CC pts. Methods: P+T were administered daily for a 28-day cycle with radiographic imaging performed every two cycles. Patients were monitored for toxicity throughout. The primary endpoint was progression-free survival (PFS) with secondary endpoints including overall survival (OS), response rate (RR) and disease control rate (DCR, partial response + stable disease). Results: 25 patients were enrolled (median age = 62, 20 evaluable for response). The median follow-up was 8.9 months with pts having received a median number of 2 prior therapies (range 1-9). The most common grade 3/4 toxicities attributable to study drugs included: rash, thrombocytopenia, hypertension, fatigue (all n = 3), and elevated LFT’s (n = 2). ORR was 5% with a DCR of 75% (15/20 pts). Median PFS was 4.3 mths (95% CI: 3.5-7.6) with a 4-mth PFS of 56% (p < 0.002 compared with a pre-specified null hypothesis rate of 25%). Median OS was 6.7 mths. Conclusions: P+T was well tolerated with evidence of activity in refractory CC. Further studies are needed to assess the benefit of combining anti-angiogenic therapy with Mek inhibition and to explore a potential molecular phenotype in which this combination may provide a clinically meaningful benefit. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by GlaxoSmithKline. Clinical trial information: NCT01438554.
Standardized, progressive exercise program (EXCAP) to reduce psychological distress and improve inflammatory cytokines of distress among prostate cancer survivors.
Authors: Charles Stewart Kamen, Michelle Christine Janelsins, Kathi Heffner, Anita Roselyn Peoples, Mohamedtaki Abdulaziz Tejani, Marie Anne Flannery, Luke Joseph Peppone, Gary R. Morrow, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2014)

9510 Background: Psychological distress (a negative emotional, social, or spiritual response to cancer) is among the most common side effects of cancer diagnosis and treatment. Brief and palatable interventions are needed to ameliorate distress in diverse cancer populations, including men with prostate cancer, who may be unwilling to engage in traditional and time-intensive forms of psychotherapy. EXCAP(Exercise for Cancer Patients), a standardized, 6-week, home-based, progressive aerobic and resistance training program, has proven efficacious in improving fatigue among cancer survivors, but its effect on distress and on inflammatory cytokines associated with the pathophysiology of distress are unknown. Methods: In this Phase II RCT, 58 older prostate cancer survivors (age M=67) were randomized either to Arm 1) standard care (control) or Arm 2) EXCAP(intervention). Psychological distress (from the Profile of Mood States) and inflammatory cytokines (IFN-γ, IL-6, IL-8, IL-10, sTNFR-1) were measured at baseline and post-intervention (6 wks later). We used ANCOVA to assess the effect of EXCAPon distress and inflammatory cytokines at post-intervention, controlling for baseline values. We used Pearson correlations to evaluate mechanistic associations between change in distress and change in inflammatory cytokines from pre to post. Results: Among men with prostate cancer, the EXCAPintervention significantly improved psychological distress relative to standard care, as measured by the POMS Total score (EXCAP M=-5.17, SD=14.02; control M=2.43, SD=8.06; F(4,51)=3.34, p=.02). Decreases in distress among EXCAPparticipants were associated with decreases in IFN-γ (r = .40, p = .03) and IL-10 (r = .39, p = .04). This pattern was not seen in the control arm. Conclusions: This study supports the use of EXCAPfor reducing psychological distress and suggests a potential biological mechanism by which this improvement occurs, namely by reducing systemic inflammation. Future, confirmatory research is needed to replicate these findings in larger and diverse samples of cancer survivors. Clinical trial information: NCT00815672.
Comorbidity and survival for patients with advanced-stage non-small cell lung cancer.
Authors: Elizabeth A. Chrischilles, Taher Abu Hejleh, Knute D. Carter, Jane F Pendergast, Thorvardur Ragnar Halfdanarson, Robert H. Fletcher, Robert B Wallace
Journal: Journal of Clinical Oncology (2013)

e19065 Background: Treatment decisions for patients with advanced stage (stages IIIB and IV) non-small cell lung cancer (AS NSCLC) are influenced by comorbidity at time of diagnosis. We studied the effects of comorbidity on survival and whether effects differ for short-term (120 days) vs. for long-term (&gt;120 days) survival. Methods: Data were from surveys and medical records of 1498 patients withnewly diagnosed AS NSCLC in the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS). Respiratory disease severity and comorbidities at diagnosis were measured from the Adult Comorbidity Evaluation (ACE-27) index and model fitting used the Akaike Information Criteria. The log-rank test was used for univariable survival models, and Cox proportional hazards regression for multivariable survival models. Results: Five comorbidities were significantly associated with survival and 437 (29.2%) patients had one or more of these. Survival to 120 days was significantly poorer for patients with a baseline diagnosis of stroke [hazard ratio (HR) 1.92; 95% confidence interval (CI) 1.26–2.93], diabetes (HR 1.33, 95% CI 1.08–1.65), or congestive heart failure (HR 1.45, 95% CI 1.07–1.96), controlling for age, gender, smoking status, stage, severe respiratory disease, and brain metastases. Given survival to 120 days (885 pts, 59%), survival beyond that was significantly poorer only for patients with baseline arrhythmia (HR 1.47, 95% CI 1.15–1.87) or end stage renal disease (HR 1.82, 95% CI 1.09–3.04), controlling for the covariates above. Adjustment for chemotherapy use had no effect on these associations. Conclusions: Several comorbidities present at diagnosis affected survival for AS NSCLC, with some comorbidities having a more immediate relationship to survival than others. Our finding provides information that could be used to tailor treatment decisions to patients’ comorbidities at diagnosis.