tbuckley/cabot-search huggingface dataset:
Phase I pharmacokinetic(PK)/food effect and safety study of satraplatin in patients (pts) with advanced solid tumors
Authors: B. J. George, A. D. Ricart, E. Calvo, Q. Chu, J. Sarantopoulos, D. Greene, F. E. Nathan, M. E. Petrone, A. W. Tolcher, K. P. Papadopoulos
Journal: Journal of Clinical Oncology (2006)

12014 Background: Satraplatin (S) is a novel oral platinum analog that has demonstrated preliminary activity in hormone refractory prostate cancer (HRPC). A large (950 pts) worldwide, randomized phase III trial evaluating S as 2 nd line therapy for HRPC recently completed enrollment. The current study was designed to determine the PKs of S under fasted and fed conditions, as well as treatment efficacy and toxicity. Methods: S was administered orally at 80 mg/m 2 /day (d) on d1–5 q 35 days, with prophylactic antiemetics. For the 1st cycle, pts were randomized to receive d1 and d5 doses of S in either the fed or fasted state when PK sampling was performed. The fed/fasted state was reversed for the 2 nd cycle. Subsequent doses of S were given in the fasted state. Results: 17 pts were enrolled (9M/8F), median age 62 (range 33–78) and tumor types: HRPC (7), breast (3), 1 each with anal, parotid, leiomyosarcoma, Merkel cell, ovarian, mesothelioma, and neuroendocrine tumor. The median no. of prior regimens was 3 (range 1–8). A total of 58 cycles of S were given. Grade 3–4 hematologic toxicities (1st 2 cycles) included: neutropenia (11%), thrombocytopenia (24%) and anemia (24%). The hematologic nadir occurred during week 4. There was no grade 3–4 nausea, vomiting or diarrhea. No significant cardiac, renal, hepatic, or neurologic toxicity was observed. The peak plasma concentration (C max ) for platinum in plasma ultrafiltrate (PUF) was decreased by 20% when S was administered following a high fat meal compared to the fasting condition. There was no effect of food on AUC 0–24 hr . The time of C max (T max ) was delayed in the fed state. Table shows PK parameters. One PR (HRPC) and 4 SD ≥ 5 months (breast, ovarian, parotid and HRPC) were confirmed. Conclusions: There is an effect of food on the C max , however the clinical implications are unknown at this time. For this reason, it is recommended that S be administered to pts in the fasting state. At the dose of 80 mg/m 2 /day, S was well tolerated in this group of heavily pretreated patients. [Table: see text] [Table: see text]
Capecitabine after anthracycline and taxane exposure in HER2-negative metastatic breast cancer patients: Response, survival, and prognostic factors.
Authors: M. Gilabert, B. Esterni, F. Bertucci, P. Viens, A. Goncalves
Journal: Journal of Clinical Oncology (2010)

2593 Background: Capecitabine (CAPE) as monotherapy is a widely accepted option in metastatic breast cancer (MBC) patients. However, little is known about specific activity in defined patients, including HER2- and HR- (triple-negative, TPN) MBC patients. Here, we examined response, survival data, and prognostic factors in a prospectively cohort of HER2-MBC pts receiving CAPE after anthracycline and taxane failure in a routine setting. Methods: 75 HER2-MBC patients treated with CAPE between 2002 and 2008 were reviewed. These patients had been pretreated with anthracycline and/or taxane either in adjuvant or metastatic setting. Univariate and multivariate analysis were employed to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). Results: Pt characteristics were the following: median age 53, grade 3 (54%); TPN 21%, <3 metastatic sites before CAPE (78% visceral metastasis (64%). Overall objective response status was : 3 CR (4%), 19 PR (22%), 21 SD (28%), 31 PD (42%). The objective response rates in HER2- HR+ and TPN were 37% and 0%, respectively (p<0.01). After a median follow-up of 35.2 months, median PFS was 6.6 months (95%CI, 4.7-10.4) and median OS was 18.4 months ( 95%CI, 14.1-24.9), respectively. In TPN specially, median PFS and OS were 3.6 and 10.8 months respectively. By multivariate analysis, disease-free interval < 24 months (p=0.0104),TPN (p= 0.0172), and distant lymph node metastasis (p=0.0445) were independent parameters negatively associated with PFS, whereas DFI< 24 months (p=0.0003), time between first metastatic relapse and CAPE treatment < 24 months (p=0.0029), number of metastatic sites (=0.0031), CNS localization (p=0.0050), and grade 2-3 (p=0.0408 and p=0.0057, respectively), were independent parameters negatively associated with OS. Conclusions: Median OS in anthracycline and taxane-pretreated HER2- MBC pts receiving CAPE is nearly 18 months. While CAPE retains significant activity in HER2-HR+ pts, no response and poor outcome were observed in TPN patients. These data suggest that capecitabine is not the most appropriate option in this subgroup. No significant financial relationships to disclose.
Osteonecrosis of the jaw (ONJ) in androgen-independent prostate cancer (AIPC) patients receiving ATTP (bevacizumab, docetaxel, thalidomide, and prednisone)
Authors: J. B. Aragon-Ching, Y. M. Ning, L. Latham, J. Guadagnini, P. M. Arlen, J. L. Gulley, J. Wright, H. Parnes, W. D. Figg, W. L. Dahut
Journal: Journal of Clinical Oncology (2007)

19594 Background: ONJ has been associated with IV bisphosphonate use in cancer patients (pts) and chemotherapy may be an additional risk factor. ONJ is believed to result from localized vascular insufficiency due to faulty bone remodeling. ONJ incidence in pts not receiving chemotherapy (e.g. Paget's disease) is reportedly only 0.8%; prostate cancer pts have an incidence of 6.5%. Methods: We reviewed data from pts with advanced AIPC who developed ONJ while being treated on a Phase II study of ATTP. Results: Six of 36 (17%) pts treated with ATTP had ONJ confirmed by oral surgery. Four of the 6 pts presented with pain and, in five, the ONJ was mandibular in location. All pts were treated conservatively with either sequestrectomy or oral cleansing with chlorhexidine. All pts had been treated monthly with IV zoledronic acid (ZA). The mean duration of ZA use before diagnosis of ONJ was 20 months (mos). One patient had been treated with oral alendronate for 3 years and then developed ONJ after 5 mos of ZA. Of the 36 pts on-study, previous dental history could be verified in 24 pts. ONJ was diagnosed in 4 of the 5 pts with a prior dental infection or invasive dental procedure. Pts received an average of 11 cycles of ATTP before ONJ was diagnosed. All pts with ONJ had received full doses of bevacizumab and most had received full doses of all medications for all cycles. Conclusions: The possibility exists that the risk for ONJ may be higher with specific chemotherapy regimens, particularly those that include steroids or anti-angiogenic agents. However, at this time prior dental infections or procedures remain the greatest known risk factor. It is also possible that the relatively high incidence of ONJ in prostate cancer patients may reflect increased awareness in this population. Randomized phase III trials in AIPC, specifically addressing the incidence of ONJ, are needed to determine whether specific chemotherapy regimens are associated with an increased risk of this complication. No significant financial relationships to disclose.
Antibiotic Use and Mortality Among Premature Infants Without Confirmed Infection—Perpetrator or Innocent Bystander?
Authors: Sagori Mukhopadhyay, Karen M. Puopolo
Journal: JAMA Pediatrics (2016)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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 Pediatrics journal
Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Refractory or Relapsed Non-Hodgkin’s Lymphoma (NHL).
Authors: Hugues de Lavallade, Reda Bouabdallah, Catherine Faucher, Sabine Furst, Jean El-Cheikh, Norbert Vey, Anne-Marie Stoppa, Danielle Sainty, Christine Arnoulet, Luc Xerri, Philippe Cassier, Jean-Albert Gastaut, Didier Blaise, Mohamad Mohty
Journal: Blood (2006)
Extent of resection for curable colorectal cancer in young patients: A 27-year experience at a tertiary care centre
Authors: E. Al-sukhni, P. F. Ridgway, B. O’Connor, R. S. McLeod, C. J. Swallow
Journal: Journal of Clinical Oncology (2009)

e15059 Background: Patients diagnosed with colorectal cancer (CRC) under the age of 50 have an increased lifetime risk of developing metachronous primary tumours. Some familial GI cancer experts have recommended that younger patients with curable CRC undergo definitive subtotal colectomy at initial presentation. We sought to determine the compliance with these recommendations at our institution, the factors predictive of subtotal/total colectomy, and the influence of resection extent on survival. Methods: A case- control study utilised a prospective CRC database at Mount Sinai Hospital, Toronto. All patients under 50 who underwent initial resection of CRC with curative intent from 1979–2007 were included. Patients 50 or over were identified as controls. Type of resection was classified as complete (total/subtotal colectomy, proctocolectomy) or segmental. Results: From the database of over 1400 CRC cases, 201 patients were under age 50. 1182 controls were identified. The young patients had significantly higher rates of identifiable risk factors for CRC (IBD, FAP/HNPCC, family history of cancer) and were significantly more likely to undergo complete resection (23.38% vs 6.01%, OR 4.78). Interestingly, rectum was the primary site in 54.73% of young patients. Factors contributing to complete resection were site of disease (colon), IBD, and family history of CRC (Table). Four patients (2.6%) who underwent segmental resection developed metachronous disease at a median of 66.38 months post resection. No significant change in practice was noted over time. Conclusions: The majority of young patients with curable CRC underwent segmental resection only. Factors predictive of a complete resection included IBD, family history of CRC, and colonic primary site. Overall survival was not influenced by extent of resection. The authors support this pragmatic approach while more sophisticated estimates of tumor biology are being developed to guide the decision for more extensive prophylactic resection. [Table: see text] No significant financial relationships to disclose.
Primary Care Interventions to Support Breastfeeding
Authors: Kirsten Bibbins-Domingo, David C. Grossman, Susan J. Curry, Karina W. Davidson, John W. Epling, Francisco A. R. García, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, C. Seth Landefeld, Carol M. Mangione, William R. Phillips, Maureen G. Phipps, Michael P. Pignone
Journal: JAMA (2016)

<h3>Importance</h3> There is convincing evidence that breastfeeding provides substantial health benefits for children. However, nearly half of all US mothers who initially breastfeed stop doing so by 6 months, and there are significant disparities in breastfeeding rates among younger mothers and in disadvantaged communities. <h3>Objective</h3> To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on primary care interventions to promote breastfeeding. <h3>Evidence Review</h3> The USPSTF reviewed the evidence on the effectiveness of interventions to support breastfeeding on breastfeeding initiation, duration, and exclusivity. The USPSTF also briefly reviewed the literature on the effects of these interventions on child and maternal health outcomes. <h3>Findings</h3> The USPSTF found adequate evidence that interventions to support breastfeeding, including professional support, peer support, and formal education, change behavior and that the harms of these interventions are no greater than small. The USPSTF concludes with moderate certainty that interventions to support breastfeeding have a moderate net benefit. <h3>Conclusions and Recommendation</h3> The USPSTF recommends providing interventions during pregnancy and after birth to support breastfeeding. (B recommendation)
Screening for Potential Covariates Influencing the Pharmacokinetics of Intravenous Busulfan: Results From a Large Pediatric Cohort Undergoing Hematopoietic Stem-Cell Transplantation
Authors: Zeinab Daher Abdi, Angelo Paci, Despina Moshous, Jean-Hugues Dalle, Nathalie Bleyzac, Benedicte Neven, Claire Galambrun, Véronique Kemmel, Aurélie Pétain, Sophie Broutin, Laurent Nguyen, Gilles Vassal
Journal: Blood (2010)
Phase III randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy: Southwest Oncology Group Protocol S0200
Authors: D. S. Alberts, P. Y. Liu, S. Wilczynski, M. Clouser, A. Lopez, M. Lange, V. Lanzotti, M. Markman
Journal: Journal of Clinical Oncology (2007)

5551 Background: There is a continuing debate over the role of combination, platinum-based chemotherapy for PS, recurrent ovarian cancer (OC). Although this phase 3 trial was closed prematurely by the SWOG Data Safety and Monitoring Committee (DSMC) due to slow patient accrual, it provided provocative results nonetheless. Methods: Patients with recurrent stage III or IV OC, with a progression-free and platinum-free interval of 6- 24 months after completion of first-line platinum-based chemotherapy, and up to 12 courses of non-platinum containing chemotherapy or biologic therapy as consolidation treatment after the first-line regimen were eligible and observed for progression-free survival (PFS) and overall survival (OS). Patients were randomized to either IV PLD (30 mg/m 2 ) plus IV carboplatin (AUC=5 mg/mL × min) once every 4 weeks (PLD arm) or IV carboplatin (AUC=5mg/ML × min) once every four weeks alone. Results: The PLD arm enrolled 31 patients and the carboplatin alone arm enrolled 30 for a total of 61 patients out of the 900 planned. The response rates were 67% (18/27) for the PLD arm and 32% (9/28) for the carboplatin only arm (Fisher’s exact p=0.02). The estimated median PFS on the PLD arm was 12 months and 8 months on the carboplatin only arm. The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm (p=0.02). 26% of the patients on the PLD arm reported grade 4 toxicities, all hematological in nature. Conclusions: Although this study was closed early, because of slow patient accrual the results for the PLD arm are intriguing for response rates, median progression-free survival and overall survival. These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS, recurrent disease. No significant financial relationships to disclose.
The “Side-Population” of Human Lymphoma Cells Have Increased Chemo-Resistance, Stem-Cell Like Properties and Are Potential Targets for Immunotherapy
Authors: Jessica Ann Shafer, Ann M. Leen, Conrad Russell Cruz, John A Craddock, Helen E. Heslop, Cliona M. Rooney, Malcolm K Brenner, Catherine M. Bollard, Aaron Foster
Journal: Blood (2008)
Talactoferrin alfa is an anti-cancer agent with activity in renal cell cancer (RCC) patients and a novel immunomodulatory mechanism of action
Authors: A. Varadhachary, M. Spadaro, J. Engelmayer, P. Blezinger, T. Valli, K. Petrak, F. Pericle, M. B. Mokyr, G. Forni, T. G. Hayes
Journal: Journal of Clinical Oncology (2006)

14648 Background: Talactoferrin alfa (talactoferrin) is a novel, orally administered immunomodulatory protein with demonstrated anti-cancer activity in preclinical experiments. Methods: Talactoferrin’s safety and efficacy in cancer patients was evaluated in a Phase I/II trial. Patients with metastatic disease who had failed standard therapy were treated with single-agent oral talactoferrin. Tumors were measured by CT scan using RECIST criteria. Talactoferrin’s mechanism of action was evaluated in preclinical experiments in tumor-bearing immunocompetent BALB/c and knockout mice. Cytokine levels were measured by ELISA. Cellular changes were measured by FACS analysis and immunofluorescence. Results: Seven patients with metastatic RCC who had failed previous systemic therapy were treated with oral, single-agent talactoferrin. Talactoferrin was safe and very well tolerated without a single drug-related SAE. All seven patients achieved at least Stable Disease, with one patient showing a deep and sustained partial response (71% shrinkage by RECIST two years after start of therapy). There was an apparent increase in median PFS to 7.3 months, with two patients still progression free after two years. Median OS has not yet been reached. In experiments conducted to define its anti-cancer mechanism, orally administered talactoferrin was found to act at the gut and the Gut Associated Lymphoid Tissue (GALT). Talactoferrin induced the chemotaxis of immune cells to intestinal Peyer’s Patches in mice, initiating an immunostimulatory cascade in the GALT and activating both innate and adaptive immunity. We observed significantly increased numbers of Dendritic Cells, NK-T cells and CD8+ T-lymphocytes in small intestinal Peyer’s patches, a systemic increase in Natural Killer (NK) and Cytotoxic T-lymphocyte (CTL) activity, activation of tumor draining lymph nodes, and cellular infiltration of distant tumors. The critical role of NK-T and CD8+ cells was demonstrated in knockout and depletion experiments. Conclusions: Talactoferrin, a first-in-class molecule with apparent clinical anti-cancer activity in RCC, acts through a novel immunomodulatory mechanism of action. [Table: see text]
GW26-e3898 A Body Shape Index and Body Roundness Index: Two new body indices to identify left atrial enlargement among rural populations in northeast China
Authors: Ye Chang, Xiaofan Guo, Tan Li, Shasha Yu, Zhao Li, Liang Guo, Shiwen Li, Jie Guo, Xu Wang, Hongmei Yang, Guozhe Sun, Jun Yang, Yingxian Sun
Journal: Journal of the American College of Cardiology (2015)
Ifosfamide or trofosfamide for intraocular lymphoma: Long-term results of a prospective study
Authors: E. Thiel, K. Jahnke, J. Bechrakis, T. Wagner, L. Fischer, P. Kiewe, A. Korfel
Journal: Journal of Clinical Oncology (2007)

18524 Background: The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has not yet been defined. In a prospective study, ifosfamide (IFO) or trofosfamide (TRO) have been assessed for treating IOL. Here, long-term results are presented. Patients and Methods: Patients with histologically proven isolated IOL were included. The median age of the patients was 74 years (range 46–83 years); 4 patients had a newly diagnosed disease and 6 a relapse. IFO was administered intravenously at a dose of 1.5 - 2.0 g/m 2 /day for 3 days every three weeks. TRO was given at a dose of 150 or 400 mg/day (continuous or intermittent administration) to 4 patients considered unable to receive intensive intravenous hydration. IFO, TRO and their active 4-hydroxy (4-OH) metabolites were measured in aqueous humor of 9 patients. Results: The median number of IFO courses was 6 (range 2–8), the median duration of TRO therapy was 8.5 months (range 6–18 months). All patients responded. Toxicity &gt; WHO grade 2 was: anemia grade 2 in 2 patients, leukopenia grade 2–3 in 2 patients, nausea/vomiting grade 2 in 2 patients, thrombopenia and cystitis grade 2 in 1 patient each. Thus far, three patients each have developed cerebral and ocular relapse. Median progression-free survival from the study treatment was 9.5 months (range 6 - 24+ months), median overall survival was 15.5 months (range 6–34 months). Both patients retreated with IFO on ocular relapse responded. In 6 of 6 patients, 4-OH metabolites were detected in the aqueous humor immediately after IFO infusion with an aqueous/serum ratio of 0.19–0.54. Three to 16 hours after ingestion of TRO, 4-OH metabolites could be detected in one of 3 patients. Conclusions: Response rate of IOL to IFO or TRO is high with a tolerable toxicity even in elderly patients. However, long-term remissions are infrequent. Combining IFO/TRO with other cytostatics seems reasonable to improve long-term disease control. No significant financial relationships to disclose.
A Neutralizing Antibody (CSL362) Against the Interleukin-3 Receptor α-Chain Augments the Efficacy of a Cytarabine/Daunorubicin Induction-Type Therapy in Preclinical Xenograft Models of Acute Myelogenous Leukemia
Authors: Erwin M Lee, Dean Yee, Samantha J Busfield, Gino Vairo, Richard B. Lock
Journal: Blood (2012)
Effect of Saxagliptin on Renal Outcomes in the SAVOR-TIMI 53 Trial
Authors: Ofri Mosenzon, Gil Leibowitz, Deepak L. Bhatt, Avivit Cahn, Boaz Hirshberg, Cheryl Wei, KyungAh Im, Aliza Rozenberg, Ilan Yanuv, Christina Stahre, Kausik K. Ray, Nayyar Iqbal, Eugene Braunwald, Benjamin M. Scirica, Itamar Raz
Journal: Diabetes Care (2016)

Dipeptidyl peptidase 4 inhibitors may have a protective effect in diabetic nephropathy.We studied renal outcomes of 16,492 patients with type 2 diabetes, randomized to saxagliptin versus placebo and followed for a median of 2.1 years in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial.At baseline, 9,696 (58.8%) subjects had normoalbuminuria (albumin/creatinine ratio [ACR] <30 mg/g), 4,426 (26.8%) had microalbuminuria (ACR 30-300 mg/g), and 1,638 (9.9%) had macroalbuminuria (ACR >300 mg/g). Treatment with saxagliptin was associated with improvement in and/or less deterioration in ACR categories from baseline to end of trial (EOT) (P = 0.021, P < 0.001, and P = 0.049 for individuals with baseline normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively). At 2 years, the difference in mean ACR change between saxagliptin and placebo arms was -19.3 mg/g (P = 0.033) for estimated glomerular filtration rate (eGFR) >50 mL/min/body surface area per 1.73 m2 (BSA), -105 mg/g (P = 0.011) for 50 ≥ eGFR ≥ 30 mL/min/BSA, and -245.2 mg/g (P = 0.086) for eGFR <30 mL/min/BSA. Analyzing ACR as a continuous variable showed reduction in ACR with saxagliptin (1 year, P < 0.0001; 2 years, P = 0.0143; and EOT, P = 0.0158). The change in ACR did not correlate with that in HbA1c (r = 0.041, 0.052, and 0.036; 1 year, 2 years, and EOT, respectively). The change in eGFR was similar in the saxagliptin and placebo groups. Safety renal outcomes, including doubling of serum creatinine, initiation of chronic dialysis, renal transplantation, or serum creatinine >6.0 mg/dL, were similar as well.Treatment with saxagliptin improved ACR, even in the normoalbuminuric range, without affecting eGFR. The beneficial effect of saxagliptin on albuminuria could not be explained by its effect on glycemic control.