tbuckley/cabot-search huggingface dataset:
XELOX (capecitabine plus oxaliplatin), a safe and active first-line regimen for elderly patients with metastatic colorectal cancer (MCRC): Post-hoc analysis of a large phase II study
Authors: C. Twelves, C. Butts, J. Cassidy, T. Conroy, F. De Braud, E. Díaz-Rubio, J. Tabernero, P. Schöffski, A. Figer, E. Van Cutsem
Journal: Journal of Clinical Oncology (2004)

3555 Background: Tumor-activated capecitabine (Xeloda) has superior response rates and equivalent progression-free and overall survival compared with bolus 5-FU/LV in first-line MCRC, with favorable safety and fewer hospitalizations. This safety advantage is confirmed in the adjuvant setting, where improved safety is also seen in older patients. XELOX is safe and active in first-line MCRC and could also be suitable for older patients. Methods: In this post-hoc analysis of mature safety data in older vs younger patients, 96 patients with MCRC received first-line XELOX: oxaliplatin 130mg/m2 i.v. day 1 followed by oral capecitabine 1,000mg/m2 twice daily, evening day 1–morning day 15, every 3 weeks. All patients are evaluable: 64% male; median age 64 years (34–79); 52 younger patients (<65 years), 44 older patients (≥65 years); median KPS 100 (80–100). Primary tumor: 64% colon; 33% rectal; 3% both. Metastases: 54% >1 metastatic site; 77% liver, 38% lymph nodes, 32% lung. Prior adjuvant fluoropyrimidines: 28%. Results: Patients received a median nine cycles of XELOX. Safety profiles are similar in younger and older patients (table). The incidence of dose reductions and withdrawals for adverse events was similar. The activity of XELOX was also similar in both groups, response rates: 58% (95% CI, 43–71; younger) vs 52% (95% CI, 37–68; older). Conclusions: XELOX has a favorable safety profile with no clinically relevant differences between younger and older patients. Antitumor activity is preserved in older vs younger patients. These results imply that up-front dose reductions are not required when XELOX is prescribed in older patients. Ongoing phase II/III trials are prospectively evaluating XELOX in this population. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche; Sanofi Roche Roche
Meta-analysis comparing carboplatin and cisplatin-based chemotherapy in advanced non-small cell lung cancer
Authors: A. M. Chan, A. J. Mao, T. Wu, Y. Zhang
Journal: Journal of Clinical Oncology (2005)

7218 Background: It is recommended that first-line chemotherapy given to patients with metastatic non-small cell lung cancer (NSCLC) consist of a 2 drug platinum-based combination. The primary objective of this meta-analysis is to compare the efficacy of carboplatin-based and cisplatin-based chemotherapy in terms of median survival in patients with advanced NSCLC. Methods: A literature search was performed using MEDLINE. We selected phase III trials which compared carboplatin-containing and cisplatin-containing regimens in advanced NSCLC. Outcomes recorded were: median survival, 1-year survival rate, and overall response rate. The primary effect measure was difference in median survival between the carboplatin and cisplatin regimens in months. Statistical analysis was performed using Stata version 7.0. Fixed-effects and random-effects models were used to calculate the pooled estimates of difference in median survival, relative risk (RR) of 1-year survival, and RR of overall response. Results were summarised on forest plots. Heterogeneity was assessed using the Q-test and Gallbraith plots. Results: 10 studies were selected for primary analysis, providing 14 carboplatin vs. cisplatin comparisons from 1990 to 2003. There were 3171 patients in carboplatin regimens and 3168 patients in cisplatin regimens. The pooled estimate for difference in median survival is -0.36 months with 95% confidence intervals (CI) of -0.91 to 0.19. The pooled estimate for 1-year survival RR is 0.99, 95% CI 0.94 to 1.05. The pooled estimate for overall response RR is 0.91, 95% CI 0.86 to 0.97. In the subgroup analysis of carboplatin vs. cisplatin comparisons in which the non-platinum drug is the same, the pooled estimate for difference in median survival is -1.03 months with 95% CI -2.13 to 0.09. Conclusions: Carboplatin-based and cisplatin-based chemotherapy are equivalent in advanced NSCLC as assessed by median survival and 1-year survival. There is a slight statistical superiority for cisplatin in terms of overall response rate, but this difference may not be clinically significant. There is a statistical trend towards a benefit in median survival in favour of cisplatin when the non-platinum drug is the same. No significant financial relationships to disclose.
Early Diagnosis of Ischemic Heart Disease
Authors: Joseph T. Doyle, A. Sandra Heslin, Herman E. Hilleboe, Paul F. Formel
Journal: New England Journal of Medicine (1959)

HALF of all deaths in the United States are ascribed to diseases of the circulation, the most important of which is arteriosclerotic, coronary-artery or ischemic heart disease.1 The term ischemic heart disease is preferred and will hereafter be used in this communication.2 Efforts to cure or to prevent ischemic heart disease are frustrated by ignorance of the etiology and the pathogenesis of the disease. The Cardiovascular Health Center, a prospective study of degenerative heart disease in a group of middle-aged men, was undertaken to extend knowledge of the natural history of ischemic heart disease, to exploit epidemiologic clues suggested by . . .
NTCT-04SPINAL CORD TOXICITY FROM INTRATHECAL CHEMOTHERAPY: A CASE WITH CLINICOPATHOLOGIC CORRELATION
Authors: David Dornbos, Pierre Giglio, Jose Otero, James Elder, Robert Baiocchi, Heather Cunningham, Wayne Slone, Vinay Puduvalli
Journal: Neuro-Oncology (2015)

We report antemortem pathologic and neuroimaging findings of severe myelotoxicity from intrathecal chemotherapy in a case of blastic plasmacytoid dendritic cell neoplasm (BPDCN) complicated by leptomeningeal disease. A 73 year old male was diagnosed with BPDCN after fine needle aspiration of an enlarged cervical lymph node. Total body PET imaging revealed extensive systemic hypermetabolic lymphadenopathy and a staging lumbar puncture was positive for malignant cells. He was treated with etoposide, vincristine, doxorubicin, cyclophosphamide, prednisone (EPOCH) and five doses of intrathecal cytosine arabinoside with the last dose administered on 2 months after diagnosis with CSF clearing. One year later, he developed progressive lower extremity weakness, numbness and bowel/bladder dysfunction. Lumbar spine imaging 4 weeks later revealed subtle linear enhancement along the cauda equina and within the dependent thecal sac, but cervical and thoracic spine MRI at this time were unremarkable. CSF showed atypical lymphoid cells and an Ommaya reservoir was placed. Intrathecal chemotherapy with methotrexate and cytarabine was started. Subsequent CSF analysis showed no malignant cells. However, the patient continued to have progressive ascending weakness and numbness, and his neurologic condition progressed to tetraplegia, low of bowel and bladder control and severe sensory loss, especially to vibration and joint position modalities. Spine MRI showed high signal intensity involving the posterior columns diffusely in the cervico-thoracic spinal cord. Metabolic and infectious work up was negative. A subsequent biopsy of the posterior columns of the lower thoracic spinal cord demonstrated cord destruction with profuse macrophage infiltration without evidence of malignant cells or microorganisms. Treatment with folate and cyanocobalamin resulted in no improvement, and the patient elected for palliative care only. This case illustrates central nervous system involvement by a rare myeloid tumor and demonstrates neuroimaging and unique antemortem pathology of intrathecal chemotherapy-induced myelotoxicity.
The effect of androgen deprivation therapy (ADT) on lipid and HbA1C parameters
Authors: J. Yannucci, J. Manola, M. Garnick, G. Bubley
Journal: Journal of Clinical Oncology (2005)

4562 Background: Studies suggest a reduction in prostate cancer-specific mortality with early versus delayed ADT. However, these same studies show no effect on overall mortality, raising the possibility of competing risk factors. Patients receiving ADT are known to be at increased risk for weight gain and truncal obesity, risk factors for insulin resistance and cardiovascular disease. In current practice, ADT is often administered prior to the development of clinical metastases and patients are treated for longer periods of time. Thus it is important to determine if ADT has an effect on lipid parameters. Methods: We analyzed a database collected during studies of Plenaxis compared to Lupron or to Lupron + Casodex. Patients were randomized in a 2:1 fashion to Plenaxis vs Lupron-based therapy. Fasting lipid profiles, glucose measurements, HbA1C levels and body weights were measured at baseline and on treatment days 85, 169. Fewer patients were available for analysis on days 253 and 336. 1,099 patients enrolled in the trial and 226 patients were on lipid lowering agents (statins) at the time of enrollment. One-sample t-tests were used to determine changes between baseline pretreatment values and each subsequent measurement for each treatment group and within each population (statins and no statins) using Bonferri-adjusted p-values of 0.01. Results: In all three treatment groups, there were significant increases in triglycerides, cholesterol and LDL between baseline and day 85 and baseline and day 169. There were also significant increases in HDL. All patients had increases in HbA1C from baseline to day 85. Only patients not on statins demonstrated statistically significant weight gain. No significant changes were observed in fasting glucose levels. Conclusions: ADT may affect both serum lipid values and HbA1C independent of statin therapy or the type of ADT. ADT may also result in increased HDL levels, thus the overall effect of ADT on serum lipids and cardiovascular risk is not certain. Although it is not possible to determine from this study whether these trends persist beyond 6 months, these data suggest that ADT therapy may be associated with risk factors for cardiovascular disease. Larger studies to investigate these parameters are warranted. No significant financial relationships to disclose.
Controversies in the Management of Regional Nodes in Melanoma
Authors: George Plitas, Charlotte E. Ariyan
Journal: Journal of the National Comprehensive Cancer Network (2012)

The surgical management of the regional lymph node basin of melanoma has undergone significant changes in the past 2 decades, most of which have been guided by prospective randomized trials. Historically, routine elective lymph node dissection was recommended for the management of melanoma regardless of clinical nodal involvement. Subsequent randomized trials failed to show a clear benefit for all patients, and sentinel lymph node (SLN) biopsy emerged as an alternative. Although the prognostic value of SLN biopsy in intermediate-thickness melanoma is well accepted, its value for patients with thin and thick lesions is debated. The therapeutic advantage of removing an involved SLN, and the need for a completion lymph node dissection after the identification of a positive SLN, are areas of continued controversy. This article discusses these issues in the management of the regional lymph node basin in patients with melanoma.
Bone and Joint Pain in Leukemia, Simulating Acute Rheumatic Fever and Subacute Bacterial Endocarditis
Authors: Mark Aisner, Thomas B. Hoxie
Journal: New England Journal of Medicine (1948)

ALTHOUGH pain along the bones and in the joints in the acute leukemias has been reported in the literature from time to time, its diagnostic significance has not been sufficiently stressed, and its confusion with acute rheumatic fever has been the rule rather than the exception. This confusion has depended to a large extent upon the many similarities in the symptomatology of the leukemias and rheumatic fever. In either of these conditions there may be asthenia, palpitation, dyspnea on exertion, epistaxis, fever, bone and joint pain, abdominal pain, pallor, purpuric manifestations, lymphadenopathy, splenomegaly, anemia, tachycardia, accentuation of the heart sounds . . .
Case 33-2009
Authors: Marc A. de Moya, Marcela G. del Carmen, Rae M. Allain, Ronald E. Hirschberg, Jo-Anne O. Shepard, Richard L. Kradin
Journal: New England Journal of Medicine (2009)

A 35-year-old woman was transferred to this hospital because of abdominal pain, fever, and hypotension 3 days after an elective cesarean section. On examination, she appeared acutely ill. The temperature was 39.2°C, the blood pressure 70/52 mm Hg, and the pulse 149 beats per minute. The abdomen was distended and very tender, with rebound. There was erythema and edema in the region of the surgical incision, extending to the left flank, with no drainage. A diagnostic procedure was performed.
Case 4-1997
Authors: Daniel M. Steigman, Eugene J. Mark
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 37-year-old man with the acquired immunodeficiency syndrome (AIDS) was admitted to the hospital because of dyspnea and wheezing of three months' duration.Nine years earlier, a test for antibodies against the human immunodeficiency virus (HIV) had been positive. Five years before admission, a tuberculin skin test (purified protein derivative, 5 TU) was positive, and isoniazid was administered for a year. Fourteen months and 10 months before admission, he was treated for Pneumocystis carinii pneumonia and thereafter received prophylactic doses of dapsone. He then felt well until three months before admission, when mild dyspnea and wheezing developed. . . .
Salt-Sensitive Essential Hypertension in Men
Authors: Theodore W. Kurtz, Hamoudi A. Al-Bander, R. Curtis Morris
Journal: New England Journal of Medicine (1987)

We investigated whether the anionic component of an orally administered sodium salt can influence the salt's capacity to increase blood pressure. In five men with essential hypertension in whom blood pressure was normal with restriction of dietary sodium chloride to 10 mmol per day (0.23 g of sodium per day), oral administration of sodium chloride for seven days, 240 mmol per day (5.52 g of sodium per day), induced significant increases in systolic and diastolic blood pressures, of 16±2 and 8±2 mm Hg (mean ±SEM) respectively (P<0.05). An equimolar amount of sodium given as sodium citrate induced no change in blood pressure. Replacing supplemental sodium chloride with an equimolar amount of sodium as sodium citrate abolished the increase in blood pressure induced by sodium chloride. Both salts induced substantial and comparable sodium retention, weight gain, and suppression of plasma renin activity and plasma aldosterone, but supplemental sodium chloride increased plasma volume and urinary excretion of calcium, whereas sodium citrate did not. These preliminary findings demonstrate that the anionic component of an orally administered sodium salt can influence the ability of that salt to increase blood pressure, possibly by determining whether the salt induces an increase in plasma volume. Our observations in a small group of men with salt-sensitive hypertension will require confirmation in larger numbers of patients of both sexes. (N Engl J Med 1987; 317:1043–8.)
Hyper-β-Alaninemia Associated with β-Aminoaciduria and γ-Aminobutyricaciduria, Somnolence and Seizures
Authors: C. R. Scriver, S. Pueschel, E. Davies
Journal: New England Journal of Medicine (1966)

A GREAT number of abnormal aminoacidurias have now been described,1 and investigation of such patients has provided better insight into normal human biology. We believe that the following report introduces three new problems of considerable interest:The presence of continuous hyper-β-alaninemia in a patient with somnolence and seizures may illustrate the pharmacologic effects of β-alanine on nervous tissue2; it also suggests that the tissue free pool of this compound is probably more actively regulated than previously suspected.Three β-amino compounds¶ — β-alanine, βAIB and taurine — were present in excessive amounts in urine whereas only β-alanine was elevated in . . .
Cardiopulmonary Insufficiency in Myotonic and Progressive Muscular Dystrophy
Authors: Kaye H. Kilburn, John T. Eagan, Herbert O. Sieker, Albert Heyman
Journal: New England Journal of Medicine (1959)

DESPITE the frequent occurrence of ventilatory insufficiency and congestive heart failure in myotonic and progressive muscular dystrophy,1 2 3 the cardiac and pulmonary disturbances in these disorders have rarely been evaluated. In myotonic dystrophy particularly, symptoms of acrocyanosis, hypersomnolence and lethargy have been noted for many years,4 5 6 but no physiologic explanation has been offered. An appraisal of the cardiopulmonary functions in muscular dystrophy was stimulated by our observations on a young man with nondisabling myotonic dystrophy who showed marked somnolence, hypercapnia, hypoxemia and Cheyne–Stokes respiration.7 This report describes the ventilatory functions, blood gas concentrations, effects of carbon dioxide and oxygen inhalation and . . .
Discussion on the Control of Diseases of Cattle Inimical to Man. Mastitis and Streptococeal Infections. Brucellosis and Sterility.
Authors: A. W. Stableforth, V. D. Allison, S. L. Hignett, R. Cruickshank, H. W. Steele-bodger, H. J. Parish, J. Francis, D. L. Hughes, A. D. Mcewen, S. J. Edwards, J. T. Edwards, A. T. R. Mattick, J. R. Barker, G. N. Gould, A. S. Parkes, J. Hammond, G. S. Wilson, S. J. Folley, N. J. Scorgie, L. E. A. Rowson
Journal: Journal of the Royal Society of Medicine (1942)
Ixabepilone given weekly in patients with advanced malignancies: Final efficacy and safety results of a phase I trial
Authors: N. Dickson, R. Peck, C. Wu, H. Burris
Journal: Journal of Clinical Oncology (2006)

2040 Background: Ixabepilone is a potent tubulin-targeting agent. The first epothilone analog, ixabepilone, has been developed to optimize the characteristics of the naturally occurring epothilone B. Methods: This open-label, single-arm Phase I dose escalation study was designed to establish the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), safety and a recommended dose of ixabepilone when administered as a weekly infusion to patients (pts) with solid tumors who had failed standard therapy. Eligible pts were aged ≥18 years and had histologically/cytologically confirmed solid tumor disease and an ECOG status of 0–2. Ixabepilone was administered weekly as a 30-minute infusion on a 21-day schedule. Due to neurotoxicity, infusion time was increased to 1 hour with a 1-week break allowed. Dosing ranged from 1–30 mg/m 2 . Tumor evaluations were performed every 6 or 8 weeks (21-day or 28-day schedule, respectively). Toxicity was evaluated continuously. Results: 34 pts were treated on the 21-day schedule (median age 55, range 30–73) and 52 on the 28-day schedule (median age 55, range 33–79). 88% of pts had received prior chemotherapy. Grade 3 fatigue was the DLT in 2 of the 4 pts treated with 30 mg/m 2 ixabepilone. No DLTs were seen at doses ≤25 mg/m 2 on the 21-day schedule, or at doses of 15, 20 or 25 mg/m 2 on the 28-day schedule. The MTD was 25 mg/m 2 for the 21-day schedule. Of 12 pts who received this dose and schedule, 7 (58%) experienced Grade 1/2 neuropathy, 1 (8%) developed Grade 3 sensory neuropathy and 3 (25%) experienced Grade 3 fatigue. Of 52 pts who received 20 mg/m 2 on the 28-day schedule, 2 (13%) had Grade 3 neutropenia, 1 (7%) had Grade 3/4 sensory neuropathy and 4 (27%) had Grade 3 fatigue. Five pts (two pts [21-day schedule], three pts [28-day schedule]) with breast, colon, ovary, head and neck tumors achieved objective partial responses. Conclusions: The recommended doses of ixabepilone from this study are 25 mg/m 2 (30-minute weekly infusion, 21-day schedule) and 20 mg/m 2 (1-hour weekly infusion, 28-day schedule). Ixabepilone demonstrated efficacy and an acceptable safety profile in pts with a broad range of tumor types, several of whom had failed a taxane. [Table: see text]
176P Safety analysis of chemotherapy for colitis-associated colorectal cancer in Japan
Authors: K. Nio, D. Higashi, H. Kumagai, S. Arita, T. Shirakawa, K. Nakashima, Y. Shibata, M. Esaki, T. Ueki, M. Nakano, H. Ariyama, H. Kusaba, M. Hirahashi, Y. Oda, T. Esaki, K. Mitsugi, K. Futami, K. Akashi, E. Baba
Journal: Annals of Oncology (2015)
Immunologic Function in Humans Before and After Hyperthermia and Chemotherapy for Disseminated Malignancy 2
Authors: R. J. DeHoratius, J. M. Hosea, D. E. Van Epps, W. P. Reed, W. S. Edwards, R. C. Williams
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Immunologic Function in Humans Before and After Hyperthermia and Chemotherapy for Disseminated Malignancy Get access R. J. DeHoratius, R. J. DeHoratius 4 4Address reprint requests to Dr. De Horatius at his present address: Department of Medicine, Jefferson Medical College, 1025 Walnut St., Philadelphia, Pa. 19107. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. M. Hosea, J. M. Hosea Search for other works by this author on: Oxford Academic PubMed Google Scholar D. E. Van Epps, D. E. Van Epps Search for other works by this author on: Oxford Academic PubMed Google Scholar W. P. Reed, W. P. Reed Search for other works by this author on: Oxford Academic PubMed Google Scholar W. S. Edwards, W. S. Edwards Search for other works by this author on: Oxford Academic PubMed Google Scholar R. C. Williams, Jr. R. C. Williams, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 4, April 1977, Pages 905–911, https://doi.org/10.1093/jnci/58.4.905 Published: 01 April 1977 Article history Received: 22 June 1976 Accepted: 26 August 1976 Published: 01 April 1977
<i>Mycoplasma pneumoniae</i>Infection in Families
Authors: Neron Balassanian, Frederick C. Robbins
Journal: New England Journal of Medicine (1967)

IT is now well established that primary atypical pneumonia is caused by Mycoplasma pneumoniae, the agent originally isolated by Eaton and often referred to as the "Eaton agent."1 2 3 4 5 In the past few years M. pneumoniae has been isolated from hospitalized and nonhospitalized patients of various ages with disease of both the upper and the lower respiratory tract.6 , 7 Outbreaks of primary atypical pneumonia in families, schools and military training camps have been described by many investigators.8 9 10 Jordan's8 study of 25 families suggested that the family is an important epidemiologic unit in the spread of the agent responsible for the disease. . . .