tbuckley/cabot-search huggingface dataset:
A phase II trial of capecitabine (X) and irinotecan (I), in a biweekly schedule, for patients (Pts) with advanced/metastatic colorectal cancer (MCRC)
Authors: P. Garcia- Alfonso, C. Gonzalez-Arenas, E. Gonzalez-Flores, M. Molina, A. Muñoz, G. Abad, S. Garcia-Adrian, P. Lopez, J. Belon, G. Perez-Manga
Journal: Journal of Clinical Oncology (2004)

3683 Background: X and I are active in MCRC. The combination of these 2 agents has been shown to be synergistic. We conducted a phase II study of XI combination in a biweekly schedule in previously untreated pts with MCRC to evaluate the objective response rate (ORR), safety profile, time to progression (TTP) and overall survival (OS). Methods: Patients with histologically proven MCRC, measurable disease according to RECIST, ECOG PS ≤2 and adequate bone marrow, renal and hepatic functions were included. No prior chemotherapy (except adjuvant therapy) was allowed. Pts received I 175 mg/m2 iv D1 followed by oral X 1000 mg/m2 twice daily from D2–8. For patients >65 years, I and X were reduced to 140 mg/m2 and 750 mg/m2 twice daily, respectively. Cycles were repeated every 14 days. Toxicity was evaluated every cycle using NCI toxicity criteria. Results: 32 pts were enrolled to date: M/F, 22/10, median age was 68 years (49–80), 18 (56%) of pts were > 65 years, ECOG PS 0–1: 91%. Primary tumor sites were colon 47% (n=15), rectum 50% (n=16) or both 3% (n=1). Median number of metastatic lesions was 2 (19% with ≥2 sites) in liver (66%), lung (34%), lymph nodes (13%) and local recurrence (9%). To date, 280 cycles (median 10.5, range 2–12; ≤65/>65 142/138) were administered. Median relative dose intensity was 86% for X and 99% for I (89 and 99%, respectively, for pts >65years). All patients were evaluated for toxicity (see table) and 20 pts for response to date: 2 achieved CR, 8 PR, 3 SD and 7 PD resulting in an ORR of 50% (CI 95%: 27–73) and tumor growth control (RR + SD) in 65% of patients (CI 95%: 41–85). Median TTP and OS were not achieved yet. Conclusions: Capecitabine and Irinotecan, in a biweekly schedule, as 1st line treatment of MCRC is an active combination with a manageable toxicity profile, even in patients >65 years. No significant financial relationships to disclose.
HER2 overexpression and amplification in advanced ovarian cancer (OC): Preliminary results from a large GINECO study
Authors: S. Camilleri-Broët, J. P. Guastalla, J. Couturier, H. Curé, F. Penault-Llorca, D. Allouache, A. Vincent-Salomon, D. Paraïso, E. Pujade-Lauraine
Journal: Journal of Clinical Oncology (2005)

5059 Background: The efficacy of trastuzumab (Herceptin; H) in breast cancer is dependent on HER2 protein overexpression and gene amplification. Some studies have shown that HER2 overexpression is related to a worse prognosis in OC. However, data on the benefit of H in OC are limited. The GINECO group has begun a clinical trial, TC-Herceptin1, in order to investigate the efficacy and tolerance of H in combination with paclitaxel (T) and carboplatin (C) in patients (pts) with progressive OC under TC or in early relapse (< 6 months). Methods: 257 pts with advanced OC were screened for HER2 status (194 pts included in a first-line clinical trial [TCG], and 63 pts with OC recurrence after another first line of chemotherapy). Where possible, determination of HER2 status was carried out in groups of four (two primary tumours and two metastases) because of the high heterogeneity of HER2 immunostaining in ovarian cancers. All positive (3+) and doubtful (2+) cases were screened for HER2 amplification by fluorescence in-situ hybridisation (FISH). Results: Of the 257 cases tested, 15 (6%) were HER2+ by immunohistochemistry (IHC) and FISH. Among the positive cases, 12 were IHC 3+ and three were IHC2+. Heterogeneous staining was found in 8/15 positive cases, with perfect concordance between HER2 overexpression and HER2 gene amplification in the same cells. After screening, three patients were enrolled in the TC-Herceptin1 trial. Conclusions: Despite of a low rate of HER 2 overexpression (6%), the combination of H with chemotherapy in resistant OC pts merits further investigation as effective therapeutic options for these pts are limited. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, SAS
Derivation and Biologic Properties of Cell Lines From Ophidian Tissues
Authors: Henry C. Orr, Peter G. Probst, Joseph L. Rogers, Joseph P. Davis, Naomi T. Stocks, James Baker
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Derivation and Biologic Properties of Cell Lines From Ophidian Tissues Get access Henry C. Orr, Henry C. Orr Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter G. Probst, Peter G. Probst Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph L. Rogers, Joseph L. Rogers Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph P. Davis, Joseph P. Davis Search for other works by this author on: Oxford Academic PubMed Google Scholar Naomi T. Stocks, Naomi T. Stocks Search for other works by this author on: Oxford Academic PubMed Google Scholar James Baker James Baker Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 3, September 1973, Pages 827–832, https://doi.org/10.1093/jnci/51.3.827 Published: 01 September 1973 Article history Received: 16 February 1973 Accepted: 03 May 1973 Published: 01 September 1973
NEWER ASPECTS OF SOME NUTRITIONAL DISORDERS
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 9421: Additional Wiping of the Skin With 70% Isopropil Alcohol Just Before Routine Povidone-Iodine Antisepsis Reduces Cardiac Implantable Electronic Device Infections
Authors: Takanori Takahashi, Junichi Shimotakahara, Nobuhito Yagi, Jun Nakazato, Tadayoshi Miyagi, Minoru Wake, Kazuhito Hirata
Journal: Circulation (2014)

Introduction: Cardiovascular Implantable Electronic Device(CIED) Infections are one of the most serious complication after CIED implantation or replacement. To prevent infection, appropriate skin antisepsis and perioperative antibiotic prophylaxis at CIED implantation/replacement are important. But the most optimal antisepsis for CIED surgery is not well defined. Then we assessed whether additional wiping of the skin with 70% isopropyl alcohol just before routine skin antisepsis with povidone-iodine reduces the incidence of CIED infection. Methods: Consecutive 473 cases of CIED implantation or generator replacement from Jan.2008 to Dec.2013 at one community hospital were divided into two groups according to preoperative skin antisepsis with 70% isopropyl alcohol wipes lasting for at least 1 minute just before povidone-iodine scrub and paint(IPA group, n=183), or povidone-iodine only(No IPA group, n=290). All cases received perioperative antibiotic prophylaxis 30 minute before and 6 hours after procedure. Incidence of CIED infection requiring complete extraction of the leads and the generator within 1-year after implantation/replacement were compared between two groups by Kaplan-Meier analysis. Results: There were no significant difference in background CIED infection risk factors identified by past studies (diabetes, renal insufficiency, anticoagulant use, corticosteroid use, tempolary pacing, and generator replacement) between two groups. During the follow up period, 8 cases of confirmed CIED infection requiring complete extraction were identified, 6 pacemaker and 2 implantable cardioverter-defibrillator(ICD) or biventricular ICD. All infected cases belonged to No IPA group (p = 0.0235). Conclusions: In conclusion, wiping of the skin with 70% isopropyl alcohol just before routine antisepsis with povidone-iodine at CIED implantation/replacement significantly reduces the incidence of infection.
Hematologic and cytogenetic (CTG) response to lenalidomide (CC-5013) in patients with transfusion-dependent (TD) myelodysplastic syndrome (MDS) and chromosome 5q31.1 deletion: Results of the multicenter MDS-003 Study
Authors: A. F. List, G. Dewald, J. Bennett, A. Giagounadis, A. Raza, E. Feldman, B. Powell, P. Greenberg, J. Zeldis, R. Knight
Journal: Journal of Clinical Oncology (2005)

5
Combined inhibition of mTORC1 with temsirolimus and HER2 with neratinib: A phase I study in patients with metastatic HER2-amplified breast cancer.
Authors: D. Gajria, T. A. King, H. Pannu, R. Sakr, A. D. Seidman, A. Syldor, S. Patil, M. Maybody, L. Norton, N. Rosen, C. Hudis, S. Chandarlapaty
Journal: Journal of Clinical Oncology (2011)

574 Background: Hyperactivation of the PI3K-AKT-mTOR pathway is a postulated mechanism of resistance to anti-HER2 therapies. In laboratory models, inhibition of this pathway induces activation of upstream receptor tyrosine kinases such as HER3. We hypothesize that dual inhibition of the PI3K pathway and induced HER3 may be highly effective in patients (pts) with HER2-amplifed (HER2+) breast cancers (BC). This phase I trial aims to determine the tolerability and efficacy of the mTOR inhibitor temsirolimus (T) plus the HER1/2 inhibitor neratinib (N) in pts with trastuzumab-refractory, HER2+ BC. We further sought to ascertain if mutational activation of the PI3K pathway is present in trastuzumab-refractory tumors and affects the response to the T-N combination. Methods: This 3+3 dose-escalation study investigated T (flat dose IV weekly) plus N (240 mg oral daily) in pts with HER2+ metastatic BC. Cycle length was 4 weeks. End points included definition of maximum tolerated dose (MTD) and response rate (RR) per RECIST. Response was evaluated radiographically every 8 weeks, toxicity assessed every 2 weeks. All pts underwent biopsy of metastatic disease for biomarker assessment. Activating mutations in PIK3CA were assayed using the Sequenom MassARRAY system. Expression of PTEN was assessed by immunohistochemistry utilizing a published scoring system. Results: Eight pts enrolled and received a median of 4 (1-8) cycles of therapy. All pts had received trastuzumab and a median of 5 (2-12) prior lines of therapy. Frequent treatment-related grade 2 events were: hyperglycemia (4/8), elevated CPK (3/8), diarrhea (2/8), and rash (2/8). Grade 3 diarrhea was the dose-limiting toxicity; other grade 3 toxicities and hematologic toxicities were not observed. The MTD of temsirolimus with neratinib is 8 mg IV weekly. Six pts treated at MTD were evaluable for response; 4 pts had PR, 1 had SD for a RR of 67%. Molecular analyses revealed PI3K pathway activation in 4/6 tumors analyzed. Conclusions: Temsirolimus plus neratinib has clinical activity and was well tolerated in pts with trastuzumab-refractory HER2+ BC. Additional efficacy and safety data, and final tumor analyses will be presented.
Rheumatic diseases should be actively treated in pregnancy, new guidelines say
Authors: Jacqui Wise
Journal: BMJ (2016)

New guidelines on prescribing anti-rheumatic drugs for pregnant and breastfeeding women, published in the Rheumatology journal, warn against withdrawing potentially beneficial treatment and recommend the best treatment approaches.

Prescription of many anti-rheumatic drugs in pregnancy is complicated by safety concerns, and this has sometimes led to the withdrawal of potentially beneficial treatment. But the new guidelines, produced by the British Society for Rheumatology and British Health Professionals in Rheumatology,1 2 say …
Phase II trial of concomitant low dose temozolomide with external beam radiation (EBRT) followed by 12 months of temozolomide and irinotecan for newly diagnosed glioblastoma (GBM): Preliminary results of RTOG 04–20
Authors: F. S. Lieberman, C. Tsien, B. Berkey, W. Curran, M. Werner-Wasik, R. Smith, L. Grossheim, E. Hug, M. Mehta
Journal: Journal of Clinical Oncology (2006)

1510 Background: Irinotecan and temozolomide compare favorably to regimens tested in recurrent GBM. RTOG 04–20 intensifies the Stupp R, et al. (N Engl J Med. 2005 Mar 10;352(10):987–96) adjuvant regimen, using irinotecan and temozolomide in place of temozolomide alone. Methods: Adult patients with newly diagnosed histologically confirmed, supratentorial GBM were eligible. Subjects began temozolomide 75mg/m 2 daily the night before initiation of EBRT, and continued until the final day of RT. Pneumocystis prophylaxis was begun prior to RT and for 2 weeks following RT. Within 6 wks after EBRT, subjects with stable or improved MRI were scheduled to receive temozolomide 150mg/m 2 on days 1–5, and irinotecan 200mg/m 2 on days 1 and 15 of 28 day cycles × 12. Clinical assessments and post contrast MRI are required prior to EBRT, after RT, and after every 2 treatment cycles. Only nonenzyme inducing anticonvulsants were allowed. Results: Accrual of 170 patients was completed in September 2005 with 140 patients currently evaluable. Median age is 57yr, 80% were RPA class III or IV. Prior to cycle 1 of adjuvant therapy, 32 subjects withdrew (20 progressed, 4 toxicity). Of the first 25 subjects receiving irinotecan, 10 suffered grade 3–4 hematologic toxicities in the initial 3 cycles. The protocol was modified by dose reducing irinotecan to 100mg/m 2 in cycle 1, escalating to 150 and 200mg/2 in subsequent cycles only if no dose limiting hematologic toxicity occured. No data is yet available on patients who started adjuvant therapy at the lower dose of irinotecan. Diarrhea and constitutional symptoms are the most common nonhematologic toxicies Conclusions: Irinotecan 200mg/m 2 days 1 and 15 with temozolomide 150mg/m 2 days 1–5 of 28 day cycles was well tolerated treating recurrent GBM, but this regimen was too myelosuppressive when given after concomitant low dose temozolomide and EBRT. Primary outcome data should be available in late 2006. [Table: see text]
Breast cancer molecular subtypes and locoregional recurrence
Authors: M. C. Cheang, D. Voduc, S. Tyldesley, K. A. Gelmon, M. J. Ellis, P. S. Bernard, C. M. Perou, T. O. Nielsen, H. F. Kennecke
Journal: Journal of Clinical Oncology (2008)

510 Background: Gene expression profiling studies have consistently revealed prognostically significant breast cancer subtypes: Luminal A (LumA), Luminal B (LumB), HER2, and Basal-like. This study compares the local and regional recurrence rates within these subtypes. Methods: Tissue microarrays were constructed using 4,046 invasive breast cancers referred to the British Columbia Cancer Agency from 1986 to 1992. Breast cancer subtypes were defined using an immunopanel of ER, progesterone receptor (PR), HER2, epidermal growth factor receptor (EGFR), cytokeratin 5/6 and Ki67. Univariate local and regional relapse risks were estimated using Kaplan-Meier survival curves. For multivariate analysis, stratified Cox models were built to determine the hazard ratios of breast cancer subtypes, adjusting for tumor size, grade, lymphovascular invasion, margin status, nodal involvement and age as covariates, and, for local treatments (lumpectomy + radiation, mastectomy, mastectomy + radiation) as strata. Results: 3,038 breast tumors are classifiable into molecular subtypes. 1,324 (44%) patients had lumpectomy + radiation, 494 (16%) had mastectomy + radiation and 1,220 (40%) had mastectomy alone. Defining ER/PR positive, HER2 negative and Ki67<10% as LumA identifies a low risk subtype. HER2+ (ER/PR negative and HER2 positive), and basal-like (ER/PR/HER2 negative but either EGFR or ck5/6 positive) are associated with increased local and regional relapses confirming the aggressive nature of these two subtypes. Lum/HER2+ (ER/PR positive and HER2 positive) and LumB (ER/PR positive, HER2 negative, Ki67≥10%) subtypes shows significantly worse prognosis in regional but not in local relapse when compared to LumA. Conclusions: Breast cancer subtyping provides additional prognostic information and identifies subgroups with distinct local and regional recurrence risks. Newer targeted systemic treatments may modify this. Breast cancer subtypes association with local and regional relapses HER2+ (N = 252) Basal-like (N = 318) Lum/HER2+ (N = 216) LumB (N = 1109) LumA (N = 1143) Risk of 10-year Local Relapse (%) 18 15 15 11 7 Hazard Ratio, p 1.8, 0.01 1.6, 0.04 1.6, 0.06 1.3, 0.18 1 Risk of 10-year RegionalRelapse (%) 12 15 16 9 3 Hazard Ratio, p 2.9, 0.0003 4.0, 2.1e-07 2.4, 0.004 2.1, 9.1e-04 1 No significant financial relationships to disclose.
Symptom Prevalence and Functional Status Among Patients with Advanced Cancers of the Head and Neck
Authors: T. Shinozaki, M. Ebihara, S. Iwase, T. Yamaguchi, H. Hirakawa, W. Shimbashi, T. Kamijo, M. Okamoto, T. Beppu, J. Ohori, K. Matsuura, M. Suzuki, H. Nishino, Y. Sato, K. Ariyoshi, M. Matoba
Journal: Annals of Oncology (2014)
Are neurological abnormalities in well discordant monozygotic co-twins of schizophrenic subjects the result of perinatal trauma?
Authors: E Cantor-Graae, T F McNeil, K C Rickler, K Sjöström, R Rawlings, E S Higgins, T M Hyde
Journal: American Journal of Psychiatry (1994)

Neurological abnormalities found in schizophrenic subjects and their healthy relatives have raised questions concerning etiology. The aim of the present study was to investigate the genetic and environmental antecedents of neurological impairment in monozygotic twins discordant for schizophrenia, with particular focus on the well discordant twins. The etiological factors of interest were history of obstetric complications, family history of psychosis, history of substance abuse, and history of postnatal cerebral trauma.History of obstetric complications, including information from pregnancy through the neonatal period, and data on neurological "hard" and "soft" signs were obtained blindly and separately for each member of 22 monozygotic twin pairs discordant for schizophrenia and seven normal comparison monozygotic twin pairs. Clinical and family interviews provided information about background factors.Degree of neurological impairment in the well discordant monozygotic twins was significantly positively related to history of both neonatal and total obstetric complications. None of the three other background factors investigated was related to degree of neurological impairment in the ill or well co-twins.The contribution of obstetric complications to the current level of neurological impairment in well discordant co-twins suggests that the spectrum of neuroabnormality, ranging from neurological signs to schizophrenia, in monozygotic discordant twins may be the result of subtle gene-environment interaction.
Updated survival from a randomized phase III trial (MPACT) of <i>nab</i>-paclitaxel plus gemcitabine versus gemcitabine alone for patients (pts) with metastatic adenocarcinoma of the pancreas.
Authors: David Goldstein, Robert Hassan El Maraghi, Pascal Hammel, Volker Heinemann, Volker Kunzmann, Javier Sastre, Werner Scheithauer, Salvatore Siena, Josep Tabernero, Luis Teixeira, Giampaolo Tortora, Jean-Luc Van Laethem, Rosemary Young, Xinyu Wei, Brian Lu, Alfredo Romano, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2014)

178^ Background: In the phase III MPACT trial, nab-paclitaxel (nab-P) + gemcitabine (G) was tolerable and demonstrated superiority to G alone for all efficacy endpoints in pts with metastatic pancreatic cancer (MPC). nab-P + G vs G alone met the study’s primary endpoint by demonstrating a significant improvement in overall survival (OS; median 8.5 vs 6.7 months; HR 0.72; 95% CI, 0.617 - 0.835; P &lt; 0.001) and the secondary endpoints of progression-free survival (PFS; median 5.5 vs 3.7 months; HR 0.69; 95% CI, 0.581 - 0.821; P &lt; 0.001) and overall response rate (ORR; 23% vs 7%; P &lt; 0.001). The 1-year survival rates for nab-P + G vs G alone were 35% vs 22%. The OS data reported above were based on a database cutoff of September 17, 2012, at which time 80% of pts had died. Here, we report an updated OS analysis (post hoc) from MPACT. Methods: 861 pts with MPC and a Karnofsky performance status (KPS) ≥ 70 were randomized at 151 community and academic centers 1:1 to receive nab-P 125 mg/m 2 + G 1000 mg/m 2 on days 1, 8, and 15 of a 28-day cycle or G alone 1000 mg/m 2 weekly for 7 weeks followed by 1 week of rest (cycle 1) and then days 1, 8, and 15 of a 28-day cycle (cycle ≥ 2). The data for this survival analysis were collected through April 1, 2013. Results: As of the updated data cutoff, 380/431 (88%) pts in the nab-P + G arm and 394/430 (92%) pts in the G alone arm had died. OS was superior for nab-P + G vs G alone in the intent-to-treat population, and the longer follow-up allowed an estimate of the 3-year survival rates (Table). The treatment effect was consistent across all pt subgroups examined. Conclusions: This updated survival analysis revealed a sustained difference in OS over time between the 2 arms. MPACT is the first phase III study in MPC to report 3-year survival rates. These data confirm and extend the previous report of the primary endpoint and support the superior efficacy of nab-P + G over G alone. These results may encourage efforts to build upon this well tolerated backbone to further extend survival. Clinical trial information: NCT00844649. [Table: see text]