tbuckley/cabot-search huggingface dataset:
Second line chemotherapy with topotecan and gemcitabine in small cell lung cancer (SCLC) patients: An Alpe-Adria Thoracic Oncology Multidisciplinary group phase II study (ATOM 012)
Authors: O. Belvedere, C. Sacco, A. Ardizzoni, C. Rossetto, A. Follador, A. Sibau, S. Tumolo, C. Defferrari, G. Fasola, F. Grossi
Journal: Journal of Clinical Oncology (2006)

17014 Background: Topotecan is the only single agent currently approved for the treatment of relapsed or recurrent SCLC, showing activity both in chemotherapy-refractory (RR 2–14%) and in chemotherapy-sensitive patients (RR 14–38%). The role of topotecan in combination with other active agents is still under investigation. Methods: Aim of this phase II study is to assess the activity and safety of topotecan (1mg/sqm iv d1–5) plus gemcitabine (1250 mg/sqm iv d1) in relapsed or recurrent SCLC patients. Treatment is repeated every 4 weeks, up to a maximum of 6 cycles. Eligibility criteria: histologically or cytologically confirmed SCLC; documented progressive disease after ≥ 1 chemotherapy regimen; age ≥ 18 yrs; ECOG PS 0–2; measurable disease (RECIST); no prior treatment with topotecan or gemcitabine; adequate hematologic, hepatic and renal function; brain metastases are allowed. Results: A total of 44 patients have been enrolled. Patient characteristics are as follows: median age, 64 yrs (range 35–77); male/female, 35/9; ECOG PS 0/1/2, 12/21/11 patients; 68% patients had sensitive disease (recurrence &gt; 3 months after first-line chemotherapy) and 32% patients had refractory disease (failure ≤3 months after first-line chemotherapy). One-hundred and seventeen chemotherapy courses have been administered (median 2, range 1–6). The following preliminary results refer to 37 patients. Grade 3–4 toxicities: 54% neutropenia, 16% anemia, 46% thrombocytopenia, 13% neutropenic fever, 27% fatigue. One toxic death was observed. Objective responses have been documented in 9 patients, for an overall response rate of 24% (3% CR, 21% PR); SD was observed in 7 patients (19%), PD in 17 patients (46%). Four early deaths were reported. Median time to progression is 8.9 weeks. Median survival time is 16.3 weeks, and 1-year survival rate is 14%. Conclusions: Based on these preliminary results, the combination of topotecan plus gemcitabine shows moderate activity and an acceptable toxicity profile in previously treated SCLC patients. However, it is unlikely that the addition of gemcitabine improves the outcome compared to single agent topotecan. No significant financial relationships to disclose.
Correlation between severity of acute wheezing episodes and atopic status
Authors: Felicia Cora, Eugenia Buzoianu, Mariana Moiceanu, Doina Anca Plesca
Journal: European Respiratory Journal (2013)

Background: Differentiating early asthma exacerbations from viral wheezing episodes and future asthmatic children from transient wheezers is difficult in young children.  Asthma predictive index (API) is a useful tool to detect children who are likely to become asthmatic later in life by putting emphasis on the atopic status.  The aim of this study is to test the hypothesis that increased severity of acute wheezing episodes in young children can be used as a predictor for atopic status and also for predicting a future asthmatic child.  Method: A retrospective study was conducted including 83 boys with recurrent wheezing aged  10) included 39 boys. Prevalence of positive API was determined for each group.  Results: Prevalence of positive API in the first group was 27,27% (12 boys) and in the second group 28,21% (11 boys). The difference between the 2 prevalences is not statistically significant (p=1).  Conclusion: In young children acute wheezing episodes with increased severity cannot be considered predictors for atopic status and for future asthma.
Randomized clinical trial: The Impact of Medical Qigong (traditional Chinese medicine) on fatigue, quality of life, side effects, mood status and inflammation of cancer patients
Authors: B. Oh, P. Butow, B. Mullan, S. J. Clarke, P. Beale, D. Rosenthal
Journal: Journal of Clinical Oncology (2008)

9565 Background: The quality of life (QOL) of cancer patients is often diminished due to the side effects of treatment and symptoms of the disease itself. Medical Qigong (MQ), coordination of gentle exercise and relaxation through meditation and breathing exercise based on the Chinese Medicine theory of energy channels, may improve health and mental wellbeing and reduce the symptoms of cancer patients. However, there have been few studies of MQ in the cancer setting, and none exploring its impact in a randomized clinical trial (RCT) on QOL, side effects (including fatigue), mood status and inflammation. This was a pilot study preceding a full RCT of this intervention. Methods: Forty-three patients diagnosed with a range of cancers, were randomly assigned to two groups: a control group (n=21) that received usual health care and an intervention group (n=22) who participated in a MQ program for 10 weeks in addition to receiving usual health care at the hospital. Randomization was stratified by completion of cancer treatment (n=20) or under active cancer treatment (n=23). Patients completed measures before and after the program. Cancer related fatigue was measured by FACT-F, quality of life and symptoms were measured by the FACT-G, mood status by POMS. The inflammatory marker serum C-reactive protein (CRP) was also monitored serially. Results: The Medical Qigong intervention group reported clinically significantly improved fatigue (t30 =2.67, p=0.012, mean difference=5.9) and overall QOL (t30 =1.22, p=0.017, mean difference =10.2) compared to the control group. Analysis of the FACT- G subscales revealed that satisfaction with sex life (t12 =2.38, p=0.035) was significantly higher in the MQ group. The MQ intervention also reduced side effects (nausea, pain and insomnia), mood and inflammation biomarker (CRP) but these differences were not statistically significant compared to the control group. Conclusions: Data from the study suggests that MQ with usual health care can improve fatigue, satisfaction with sex life and QOL in cancer patients. This pilot study supports the use of MQ as an intervention for cancer patients. However, further research with a larger sample size is needed. No significant financial relationships to disclose.
Extrapulmonary findings detected in a low-dose spiral computed tomography (sCT) early detection study for lung cancer (LC)
Authors: U. Ricardi, S. Novello, L. Cardinale, B. Crida, F. Perotto, P. Sperone, P. Borasio, M. Giajlevra, G. Selvaggi, G. V. Scagliotti
Journal: Journal of Clinical Oncology (2006)

7206 Background: In 2001 a feasibility study testing low-dose sCT as an early diagnosis tool in asymptomatic volunteers at high risk for lung cancer was planned and initiated at our institution with an evaluation at baseline and then annually for 5 years. Subjects &amp; Methods: We enrolled 520 asymptomatic volunteers, 73% males, aged 55 years or older (median age 60 yrs), with at least 20 pack-years of cigarette smoking and no previous cancer. Results: At baseline, one hundred forty-four extra-pulmonary findings (28%) were detected. The more common findings were: radiologically-detected adrenal enlargements (19%); thyroid struma (8%); hepatic abnormalities, like angiomas, cysts, calcifications, steatosis (29%); renal alterations, like cysts, lithiasis, vascular calcifications and one case of stage I renal carcinoma (21%); spleen abnormalities, like cysts, calcifications, accessory spleen (5%); cholelithiasis (4%); pancreatic alterations (1%); thymic nodules (1%); axillary adenopathy (5%); aortic ectasia or aneurysm (5%) and one breast nodule. In 2 cases (renal carcinoma and breast nodule) a surgical resection was performed. All these findings were followed up through a letter to the general practitioner. In 62 subjects the initial findings were considered worth of further imaging investigations or were suggestive for a clinically definite disease (e.g. renal carcinoma). In the remaining 82, mainly based on personal history data, the abnormalities were already known and previously diagnosed. Globally, the cumulative number of extrapulmonary findings from 2nd to 5th year was 275 and the more common findings were: cysts (hepatic 9%, renal 13%), lithiasis (renal 1%, hepatic 5%), thyroid struma 4%, adrenal adenomas 3%, vascular calcifications 37%, aneurysm 3%, vertebral artropathy 2%. Conclusions: Even if early detection of lung cancer will result in a survival benefit, in the cost-effectiveness analyses the additional costs from the detection of extra-pulmonary findings should also be carefully considered because in many cases they may request substantial outpatient clinic admissions and further diagnostic investigations. No significant financial relationships to disclose.
Phase II trial of depsipeptide (NSC-630176) in colorectal cancer patients who have received either one or two prior chemotherapy regimens for metastatic or locally advanced, unresectable disease: A Southwest Oncology Group study
Authors: R. P. Whitehead, S. McCoy, I. S. Wollner, L. Wong, W. G. Harker, P. M. Hoff, P. J. Gold, K. G. Billingsley, C. D. Blanke
Journal: Journal of Clinical Oncology (2006)

3598 The treatment for metastatic colorectal cancer has markedly improved but the disease is still not curable, and additional active agents need to be found. Depsipeptide is a histone deacetylase inhibitor that has shown activity against human solid tumor cell lines and promising results in murine model systems. This phase II trial was undertaken to determine its activity in patients with advanced colorectal cancer. Eligibility requirements included measurable disease, either metastatic or locally advanced and not surgically resectable, Zubrod performance status of 0–1, and adequate renal, hepatic, hematologic and cardiac function. Prior surgery or radiation therapy was allowed and patients were required to have received either one or two prior chemotherapy regimens for advanced disease. A two-stage design was used designed to detect a difference in the null hypothesis of 5% response vs. an alternative 20% response, with 20 eligible patients to be accrued initially followed by an additional 20 patients if one or more confirmed responses were observed. The study closed after the first stage, with 28 patients registered. Three patients are ineligible, two who did not meet requirements for serum magnesium level, and one whose baseline labs were performed more than 14 days prior to registration. One eligible patient never received treatment and is not analyzable for any endpoint. For the 24 eligible and analyzable patients, median age was 58.6 years (range 31–84) with 14 males. Performance status was 0 in 16 patients and 1 in 8. Ten patients received 1 prior chemotherapy regimen and 14 received 2 prior regimens. There were no grade 4 or higher toxicities. The most common grade 2 or 3 toxicities were anorexia, fatigue, nausea, and dehydration. No objective responses were observed. Four patients had stable disease, 15 showed increasing disease, 3 had symptomatic deterioration, and 2 had assessment inadequate. The current Kaplan-Meier estimate of 6 month overall survival is 69% (95% CI 50%-88%) with a median survival of 8.4 months. Depsipeptide does not show significant anti-tumor activity in previously treated patients with advanced colorectal cancer. No significant financial relationships to disclose.
Phase I Trial of 6-Hour Infusion of Glufosfamide, a New Alkylating Agent With Potentially Enhanced Selectivity for Tumors That Overexpress Transmembrane Glucose Transporters: A Study of the European Organization for Research and Treatment of Cancer Early Clinical Studies Group
Authors: Evangelos Briasoulis, Ian Judson, Nicholas Pavlidis, Philip Beale, Jantien Wanders, Yvonne Groot, Gijbert Veerman, Martina Schuessler, Georg Niebch, Konstantinos Siamopoulos, Eleftheria Tzamakou, Dimitra Rammou, Lisa Wolf, Ruth Walker, Axel Hanauske
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the maximum-tolerated dose (MTD), the principal toxicities, and the pharmacokinetics of 6-hour infusion of glufosfamide (beta-d-glucosylisophosphoramide mustard; D-19575), a novel alkylating agent with the potential to target the glucose transporter system. PATIENTS AND METHODS: Twenty-one patients (10 women and 11 men; median age, 56 years) with refractory solid tumors were treated with doses ranging from 800 to 6,000 mg/m 2 . Glufosfamide was administered every 3 weeks as a two-step (fast/slow) intravenous infusion over a 6-hour period. All patients underwent pharmacokinetic sampling at the first course. RESULTS: The MTD was 6,000 mg/m 2 . At this dose, two of six patients developed a reversible, dose-limiting renal tubular acidosis and a slight increase in serum creatinine the week after the second and third courses of treatment, respectively, whereas three of six patients experienced short-lived grade 4 neutropenia/leukopenia. Other side effects were generally mild. Pharmacokinetics indicated linearity of area under the time–versus-concentration curve against dose over the dose range studied and a short elimination half-life. There was clear evidence of antitumor activity, with a long-lasting complete response of an advanced pancreatic adenocarcinoma and minor tumor shrinkage of two refractory colon carcinomas and one heavily pretreated breast cancer. CONCLUSION: The principal toxicity of 6-hour infusion of glufosfamide is reversible renal tubular acidosis, the MTD is 6,000 mg/m 2 , and the recommended phase II dose is 4,500 mg/m 2 . Close monitoring of serum potassium and creatinine levels is suggested for patients receiving glufosfamide for early detection of possible renal toxicity. Evidence of antitumor activity in resistant carcinomas warrants further clinical exploration of glufosfamide in phase II studies.
Response to Letters Regarding Article, “Renal Dysfunction Is Associated With a Reduced Contribution of Nitric Oxide and Enhanced Vasoconstriction After a Congenital Renal Mass Reduction in Sheep”
Authors: Kate M. Denton, Yugeesh R. Lankadeva, Reetu R. Singh, Helena C. Parkington, Marianne Tare, Karen M. Moritz
Journal: Circulation (2015)
Somatic copy number abnormalities (SCNAs) and mutations in PI3K/AKT pathway as prognostic factors for overall survival (OS) in platinum-treated locally advanced or metastatic urothelial tumors.
Authors: Joaquim Bellmunt, Lillian Werner, Jeffrey J. Leow, Stephanie A. Mullane, Markus Riester, Paul Van Hummelen, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2014)

4511 Background: An integrative analysis was conducted to identify genomic alterations and mutational status on the gene pathway level that could predict OS in pts with urothelial cancers (UC) treated with platinum chemotherapy. Methods: DNA was extracted from FFPE samples from invasive UC and screened for mutations and CNAs. Of those, complete clinical data was available from 85 pts. Mutations were analyzed by a mass-spectrometry based genotyping platform (Oncomap v3) and genomic imbalances were detected by comparative genomic hybridization (CGH) analysis. Regions with threshold of log2 ratio ≥0.4, or ≤ -0.3 were defined as either having copy number gain or loss with significant CNAs determined using a GISTIC analysis.To better define the co-occurrence pattern of mutations and CNAs, we grouped genes into 3 core signal transduction pathways: 1) TP53 pathway; 2) RTK-RAS-RAF pathway including ERBB2, FGFR3, MET, FGFR1, KRAS BRAF, RAF1 and NF1; 3) PI3K/AKT pathway including PTEN, PIK3CA, AKT1, TSC1 and MTOR. OS was measured from treatment to time of death or censored. Cox regression was used to assess pathways abnormalities and mutations with outcome. Results: 35 out of 94 samples (41%) platinum treated pts with advanced UT, harbored mutations on at least 1 gene, mainly TP53 (16%), PIK3CA (9%), FGFR3 (2%), HRAS/KRAS (5%) and CTNNB1 (1%). 66%of pts had some sort of CNA. PI3K/AKT was the most affected pathway and was associated with shorter overall survival (hazard ratio (HR) 2.3, 95% CI: 1.3-4.2). There was no significant association between mutational status and OS. PIK3CA/AKT pathway alteration (mutations +CNV) may have the greatest impact on OS (p=0.055). Over-expression of CTNNB1 (p=0.0008) and PIK3CA (p=0.02) was associated with decreased OS. Among other individual genomic alterations, TP53 mutations (p=0.07) ,mTOR gain (p=0.07) and PTEN over expression (p=0.08) were marginally significant negative impact on OS. Conclusions: Our results suggest that targeted therapies focusing on the PIK3CA pathway alterations can generate the greatest impact in the overall patient population of metastatic UC.
SWOG S0102: A phase II study of docetaxel (DOC) and vinorelbine (VNR) + filgrastim for HER-2 negative, stage IV breast cancer
Authors: J. Gralow, S. Green, D. Lew, W. Barlow, K. Dammann, G. Somlo, S. Rivkin, S. Taylor, L. Wong, R. Livingston
Journal: Journal of Clinical Oncology (2005)

567 Background: The taxane DOC and the vinca alkaloid VNR have demonstrated significant single agent activity in breast cancer. Preclinical studies suggest potential synergy between these two classes of anti-tubulin chemotherapy. This study evaluates both agents in combination as first-line chemotherapy for stage IV breast cancer. Methods: Patients with HER-2 negative, metastatic breast cancer without prior chemotherapy for stage IV disease or prior taxane in any setting were eligible. DOC (60 mg/m2) was given intravenously on Day 1 and VNR (27.5 mg/m2) intravenously on Days 8 and 15 of a 21-day cycle. Filgrastim was given days 2–21. The primary study outcome was overall survival at 1-year, with secondary outcomes of progression-free survival (PFS), response rate (RR), and toxicity. The planned sample size was 90 patients, sufficient to estimate 1-year survival within 11% at α=0.05 (2-sided). Results: A total of 95 patients were registered between 5/01 and 1/04, with 92 eligible for analysis. Four patients are still on treatment, with the most common reasons for discontinuation being progression/relapse/death (47%) and adverse events (25%). Survival at 1-year is estimated to be 73% (95% CI 63%–82%) with a median survival of 19.3 months (95% CI 17.3–28.4). One-year PFS is 34% (95% CI 24–43%) with median PFS of 7.9 months (95% CI 6.5–10.3). Of 70 patients assessable for response, the RR is 46%. Grade 3 and 4 adverse events were 46% and 16%, respectively. There were 3 deaths judged possibly related to treatment, 1 due to sepsis and 2 due to respiratory infections. Grade 4 neutropenia was 12%, febrile neutropenia rate was 3%. The most common grade 3/4 non-hematologic toxicities were fatigue (12%), pneumonitis (10%) and dyspnea (9%). Discussion: The combination of DOC and VNR is very active as first-line chemotherapy in HER-2 negative, stage IV breast cancer. A companion study for HER-2 positive patients with the addition of trastuzumab to this combination (S0215) is ongoing. Important biological correlative studies evaluating predictors of response to anti-tubulin agents are also underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Aventis, GlaxoSmithKline Amgen, Aventis, GlaxoSmithKline
Pharmacokinetics of 5-fluorouracil in colorectal cancer patients receiving interferon
Authors: K Pittman, T Perren, U Ward, J Primrose, M Slevin, N Patel, P Selby
Journal: Annals of Oncology (1993)

The outlook for patients with advanced colorectal cancer remains poor. Recent reports of the combination of 5-fluorouracil (5-FU) and alpha-interferon in colorectal cancer have suggested better response rates. One possible explanation for interaction between 5-FU and interferon is that interferon alters the pharmacokinetics of 5-FU, increasing plasma 5-FU levels.To investigate the possibility of interaction between the two agents, steady state 5-FU pharmacokinetics was evaluated in patients with colorectal cancer who received 5-FU by continuous i.v. infusion with and without concurrent administration of subcutaneous alpha-interferon. 5-FU levels were measured by reverse-phase high-performance liquid chromatography.Twenty-six patients were evaluated. There were 4 partial responses (15%). There was no significant difference in steady state 5-FU levels whether or not alpha-interferon was administered concurrently.Any synergistic activity that may exist between this combination of 5-FU and alpha-interferon is not simply due to altered 5-FU pharmacokinetics.
Abstract 340: Cardiac Autonomic Activity, Cardiac Function and Arrhythmogenic Property in Heart in Hemorrhagic Shock: Effect of Artificial Oxygen Carrier
Authors: Bonpei Takase, Yoshihiro Tanaka
Journal: Circulation (2014)

Lethal ventricular arrhythmias (VT/VF) is serious complications in severe hemorrhagic shock (HS). Cardiac autonomic imbalance and dysfunction are well known unfavorable conditions. However, the effect of oxygenation including artificial oxygen carrier is not fully understood. To investigate the role of oxygenation in lethal HS, cardiac autonomic activity measures, cardiac function test, optical mapping analysis (OMP), and electrophysiological study (EPS) were performed in rats lethal HS. Methods and Results: 1) Over the course of 150 min, rats were subjected to blood withdrawal (0.2 mL/min; total 85% bleeding) and simultaneously transfused with washed rat red blood cells (wRBC), liposome-encapsulated hemoglobin (LHb) or 5% albumin (5%ALB). Temporal changes in cardiac function by 2-D Echocardiography, heart-type fatty acid-binding protein (hFAB) levels, plasma levels of catecholamines, heart rate variability (HRV), and hypoxia-inducible factor 1α expression (HIF1) were measured. As results, &gt; 85% of the rats transfused with either LHb or wRBC survived for 8 days. LHb transfusion suppressed HIF1 expression in the heart, maintained low levels of hFAB, and attenuated sympathetic nerve activity as reflected by changes in HRV and catecholamines. 2) After cannulating 22G catheter into the abdominal aorta, acute HS was induced by withdrawing 30% of total blood for 25 min. After HS, the rats were immediately resuscitated by transfusing the same amount of wRBC, LHb, or 5%ALB. After excising the heart, OMP and EPS were performed in Langendorff-perfused hearts. OMP revealed abnormal ventricular conduction delay in conjunction with impaired action potential duration (APD) dispersion in 5%ALB. In contrast, myocardial conduction velocity and APD dispersion were substantially attenuated in wRBC or LHb. Sustained VT/VF was easily provoked by burst pacing stimulus to the LV in 5%ALB whereas no VT/VF was induced with wRBC or LHb. Conclusions: The results indicate that wRBC and LHb attenuates cardiac dysfunction and sympathetic overactivity during lethal HS. Oxygenated hemoglobin transfusion by using either wRBC or LHb prevents VT/VF by preserving myocardial electrical structures caused by ischemia-reperfusion injury in HS.