tbuckley/cabot-search huggingface dataset:
A phase II trial of capecitabine plus cisplatin (XP) for patients with advanced gastric cancer who relapsed after S-1 adjuvant therapy, XP after TS-1 adjuvant failure (XParTS).
Authors: Masazumi Takahashi, Akira Tsuburaya, Kazuhiro Nishikawa, Kazuaki Tanabe, Kensei Yamaguchi, Shigefumi Yoshino, Tsutomu Namikawa, Takaki Yoshikawa, Yasushi Rino, Junji Kawada, Akihito Tsuji, Koichi Taira, Ryohei Kawabata, Yasuhiro Kodera, Yoshinori Hirashima, Hiroshi Yabusaki, Naoki Hirabayashi, Kazumasa Fujitani, Satoshi Morita, Junichi Sakamoto
Journal: Journal of Clinical Oncology (2015)

124 Background: For gastric cancer, standard regimens including S-1 for adjuvant and first-line chemotherapy have been established in Japan, while for early relapse after adjuvant therapy there is no standard treatment. In our retrospective analysis, relapse-free interval of less than 6 months was associated with poor progression-free survival (PFS) and overall survival (OS). To evaluate the efficacy and safety of capecitabine plus cisplatin (XP) treatment, for patients with advanced gastric cancer who relapsed within 6 months after S-1 adjuvant therapy, we conducted a multicenter phase II trial in Japan (NCT Identifier: NCT01412294). Methods: Patients who had received adjuvant chemotherapy for gastric cancer including S-1 for more than 12 weeks, thereafter relapsed within 6 months, 20–74 years of age and HER2- negative, were assigned to receive capecitabine 1000 mg/m2 bid for 14 days plus cisplatin 80 mg/m2 (day 1) every 3-week. The primary endpoint was PFS and the secondary endpoints were OS, time to treatment failure, overall response rate (ORR) and safety. Planned sample size was 40 according to median PFS threshold of 2 months. Results: From June 2011 to April 2014, 40 patients were assigned. Median age was 64, 32 males (80%); adjuvant chemotherapy: regimen, S-1 monotherapy (n=34, 85%), and median number of course was 7.0 (3-18). In 40 patients median PFS was 20 weeks (95%CI, 17-24), which was longer than protocol-specified threshold of 2 months. Median OS was 77 weeks (95%CI, 34-NE), ORR was 8/40 (22% including 12 NE cases; 95%CI, 44-74). Most common grade ≥3 adverse events (AEs) were neutropenia (23%), anemia (18%), hypercreatinine (18%), fatigue (13%), diarrhea (7.5%), and anorexia (7.5%). Conclusions: XP was safe and effective for those patients with relatively poor prognosis after S-1 adjuvant failure. Since profile of S-1 and capecitabine was different, XP can be recommended rather than S-1 plus cisplatin, Japanese standard first- line regimen. Clinical trial information: NCT01412294.
Chemotherapy error: Analysis of an error reporting database, recent case reports, error reduction methods, current reporting systems
Authors: T. J. Harris, D. W. Northfelt
Journal: Journal of Clinical Oncology (2005)

6091 Background: Medical error, including cancer chemotherapy error (CE), is a significant national concern. CE is among the most serious type of medical error due to high potential of chemotherapy for toxicity and narrow therapeutic index. Chemotherapy is given to patients physiologically compromised by underlying disease, further amplifying risk for harm. Therefore, CE is an important issue for evaluation and remedial action. Methods: Current status of CE was evaluated through: 1) query and analysis of U.S. Pharmacopeia (USP) database of medication errors and 2) literature review to identify recent case reports of CE. Remedial actions to reduce CE were evaluated by identifying error reduction strategies and CE reporting methodologies via web and literature search. Telephone and e-mail queries were also utilized. Results: There were 296 episodes of CE involving 30 common chemotherapeutic agents found in the USP database from 1998–2002. A contemporaneous literature review was also performed. Table 1 provides the details of both. A compilation of error reduction strategies identified was compiled. Our search identified no comprehensive systems for detection, reporting, evaluation or system refinement related to CE. Conclusions: Analysis of CE reporting suggests avenues for remedial action. A universal system for CE reporting with simple reporting format, non-punitive review, and expert feedback could encourage more comprehensive reporting of CE. This would lead to more robust understanding, in turn promoting changes in policies/procedures, ultimately reducing CE and improving patient safety. No significant financial relationships to disclose.
WITHDRAWN: Supplemental therapy of tumor suppressor microRNA using folate-PEG-appended dendrimer (G4) conjugate with α-cyclodextrin
Authors: Yuki Otosu, Ayumu Ohyama, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer.
Authors: F V Fossella, J S Lee, W K Murphy, S M Lippman, M Calayag, A Pang, M Chasen, D M Shin, B Glisson, S Benner
Journal: Journal of Clinical Oncology (1994)

PURPOSE We conducted a phase II study to determine the response and toxicity of docetaxel (Taxotere; Rhône-Poulenc Rorer Pharmaceuticals, Inc, Collegeville, PA) in chemotherapy-naive patients with advanced non-small-cell lung cancer. PATIENTS AND METHODS We treated 41 chemotherapy-naive patients who had stage IIIb or IV non-small-cell lung cancer with 100 mg/m2 of docetaxel intravenously over 1 hour every 3 weeks. Responses were assessed after every one to two treatment courses. Responses of 39 of 41 patients were assessable. The patient's median age was 63 years; 90% of patients had a Zubrod performance status of 0 or 1. The predominant histology was adenocarcinoma (54%), and 90% of patients had stage IV disease. RESULTS Thirteen patients (33%) achieved a partial response to treatment, and the median response duration was 14 weeks. Grade 3 or 4 neutropenia occurred in 97% of patient; this was usually of brief duration and was associated with serious infection in 17% of patients. Other acute toxic effects included easily treated hypersensitivity reactions (36% of patients) and dermatitis (74%). We also observed fluid retention (with peripheral edema or pleural effusion or both) in 54% of patients. This was a cumulative side effect that generally occurred late in treatment. CONCLUSION Docetaxel administered at 100 mg/m2 intravenously every 3 weeks has significant activity against non-small-cell lung cancer, with a 33% major response rate. Primary toxicities were neutropenia, hypersensitivity, and fluid retention.
Impact Of Liver Iron Overload On Myocardial T2* Response In Transfusion-Dependent Thalassemia Major Patients Treated With Deferasirox For Up To 3 Years
Authors: John Porter, Ali T Taher, Yesim Aydinok, Maria D Cappellini, Antonis Kattamis, Ali El-Ali, Nicolas Martin, Dudley Pennell
Journal: Blood (2013)
The Breathing Bus – A primary care model for identifying undiagnosed COPD in hard to reach populations. A pilot study
Authors: June Roberts, Helena Cullen, Nawar Diar Bakerly
Journal: European Respiratory Journal (2011)

Background: COPD is frequently undiagnosed especially in socio-economically deprived (SED) populations who are most at risk of this condition.

Aims: To improve access to hard to reach groups

To identify those most at risk of having undiagnosed COPD and to signpost to general practice for further assessment

Methods: A mobile health bus was sited in areas of high SED with good footfall and accessibility. Nurses trained to recognise COPD syptoms, perform FEV6 micro-spirometry and experienced in informal, non-medicalised approaches to health and disease staffed the bus. High risk individuals (over 35 yrs, smoker or ex-smoker with symptoms suggestive of COPD) were targeted for FEV6 micro-spirometry. Consent was gained to share all results with own GP. Those with unexplained respiratory symptoms and/or abnormal FEV6 readings were asked to see their GP for further assessment. Follow up with patient experience survey took place 8 weeks after a visit to the bus.

Results: The bus visited 6 sites on 7 occasions. 350 people visited the bus, between 6% and 87% of contacts were from areas of high SED. Of 119 in the high risk group, 67% men and 45% females had symptoms suggesting COPD and of those suitable for FEV6 readings 30% of men and 38% women had airflow obstruction: all were signposted to their GP. 48% were current smokers. Data from the experience survey indicates that many suspected something was wrong; accessibility and convenience prompted them to come forward for testing.

Conclusion: Our pilot work suggests that mobile units in non-clinical settings can increase accessibility to SED groups and prompt high risk individuals to be tested for COPD. Further work is needed.
Setting International Standards for the Management of Public Health Pesticides
Authors: Henk van den Berg, Rajpal Singh Yadav, Morteza Zaim
Journal: PLoS Medicine (2015)

Recent developments have highlighted the urgency of sound management of public health pesticides in vector-borne–disease–endemic countries. Major shortcomings are evident in national-level management practices throughout the pesticide life cycle from production to disposal; these shortcomings will adversely affect the cost-effectiveness and increase the risks of pesticides used. A major thrust has occurred towards developing international standards for improvement of public health pesticide management and towards expanding WHO’s global network on pesticide evaluation. However, to face current and future challenges, such as insecticide resistance in malaria vectors, the global capacity for evaluation of new insecticide products and vector-control tools should be further enhanced. Another area requiring urgent attention is the actual adoption and implementation of the recommended standards, calling for support to strengthen policy, legislation, and capacity.
Endobronchial ultrasound transbronchial needle aspiration at Aberdeen Royal Infirmary: How are we doing?
Authors: David Miller, Pratheega Mahendra, Valerie Bruce, Keith Kerr, Mary McKean, Mahendran Chetty, Graeme Currie
Journal: European Respiratory Journal (2012)

Background: Endobronchial ultrasound transbronchial needle aspiration(EBUS-TBNA) is a more convenient alternative to mediastinoscopy for sampling mediastinal lymph nodes. We describe the demographics, results and diagnostic sensitivity of EBUS-TBNA in the 1st 100 procedures performed.

Methods: Since the service began in 2010, patient age, gender, length of procedure, sedative doses, numbers of passes for each node and results were recorded and retrospectively analysed.

Results: Of 100 patients, 66 were male with mean age 62 years (range 22-88). Mean procedure duration was 16 minutes, and median doses of midazolam and fentanyl were 4mg and 100mcg respectively. 142 lymph nodes were sampled with median number of passes of 4 per node.

Lymphoid material was obtained from 126 (86%) of all nodes sampled. A pathological abnormality was found in 73 patients: NSCLC (n=34), SCLC (n=20), granulomatous inflammation (n=14), possible lymphoma (n=1) and metastatic neck (n=1), urological (n=2) and breast cancer (n=1). In the remaining 27 patients, no lymph node was sampled in 10 and lymph node was sampled in 17 cases with no abnormality noted; of the latter, 9 were true negatives. The diagnostic sensitivity for all 100 cases was 81% (77% in the first 50 procedures versus 84% in the remainder).

Conclusions: A variety of cell types can be identified using EBUS-TBNA. Our overall diagnostic sensitivity was 81% with the top of the learning curve almost reached after 50 procedures. The high diagnostic sensitivity implies that many mediastinoscopies can be avoided with potential financial savings.
Cognitive behavioural therapy shows promise in heart failure patients with depression
Authors: Jacqui Wise
Journal: BMJ (2015)

Cognitive behavioural therapy for heart failure patients with depression can considerably improve their emotional health and overall quality of life, a US study published in JAMA Internal Medicine has shown. However, the intervention did not improve heart failure self care or physical functioning when compared with enhanced usual care.1

Major depression is a common comorbidity in heart failure. Depression and inadequate self care are common and inter-related problems that increase the risk of hospitalisation and death in patients …
"Prophylactic" lymph node dissection in melanoma: does it help?
Authors: B Cady
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.1.2 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3275749 "Prophylactic" lymph node dissection in melanoma: does it help? B CadyxB CadySearch for articles by this author https://doi.org/10.1200/JCO.1988.6.1.2 First Page PDF © 1988 by American Society of Clinical Oncology
Pilot trial of a synthetic breakpoint peptide vaccine in patients with chronic myeloid leukemia (CML) and minimal disease
Authors: P. G. Maslak, T. Dao, S. Gupta, M. Gomez, S. Chanel, T. Korontsvit, V. Zakhaleva, S. Ashraf, E. Berman, D. Scheinberg
Journal: Journal of Clinical Oncology (2006)

6514 Background: CML is characterized by a tumor-specific fusion oncoprotein, BCR-ABL. Peptides spanning the B3A2 breakpoint of BCR-ABL can elicit MHC restricted T cell responses and clinical responses. No such data have previously been reported for vaccines targeting B2A2. Methods: We initiated a clinical trial administering synthetic analog breakpoint specific peptide vaccines for either B3A2 or B2A2 breakpoints to CML patients with major or complete cytogenetic remission. Measurable minimal disease was determined by either quantitative polymerase chain reaction (RQ-PCR) or nested PCR for BCR-ABL. Vaccine was administered with GM-CSF and Montanide ISA 51 subcutaneously. Eleven vaccinations were planned over the course of 1 year with the first 5 doses administered bi-weekly. Results: Eleven of 20 planned patients have been accrued to the study. Eight had documented cytogenetic remission and 3 were BCR-ABL positive via FISH analysis. Seven of the 11 patients had measurable BCR-ABL transcript levels as determined by RQ-PCR and all 11 were positive using the nested technique. Of the 5 patients positive for BCR-ABL (by RQ-PCR) before vaccination, 3 converted from RQ-PCR positive to negative while the transcript levels in the other patients decreased by approximately 1 log after 5 doses. All 5 of these patients remained positive using the nested PCR technique. Vaccination was well tolerated with local skin reactions at the injection sites. Immunologic reactivity was assessed ex vivo by CD4 autologous proliferation assay and T cell interferon (IFN) secretion (ELISPOT) assay. Ten of 11 patients were immunologically unreactive to the peptides prior to the vaccinations. Following the 5th dose of vaccine, 8/8 patients (including 2 with B2A2) tested showed significant immunologic responses by one of the above assays. Conclusions: These preliminary results suggest vaccination with synthetic analog peptides derived from CML proteins results in immunologic responses and may be associated with molecular improvement. Clinical efficacy of these vaccines in reducing/ eliminating minimal disease has yet to be established. [Table: see text]
An in vitro test of the cell stretch-proliferation hypothesis of renal cyst enlargement.
Authors: G A Tanner, P F McQuillan, M R Maxwell, J K Keck, J A McAteer
Journal: Journal of the American Society of Nephrology (1995)

In renal cystic disease, fluid accumulation within cyst lumens might stretch cyst walls and in this way stimulate cell proliferation. To test this idea, the effects of mechanical stretch on Madin-Darby canine kidney cells grown as cysts in a hydrated collagen gel or as monolayers on collagen-coated Flexcell membranes were examined. The percentage of cells synthesizing DNA (labeling index) was determined by measuring bromodeoxyuridine incorporation and counting cell numbers. The distension of single cysts for 1 h by the intraluminal injection of saline failed to produce a significant increase in labeling index. The exposure of cysts for 2.5 h to 1 mM dibutyryl cAMP + 0.1 mM isobutylmethylxanthine led to a 37% increase in luminal surface area (due to stimulated fluid secretion) and a 30% increase in labeling index. The stretch (25%) of Madin-Darby canine kidney monolayers approximately doubled the labeling index between 12 and 24 h after starting the stretch. After 48 h, the cell population density was significantly increased (P < 0.001), from 41.9 +/- 0.2 (SE; N = 12) to 48.2 +/- 0.5 (N = 12) cells/10,000 microns2. The labeling index increased linearly with applied stretch, from 7.2 +/- 0.3% (N = 36) with no stretch to 16.2 +/- 1.0% (N = 6) with 30% stretch. Stretch had to be maintained for 8 h or more to produce an increase in labeling index at 18 h. No evidence was obtained for the release of a diffusible growth factor by stretched monolayers. The increase in labeling index induced by stretch was unaffected by 50 microM gadolinium, a stretch-activated channel blocker, but was abolished by 5 micrograms/mL cytochalasin B, an actin microfilament-disrupting agent. It was concluded that prolonged stretch stimulates renal epithelial cells to synthesize DNA. This supports the idea that increased wall tension in renal cysts may stimulate cell proliferation and, thereby, may contribute to cyst enlargement.
Evaluation of plectin-1 immunohistochemical staining in human non-small cell lung cancer
Authors: T. J. Harris, D. R. Jones, C. M. Brenin, K. A. Kelly, K. George, C. A. Moskaluk
Journal: Journal of Clinical Oncology (2009)

e22118 Background: Plectin-1 (PLEC1), a known scaffolding protein, impacts signaling pathways and has been found to be up-regulated and redistributed to the cell membrane in tumor cells. The redistribution of PLEC1 has shown promise as a novel molecular imaging biomarker in experimental systems. The purpose of this study was to examine the variation of PLEC1 staining in human non-small cell lung cancer (NSCLC). Methods: 142 NSCLC samples from 2001–2003 were obtained from pathology archives and placed into tissue microarray (TMA) format. TMA sections were stained with anti-PLEC1 antibody. A total PLEC1 immunohistochemical (IHC) staining score was obtained by multiplying the intensity of PLEC1 staining, scored 0 through 3, by the percent of tumor cells showing membrane staining, scored 1 for &lt;25%, 2 for 25%-75% and 3 for &gt;75%. The samples were then grouped into low (0–2), intermediate (3–5) or high (6- 9) membrane expression and analyzed for clinical correlations to tumor type and pathological staging. Results: A total of 125 samples were successfully stained for PLEC1. In all NSCLC subgroups, there was variability of PLEC1 staining. Approximately 50% of cases showed intermediate to high staining. There was a trend of lower PLEC1 staining as the tumor stage advanced (p=0.1). There appeared to be no significant variations of PLEC1 staining when compared to gender of the patients. Conclusions: These findings are the first to show that a significant number of human NSCLC exhibit strong expression of PLEC1 in the cell membrane. As this biomarker is being developed for molecular imaging modalities in other tumor types, it may have potential to be of use in the non-invasive detection of disease or therapeutic efficacy monitoring in NSCLC. [Table: see text] No significant financial relationships to disclose.
Phase II study of degarelix/bicalutamide combination for prostate cancer.
Authors: Masahiro Nozawa, Takahide Sugiyama, Koichi Sugimoto, Tasuharu Nagai, Yuji Hatanaka, Takashi Oki, Hideo Tahara, Hisao Matsuda, Hirotsugu Uemura
Journal: Journal of Clinical Oncology (2015)

e16005 Background: Gonadotropin-releasing hormone (GnRH) agonist has been used for androgen-deprivation therapy (ADT) for prostate cancer (PCa). Antiandrogens have been used to prevent symptoms due to testosterone surge caused by an agonistic effect in the early phase of treatment as well as to add antitumor efficacy. Degarelix, an antagonist of GnRH does not introduce testosterone surge, however, the combination of degarelix and antiandrogen can exert a stronger antitumor effect than degarelix alone. We conducted a phase II study to investigate the early-phase efficacy and safety of degarelix/bicalutamide combination compared with degarelix alone in patients with PCa. Methods: Patients with histologically proven adenocarcinoma in the prostate indicated for ADT were randomly assigned to a treatment group with either combination of degarelix and bicalutamide or degarelix alone. Degarelix was administered subcutaneously with an initial dose of 240 mg followed by 80 mg thereafter every four weeks. Bicalutamide was taken 80 mg every day. The primary endpoint was the percentage of patients whose serum prostate-specific antigen (PSA) declined with greater than 90% of the baseline at Day 28. Secondary endpoints were the transition of serum PSA and testosterone during treatment of 12 weeks, safety, and quality of life. Results: A total of 100 patients were evaluable in the current interim analysis. Median age was 75 years. Median baseline serum PSA was 10.2ng/ml. The percentage of patients with serum PSA declines greater than 90% from baseline was 33% and 24% in the combination group and the degarelix monotherapy group, respectively (P= 0.382). The decrease rate of serum PSA during treatment of 12 weeks was greater in the combination group than in the degarelix monotherapy group. The transition of serum testosterone level was similar in the both groups. Conclusions: Degarelix/bicalutamide combination for PCa can produce a greater impact on serum PSA decline from the early treatment phase than degarelix alone. Clinical trial information: UMIN000011506.