tbuckley/cabot-search huggingface dataset:
Aspirin Hepatotoxicity
Authors: A M Hilton, I W Dymock
Journal: Annals of Internal Medicine (1974)

Comments and Correction1 August 1974Aspirin HepatotoxicityANGELA M. HILTON, M.B., CH.B., M.R.C.P. (U.K), I. W. DYMOCK, M.B., M.R.C.P. ED., F.R.C.P. (GLASG)ANGELA M. HILTON, M.B., CH.B., M.R.C.P. (U.K)Search for more papers by this author, I. W. DYMOCK, M.B., M.R.C.P. ED., F.R.C.P. (GLASG)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-2-271 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The reports of aspirin-induced hepatotoxicity in patients with systemic lupus erythematosus (Ann Intern Med 80:1-8 and 80:74-76, 1974) show a clear relation between abnormal liver function and salicylate dosage. In three of the four patients described, liver biopsies were done when elevation of aminotransferases occurred. The biopsy specimens showed varied abnormalities, including one example of chronic active hepatitis. But in none of these cases was a repeat liver biopsy done when the biochemical changes had resolved after aspirin dosage was reduced.A recent study from this department of 30 patients with liver disease and joint symptoms*included...References1. MACKAYTAFTCOWLING ILD: Lupoid hepatitis and the hepatic lesions of systemic lupus erythematosus. Lancet 1:65-69, 1959 CrossrefMedlineGoogle Scholar2. DUBOIS E: Lupus Erythematosus. New York, McGraw-Hill Book Co., 1966, p. 129 Google Scholar3. REYNOLDSPETERSYAMADA TRS: Chronic active and lupoid hepatitis caused by a laxative, oxyphenisatin. N Engl J Med 285: 813-820, 1971 CrossrefMedlineGoogle Scholar4. TOGHILLSMITHBENTON PPP: Liver damage in patients taking methyldopa. Paper presented March 1974 to the British Society for Gastroenterology, Nottingham, England Google Scholar1. SEAMANPLOTZ WP: Aspirin hepatotoxicity in patients with rheumatoid arthritis or systemic lupus erythematosus (abstract). Clin Res 22:429A, 1974 Google Scholar2. SEAMANISHAKPLOTZ WKP: Aspirin and hepatotoxicity: addendum (letter). Ann Intern Med 80:279, 1974 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine University Hospital of South Manchester Withington Hospital West Didsbury Manchester M20 8LR England*HITLON AM, BOYES BE, SMITH PJ, et al: Liver disease in patients with joint symptoms. Unpublished. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHepatotoxicity Associated with Choline Magnesium Trisalicylate: Case Report and Review of Salicylate-Induced HepatotoxicityReactions of Carbon DioxideAntirheumatika und Leber 1 August 1974Volume 81, Issue 2Page: 271-272KeywordsAminotransferasesAspirinBiopsyChronic hepatitisLiverLiver diseasesLupus erythematosusSalicylates ePublished: 1 December 2008 Issue Published: 1 August 1974 PDF downloadLoading ...
Phase I study of intermittent dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor (IGF- 1R) and insulin receptor (IR) in patients with advanced solid tumors.
Authors: C. P. Carden, E. S. Kim, R. L. Jones, S. M. Alam, F. M. Johnson, A. W. Stephens, S. Poondru, R. Gedrich, S. M. Lippman, S. B. Kaye
Journal: Journal of Clinical Oncology (2010)

2530 Background: OSI-906 is a potent inhibitor of IGF-1R and IR tyrosine kinase activity. Increased IGF-1R activity is observed in human malignancies and implicated in resistance to chemotherapy. Methods: Patients (pt) with advanced solid tumors received escalating doses of OSI-906 in 3 intermittent dose schedules: (S1) days (d) 1-3 q14 d, (S2 - bridging cohort) d1-5 q14 d and (S3) d1-7 q14 d to determine safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor activity for S1 and S3. Results: 61 pt have been treated (29M: 32F, median age 60 yrs). Cohorts dosed: S1:10-750 mg; S2: 450 mg; and S3: 450 and 600 mg. Seven dose-limiting toxicities (DLTs) were observed: 4 pt with fasting grade 3 hyperglycemia (2 pt at 600 mg S1, 750 mg S1, and 600 mg S3), grade 4 fatigue (600 mg S3), grade 3 QTc interval prolongation and grade 3 vomiting (both at 750 mg S1). Most common drug related toxicities (any grade; grade 3) were; nausea (21%; 8%), vomiting (17%; 7%) and diarrhea (11%; 0%). PK results indicate linear exposure of OSI-906 with median Tmax and t3/4 of 1-8 and 2-5 hours, respectively. Plasma OSI-906 concentrations above the predicted efficacious concentration (1μ M) were achieved at MTD. PD effects related to growth hormone and IGF-1R/IR axes were observed and were associated with higher plasma OSI-906 concentrations. Twenty-four pt (39%) had stable disease for ≥ 12 weeks (w) including heavily pretreated NSCLC (43 w duration) and extraskeletal myxoid chondrosarcoma (84+ w duration). Of 11 adrenocortical carcinoma (ACC) pt treated, 1 pt with metastatic disease had a durable partial response (73% reduction by RECIST) of 64+ w duration, and 4 pt have stable disease at 12 w. Five ACC pts continue on study. Conclusions: MTD has been established in S1 and S3 at 600 mg QD. OSI 906 was well tolerated at doses up to MTD, and demonstrated dose proportional PK. PK and PD data indicate that OSI-906 concentrations sufficient for modulation of GH-IGF1 signaling axis were achieved. Preliminary antitumor activity was seen, particularly in ACC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI OSI OSI Genentech, OSI Genentech, OSI
Thrombolytic Therapy with Streptokinase in Acute Ischemic Stroke
Authors: The Multicenter Acute Stroke Trial — Europe Study Group
Journal: New England Journal of Medicine (1996)

In patients with acute ischemic stroke, early treatment with thrombolytic agents is thought to permit reperfusion of ischemic neurons and to promote recovery of function. The Multicenter Acute Stroke Trial — Europe (MAST-E) was designed to assess the efficacy and safety of streptokinase in patients with acute ischemic stroke.
Detection of circulating tumor cells in patients with renal cell carcinoma compared with a control group.
Authors: T. Gutschi, O. Pachernegg, K. Lackner, G. C. Hutterer, R. Stauber, K. Pummer, R. Zigeuner
Journal: Journal of Clinical Oncology (2010)

4618 Background: The spontaneous circulation of tumor cells is characteristic for invasive cancers. Currently no established tumor marker for renal cell carcinomas (RCC) is available. The relevance of circulating tumor cells (CTC) in RCC patients has not been systematically evaluated. The aim of this pilot study was to detect CTC in patients with RCC compared with a control group. Methods: After IRB approval, blood samples of 22 patients affected by a renal tumor were taken pre- and intraoperatively. 5 patients with benign renal diseases and no evidence of other malignancies served as control group. Epithelial tumor cells were isolated using the ISET (Isolation by Size of Epithelial Tumor cells) method. A specific filter captures cells larger than 8 μ m in diameter out of full blood, including CTC. Enriched cells were stained on the filters and CTC were counted after cytopathological evaluation by one pathologist blinded to the diagnoses, enriched cells were studied by immunolabelling. Detection of CTC in at least one out of two blood samples was considered positive. Positive and negative findings were compared with the final histological diagnosis, and sensitivity, specificity, positive and negative predictive values of the ISET method were recorded. Results: 19/22 tumors were confirmed as RCC. The 3 patients with non-malignant lesions (2x angiopmyolipoma, 1x oncocytoma) were included in the control group which finally consisted of 8 patients. Overall, CTC were detected in 15/27 patients. 12/15 CTC-positive patients had histologically confirmed RCC, whereas 3/15 patients had false-positive findings. In the remaining 12 patients with no evidence of CTC, RCC was diagnosed in 7 cases. 2/4 patients presenting with metastatic disease were CTC positive. Overall, specificity and sensitivity for ISET were 63% each. Positive and negative predictive values were 80% and 42%, respectively. Conclusions: In this pilot study, a positive predictive value of 80% was recorded for detection of CTC in RCC patients warranting further investigations. If confirmed by subsequent studies in larger cohorts, the ISET method might have a potential role as a marker for RCC. No significant financial relationships to disclose.
Can meta-analysis suggest carboplatin/paclitaxel as a reference arm in randomized trials of first-line chemotherapy for advanced non-small cell lung cancer?
Authors: T. Yamanaka, N. Yamamoto, T. Seto, T. Takahashi, H. Murakami, A. Tsuya, T. Naito, K. Kaira, Y. Nakamura, Y. Ichinose
Journal: Journal of Clinical Oncology (2009)

e19039 Background: The validity of adapting carboplatin/paclitaxel (CbP) as a reference arm in randomized trials of first-line chemotherapy for advanced non-small-cell lung cancer has not been fully evaluated. Methods: We performed a meta- analysis on trials identified through a literature search. The analysis included randomized trials comparing CbP with cisplatin-based third- generation (3G) regimens. Results: Of 160 articles screened, seven randomized trials were eligible for the analysis. The pooled hazard ratio (HR) for overall survival showed that CbP was not an inferior regimen to cisplatin-based 3G regimens (HR=1.04; 95% confidence interval, 0.96–1.13; p=0.296). On focusing on 3G agents other than vinorelbine, we observed a marginally significant improvement in survival with cisplatin-based regimens (HR=1.08; 95% confidence interval, 0.99–1.18; p=0.080). CbP generally involved a higher risk of thrombocytopenia and peripheral neuropathy but a lower risk of anemia, nausea, and toxic deaths. Conclusions: There is no evidence that CbP was significantly inferior to cisplatin-based 3G regimens in terms of efficacy. However, since CbP was less inclined to result in better survival, the preferred use of CbP as a reference arm in randomized trials instead of cisplatin-based 3G regimens may depend on the purpose of the trial. No significant financial relationships to disclose.
Daunorubicin versus mitoxantrone for induction therapy of patients of de novo acute myeloid leukemia
Authors: L. Varadpande, S. Rajappa, N. Naidu, R. Digumarti
Journal: Journal of Clinical Oncology (2008)

7076 Background: Recent studies suggest that higher doses of Daunarubicin (DNR) may lead to better complete remission (CR) in patients with de-novo acute myeloid leukemia (AML). Most studies have used DNR at doses ranging from 30–45mg/m2. To our knowledge, there are no randomised comparisons of higher doses with mitoxantrone (MXN). This study was undertaken as a preliminary trial to compare the CR rates and toxicity of 60 mg/m2 of DNR compared with MXN. Methods: Seventy newly diagnosed de-novo AML patients were randomized to either DNR 60mg/m2 (group A) or MXN 12 mg/m2 (group B) for days 1–3 along with Ara-C 100mg/m2 as a continuous infusion days 1–7. Those with ECOG PS > 3, age > 60 years and AML M3 were excluded. The primary endpoint was CR rate and secondary endpoints were induction mortality, transfusion requirements and duration of grade 3 or 4 cytopenias. The trial had 80% power to detect a 10% difference in the CR rates. Results: Sixty-eight patients were evaluable, 35 in Group A and 33 in Group B. The groups were comparable for demographic, hematological and cytogenetic parameters. Twenty-two (63%) patients in Group A and 20 (61%) in Group B achieved CR (p=1.0). Four patients (11%) in Group A and 8 (25%) in Group B died due to uncontrolled sepsis (p=0.21). There was no significant difference with respect to major organ toxicities, duration of grade 3 or 4 neutropenia (p=0.67) and thrombocytopenia (p=0.40), platelet transfusions (p=0.80) and duration of admission (p=0.72) between the groups. The requirement for packed red cell (PRC) transfusion was significantly higher in Group B (p=0.05). Among those who attained CR, 18 patients in Group A and 14 patients in Group B received high dose Ara-C (HIDAC 3 g/m2 bid days 1,3 & 5) as consolidation. None underwent stem cell transplantation. The median relapse free survival of patients who received HIDAC was 171.5 days (range, 50–650) for Group A and 192.5 days (range, 45–789) for Group B (p=0.669, log rank test). Conclusion: The CR rates with higher doses of DNR were not superior to MXN. The adverse events, duration of cytopenias and hospitalization were similar. Patients on MXN arm required more PRC transfusions. No significant financial relationships to disclose.
Average length of stay in hospice for five types of cancer
Authors: D. Tanis, B. Kinzbrunner
Journal: Journal of Clinical Oncology (2007)

17038 Background: Factors which influence average length of stay (ALOS) for cancer patients who choose hospice include patient and family preferences, availability of hospice services, demographics, specialty and experience of referring physician, advances in treatment options, and type of cancer. In this paper, we examine trends in ALOS for the top five cancers in patients who utilized a large, national hospice provider between 2000 and 2006. Methods: We examined 61,457 patients with prostate, colorectal, breast, lung, or pancreatic cancer who were admitted to one of 40 hospice programs and died on service between 1/1/2000 and 11/30/2006. The top five cancers accounted for 58% of all cancer deaths in the Vitas programs. The effect of Type of Cancer and Year on ALOS was evaluated using analysis of variance. Pair-wise differences were compared using the Bonferroni correction. Results: Overall ALOS was 40.6 days. ALOS for prostate, colorectal, breast, lung and pancreas was 47.9, 45.6, 45.5, 37.8 and 31.7 days, respectively. Prostate, colorectal and breast ALOS were not significantly different from one other; lung ALOS was significantly less than the top three (p &lt; .001); and pancreas ALOS was significantly lower than all others (p &lt; .001). There was no evidence of yearly trends in ALOS for different cancers during the study period. Conclusions: ALOS for patients with one of the five leading cancers who elected hospice services prior to death has remained remarkably stable over the last seven years. This stability, combined with an overall ALOS of less than six weeks, suggests that much still needs to be done to maximize cancer patient utilization of hospice services. The somewhat longer ALOS for patients with prostate, colorectal and breast cancer may be related to differences in natural history and effectiveness of anti-neoplastic therapies when compared to cancers of the lung and pancreas. No significant financial relationships to disclose.
Outcome of the nonrandomized patients in the FFCD 9102 trial: Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus
Authors: J. Jouve, P. Michel, C. Mariette, F. Bonnetain, O. Bouché, T. Conroy, D. Pezet, P. Burtin, P. Segol, L. Bedenne
Journal: Journal of Clinical Oncology (2008)

4555 Background: For locally advanced thoracic oesophageal cancers, the FFCD 9102 trial have demonstrated that for responders chemoradiation only was equivalent to chemoradiation followed by surgery in term of overall survival. What about nonrandomized patients (Bedenne L et al. J Clin Oncol 2007;25:1160–8)? Methods: Out of 451 patients, 192 were not randomized because of no objective response or improved dysphagia, contraindication to either surgery or continuation of chemo-radiation, patient’s refusal, death or no further treatment. Results: At the end of the induction chemo-radiation, there was no difference between randomized and non-randomized patients in term of age, tumor height and diameter, doses of chemotherapy or radiotherapy. However, weight loss, body surface and Spitzer QoL Index were significantly different. Duration of follow-up was identical: 47.3 months vs 48.1 months (NS). Overall survival was significantly lower in non-randomized patients: median survival 11.5 months (SE = 1.09 months) vs 18.9 months (SE = 1.03 months) in randomized patients (HR = 1.40 [95%CI, 1.13 to 1.74], p = 0.0024). In the non-randomized group 112 patients were operated on, among them 80 had R0 resection (42%). For all patients operated on median survival was 17.3 months (SE = 0.65 months) versus 6.1 months (SE = 0.46 months) in non-operated patients (p < 0.0001), and was not different from survival of the randomized ones (p = 0.58). Conclusions: Surgery is a valuable option for patients non responding to a planned exclusive chemoradiation therapy. No significant financial relationships to disclose.
Evaluation of clinical significance of basal-like subtype of breast cancer identified by immunohistochemistry
Authors: L. B. Cassol, M. Graudenz, A. Zelmanowicz, A. Cancela, C. Coral, G. Yser, B. Garicochea
Journal: Journal of Clinical Oncology (2007)

21107 Background: At present time, prognostic evaluation of initial breast cancer is mostly based on patients’ clinical and tumoral histological features. Recently, molecular subtypes of invasive breast cancer were recognized through DNA microarray profiling studies. This new classification can potentially improve the prognostic evaluation but this technology is still not widely available. The possibility of identifying the molecular subtypes through simpler and cheaper methods is promising. The identification of basal-like breast cancer (BLBC) is particularly important because it has a poor outcome and fewer treatment options available. Additionally, Epidermal Growth Factor Receptor (EGFR) expression seems to be more frequent in this subtype. Methods: A retrospective cohort of 112 consecutive patients with pathologic stage I or II primary breast carcinomas, treated in the same institution between 1995 and 2000, was studied. Histological and clinical features as well as clinical outcome and survival were reviewed. Immunohistochemical analysis was carried out in representative blocks of tumors with antibodies against Estrogen Receptor (ER), Human Epidermal Growth Receptor - type 2 (HER2), CK5/6 and EGFR. The primary endpoint was to determine the prevalence of BLBC (ER and HER2-negative and CK 5/6 and/or EGFR-positive) in this population. Results: 13 of 112 tumors (11,6 %) were BLBC. Their mean age was 49 years; 77 % were stage II and 100 % were invasive ductal carcinomas. There was no prognostic difference between BLBC and the subtypes luminal (ER-positive and HER2-negative); HER2-overexpressing (HER2-positive) and undetermined (four markers negative) relating to disease-free and overall survival. This is probably related to limited number of patients in this study and good prognosis of initial-stage patients. 11 of 112 cases (10%) were positive for EGFR. EGFR-positive tumors tended to be ER- negative (23 % vs 5 %; p=0,01). Conclusions: Our results suggest that it is possible to identify BLBC by immunohistochemical analysis of ER, HER2, CK 5/6 and EGFR. Besides, EGFR expression seems to be more frequent in ER-negative tumors, which suggest EGFR-targeted drugs may benefit this population. No significant financial relationships to disclose.
Preliminary results of a prospective study of 18F-NAF PET/CT in prostate cancer.
Authors: Jong Chul Park, Karen A. Kurdziel, Liza Lindenberg, James L. Gulley, Ravi Amrit Madan, Lauren V. Wood, Yolanda McKinney, Peter L. Choyke, William L. Dahut, Andrea Borghese Apolo
Journal: Journal of Clinical Oncology (2013)

103 Background: We performed a prospective study of 18 F-NaF PET/CT bone scan (NaF) in the detection of bone metastases in men with prostate cancer. We previously reported that NaF identified more malignant lesions than Technetium-99m MDP bone scan (TcBS) (ASCO 2012 10589). This study evaluates the ability of NaF to detect bone metastasis in men with normal TcBS and also explores the change in NaF over 6 and 12 months compared to PSA changes. Methods: In a prospective 2-arm study, 60 men with prostate cancer (30 with and 30 without bone metastases by TcBS) were studied (ages 51-79). All had NaF and TcBS at baseline, followed by repeat NaF at 6 and 12 months. TcBS and NaF were reviewed by experienced nuclear medicine physicians. Abnormal foci of uptake on TcBS and NaF were classified as benign, malignant or indeterminate. Malignant uptake on NaF was confirmed by characteristic osteoblastic features on CT. Scan results were categorized as “positive” if any malignant lesion was present. In the 6 and 12 months follow up NaF, results were categorized as progression of disease (PD) = any new lesions or SUV increase &gt; 30% in known lesions; stable disease (SD) = no new lesions or SUV changes &lt; 30% in known lesions; and improvement of disease (ID) = resolution of known lesions or decrease SUV &gt; 30% in known lesions. Results: 60 men have enrolled on study, 58 and 34 completed 6 and 12 month follow-up respectively. At baseline, 14 of 30 (47%) men with negative TcBS showed evidence of bone metastases in NaF (PSA mean 45); 7/14 had 2 baseline NaF and showed positive results in both, demonstrating reproducibility; 13/14 and 7/14 had follow up NaF at 6 and 12 months, respectively, all of which remained positive. In follow-up, 13/58 men at 6 months and 8/34 men at 12 months had PD from baseline on NaF, of whom 5/13 (38%) at 6 months and 5/8 (63%) at 12 months also had a PSA increase &gt; 50%. All men who had PD on NaF at 6 months and had a follow-up scan at 12 months remained positive. 15 men at 6 months and 7 men at 12 months had ID on follow-up NaF, of which 11/15 (73%) and 6/7 (86%) had PSA decrease &gt; 50% at 6 and 12 months, respectively. Conclusions: Early results of this ongoing NaF study are encouraging and suggest NaF identifies metastatic bone disease earlier than TcBS and correlates with changes in PSA. Clinical trial information: NCT01240551.
Cilengitide (Cil) Combined with Cetuximab and Platinum-Based Chemotherapy As First-Line Treatment in Advanced Non-Small Cell Lung Cancer (Nsclc) Patients (Pts): Phase Ii Randomised Certo Study
Authors: J.F. Vansteenkiste, F. Barlesi, C. Waller, J. Bennouna, C. Gridelli, E. Goekkurt, D. Verhoeven, A. Szczesna, M. Feurer, J. Milanowski, P. Germonpre, H. Lena, D. Atanackovic, M. Krzakowski, C. Hicking, J. Straub, M. Picard, W. Schuette, K. O' Byrne
Journal: Annals of Oncology (2014)