tbuckley/cabot-search huggingface dataset:
Technetium 99m-labeled IMMU-4, a monoclonal antibody against carcinoembryonic antigen, for imaging of occult recurrent colorectal cancer in patients with rising serum carcinoembryonic antigen levels.
Authors: Y Z Patt, D A Podoloff, S Curley, L Kasi, R Smith, V Bhadkamkar, C Charnsangavej
Journal: Journal of Clinical Oncology (1994)

PURPOSE We tested whether nuclear imaging with technetium 99m-labeled murine monoclonal antibody (MoAb) against carcinoembryonic antigen (CEA) IMMU-4 will detect recurrent colorectal disease in patients with a rising serum CEA level but negative abdominal and pelvic computed tomographic (CT) scan, chest radiograph, and colonoscopy, or barium enema. PATIENTS AND METHODS Sixteen patients with completely resected, CEA-producing colorectal cancer were given 1 mg of 99mTc-labeled IMMU-4 intravenously with no toxic side effects. Planar and single-photon emission CT (SPECT) scans were acquired at 6 hours. Fifteen patients underwent an exploratory laparotomy at 24 hours. Results of the scintigraphy were correlated with surgical findings. RESULTS Twelve of 15 patients (80%) had true-positive (TP) scans when correlated with surgery. Two of 15 (13%) had true-negative (TN) scans inasmuch as exploratory laparotomy failed to detect recurrent disease. A false-positive (FP) scan was obtained in one of 15 (7%). There were no false-negative (FN) scans. Sensitivity, specificity, accuracy, and the positive predictive value (PPV) were 100%, 67%, 93%, and 92%, respectively. Twenty-six histologically confirmed areas of malignancy were found and correlated with areas of increased activity seen on IMMU-4 scintigraphy. Twenty-one were TP; five were not detected by scintigraphy and were thus considered to be FN. There were five FP lesions and 25 TN regions. Sensitivity, specificity, accuracy, and the PPV in these 26 cancer tissues were 81%, 83%, 82%, and 81%, respectively. The median radioactivity ratio of tumorous tissue to normal tissue was 3.33, with a range of 0.89 to 17.16. CONCLUSIONS These results suggest that 99mTc IMMU-4 scintigraphy is an important addition to the armamentarium available for diagnostic imaging and may help detect occult metastatic cancer missed by abdominal and pelvic CT in patients with rising CEA levels.
A multivariate analysis for the survival of nodal peripheral T-cell lymphoma (PTCL)
Authors: M. Oki, M. Isozaki, N. Nakamura, A. Kikuchi, T. Tsuchiya, P. Arbogast, Y. Ogawa, K. Ando
Journal: Journal of Clinical Oncology (2009)

e19521 Background: Nodal peripheral T-cell lymphoma (PTCL) is uncommon lymphoma with various subtypes and poor prognosis. There is no definitive therapeutic improvement by conventional chemotherapy (CT) for decades. However, the superiority of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has remained inconclusive. The infrequency of PTCL is an obstacle to perform a large prospective study. We conducted a retrospective study of fifty six patients with three major nodal PTCL, histologically classified as PTCL-not specified (NOS, n=29), angioimmunoblastic T-cell lymphoma (AITL, n=19), and ALK-negative anaplastic large cell lymphoma (ALCL, n=8) who underwent ASCT (n=14) or not (n=42) after CT in Tokai University Hospital, Ebina General Hospital, and Hadano Red Cross Hospital, Kanagawa, Japan between 1997 and 2008. We determined whether international prognostic index (IPI), serum soluble IL-2 receptor level (sIL-2R) and ASCT were correlated with the survival. Methods: Retrospective, multicenter cohort study by time-dependent or non-time-dependent multivariate survival analysis with Cox proportional hazard regression. Results: Median age was 61 (18–81). The percentage of IPI more than 3 was 50. Median sIL-2R was 4120 ng/ml. (311–96,800). In non-time-dependent analysis, both ASCT and sIL-R were significant prognostic factors for overall survival (OS). Hazard ratio (HR) of ASCT, IPI, and sIL-2R were 0.24 (95%CI: 0.08–0.76, p=0.02), 0.77 (95%CI: 0.34–1.77, p=0.54), and 1.45 (95%CI: 1.129–1.857, p=0.035), respectively. But in time-dependent manner, the significant effect of ASCT was offset for OS. HR of ASCT was 0.82 (95%CI: 0.25–2.71, p=0.75). Only sIL-2R was still statistically significant, which HR was 1.31 (95%CI: 1.04–1.66, p=0.03). On the other hand, ASCT was only important effect on progression-free survival (PFS) by non-time-dependent analysis, which HR was 0.20 (95%CI: 0.07–0.55, p=0.02). After time-dependent analysis, no variates influenced PFS. Conclusions: The OS advantage of high-dose chemotherapy followed by ASCT is offset by time-dependent Cox proportional hazard analysis. The level of sIL-2R has impact on OS. Prospective multicenter randomized trial will be needed to show or not to show an advantage for ASCT. No significant financial relationships to disclose.
Comparison of lung expansion techniques on thoracoabdominal mechanics and on incidence of pulmonary complications after abdominal surgery: A randomised controlled trial
Authors: Adriana Lunardi, Denise Paisani, Cibele Marques da Silva, Desiderio Cano, Celso Carvalho
Journal: European Respiratory Journal (2014)

Lung expansion techniques (LET) are widely used to prevent postoperative pulmonary complications (PPC). However, the effect of each of these techniques on thoracoabdominal mechanics and its relationship with the incidence of PPC after abdominal surgery remain unclear.  HYPOTHESIS : The LET that promotes higher chest wall volume with lower respiratory effort would be better to prevent PPC.  OBJECTIVE : To compare the effect of LET on pulmonary volumes, respiratory muscle activation and incidence of PPC after abdominal surgery.  METHODS : This randomised and controlled trial enrolled 137 patients randomly assigned into 4 groups: control (n=35), volume incentive spirometry (n=34); flow incentive spirometry (n=33) and deep breathing (n=35). Intervention groups performed 50 repetitions of specific technique, 3 times a day during 5 days. PPC (pneumonia or atelectasis or severe hypoxemia) were analysed by a blinded evaluator until hospital discharge. Chest wall volume (via optoelectronic plethysmography) and sternocleidomastoid and superior and inferior intercostal muscles activation (via electromyography) were assessed before and 3 days after surgery, during baseline and deep breathings. ANOVA and chi-square were tested considering intention to treat.  RESULTS : Groups were homogenous for age, gender, BMI and lung function. After surgery, all groups were similar on chest wall volume variation and respiratory muscle activation. The incidence of PPC was higher on deep breathing group (pl0.05).  CONCLUSION : LET have similar effect on thoracoabdominal mechanics and do not prevent PPC in patients undergoing upper abdominal surgery.
Expression of the familial Mediterranean fever gene and activity of the C5a inhibitor in human primary fibroblast cultures
Authors: Yaacov Matzner, Suzan Abedat, Eli Shapiro, Shlomit Eisenberg, Ariela Bar-Gil-Shitrit, Polina Stepensky, Sima Calco, Yehudit Azar, Simcha Urieli-Shoval
Journal: Blood (2000)
A prospective, open-label, randomized phase II trial to evaluate the changes of bone resorption marker after administration of zoledronic acid (ZOL) in nasopharyngeal cancer (NPC) patients with bone metastases (BM)
Authors: Y. Zhao, H. Liao, X. Hou, J. Sun, Y. Guo, S. Li, L. Zhang
Journal: Journal of Clinical Oncology (2009)

6063 Background: ZOL is the only bisphosphonate that has demonstrated efficacy for the prevention of skeletal-related events (SREs) in patients with BM in a wide range of tumor types. Recent retrospective analyses also showed that normalization of N-telopeptide of type I collagen (NTX) over 3 months by the treatment of ZOL provided a continuum of SRE risk reduction and survival benefit in patients with BM (Lipton et al. ASCO 2007). Therefore, we conducted the prospective open-label randomized phase II trial to evaluate the changes of NTX after administration of ZOL in NPC patients with BM. Methods: Newly diagnosed NPC patients with BM were randomized to receive chemotherapy of cisplatin (20mg/m 2 IV, D1–5) plus FU (500mg/m 2 IV, D1–5) (CF regimen, q3wks) and intravenous ZOL (4mg, q4wks, for 3months, CF+ZOL Group) or the same chemotherapy alone (CF Group). Urinary NTX was measured by ELISA method (Coleman et al. JCO 2005) at baseline and 1, 2, 3 months after administration of ZOL in all patients. Results: Sixty patients were enrolled into the study, 30 patients in each group. The median chemotherapy cycles was the same (4 and 4, respectively) in two groups. The median baseline NTX level had no difference between the two groups (75.4 vs. 95.6 nM BCE/mM creatinine, respectively p&gt;0.05). The NTX decreased 65.9% within 1 month in CF+ZOL group, whereas NTX increased 2.61 % in CF group (p&lt;0.01). The median NTX decrease percentage in 2,3 months after treatment were 70.8%, 86.5% in CF+ZOL Group and 15.9%, 34.5% in CF Group respectively (p&lt;0.01, p&lt;0.01). Conclusions: ZOL administered with chemotherapy (CF) consistently reduced NTX levels in NPC patients with BM, indicating potential benefit of ZOL may exist in this group of patients. The value of NTX reduction in NPC patients with BM need to be further studied in larger prospective randomized trials. [Table: see text] [Table: see text]
Treatment of Kaposi's sarcoma: overview and analysis by clinical setting.
Authors: C Odajnyk, F M Muggia
Journal: Journal of Clinical Oncology (1985)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1985.3.9.1277 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2411882 Treatment of Kaposi's sarcoma: overview and analysis by clinical setting. C OdajnykxC OdajnykSearch for articles by this author , F M MuggiaxF M MuggiaSearch for articles by this author https://doi.org/10.1200/JCO.1985.3.9.1277 First Page PDF © 1985 by American Society of Clinical Oncology
Phase I study of sunitinib malate continuously dosed and standard-infusion gemcitabine in solid tumors
Authors: J. M. Brell, J. A. Bokar, M. M. Cooney, S. S. Krishnamurthi, J. Gibbons, C. J. Nock, P. Savvides, E. Batts, S. P. Ivy, A. Dowlati
Journal: Journal of Clinical Oncology (2008)

13533 Background: Sunitinib malate (S) is an oral multi-targeted tyrosine kinase inhibitor (TKIs) with affinity for VEGFRs, PDGFRs, KIT, RET, and Flt3. These targets are significant in several malignancies based on pre-clinical and clinical data. Cytotoxic chemotherapy and targeted angiogenesis inhibition concomitently may enhance tumor control. In this phase I trial gemcitabine (G) was combined with S in a continuous dosing schema to assess maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and tumor response. Methods: Eligible patients had no curative therapy options, adequate organ function, and no prior anti-angiogenic treatments. The first dose level administered G 800 mg/m2 intravenously (IV) weekly×3 every 28 days and S 25 mg orally every day. Any treatment-related grade 4 toxicity, grade 3 cardiac or venous thrombosis, unresolved non-cardiac grade 3 event, or uncontrolled hypertension was defined as DLT. Results: Six patients (3 unresectable pancreas,1 metastatic pancreas, 1 pleural mesothelioma, 1 germ cell) with a median age of 65 years (range 39 to 73) and ECOG performance status of 0 - 2 were treated on dose level one. Only the mesothelioma and germ cell patients had prior therapy. Patient 2 experienced DLT of asymptomatic neutropenia, requiring expansion of the cohort; no further DLTs were seen at this dose level. Other toxicities included grade 4 dyspnea due to progressive disease and grade 3 hyponatremia, hypokalemia, and neutropenia, experienced by one pateint each. Two patients had grade 3 leucopenia. Two of the unresectable pancreas patients experienced confirmed partial responses (PRs). Patients are accrued to dose level two (S 37.5 mg orally per day and G 800 mg/m2 IV weekly × 3 every 28 days). Conclusions: Continuous dosing of S with G appears tolerable. Safety monitoring continues; it is anticipated that higher dose levels will have greater myelosuppression based on known mechanisms of action. Two unresectable pancreas cancer patients have confirmed PRs; the regimen merits continued assessment in this population. Supported by NIH/Cancer Therapy Evaluation Program U01 CA62502. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology Eli Lilly, Genentech™ BioOncology Celgene, Genentech™ BioOncology, GlaxoSmithKline, Pfizer Oncology
Oral vinorelbine (NVBO) in combination with trastuzumab (HER) in metastatic breast cancer (MBC): Data on efficacy and safety when administered in first- or second-line treatment.
Authors: J. J. Illarramendi, I. Blancas, P. Bueso, F. Carabantes, E. Polo Marques, E. Ciruelos Gil, M. Corral, F. J. Perez
Journal: Journal of Clinical Oncology (2010)

e11508 Background: Vinorelbine plus HER is an active and well-tolerated regimen in HER2-overexpressing MBC. When HER is administered every 3 weeks, the use of oral vinorelbine can increase the patient's convenience avoiding local toxicity. We report the retrospective results of our clinical experience on the combined regimen of HER and NVBO as first- or second-line treatment in HER2+ MBC. Methods: Between April 2005 and March 2009, 18 patients (p) with histologically confirmed, measurable MBC were treated in 8 Spanish institutions. Tumors scored as +3 positive for HER2 by inmunohistochemistry or FISH+. P could have received a prior treatment line with HER plus chemotherapy (CT). Treatment consisted of HER 8 mg/kg as a loading dose, then 6 mg/kg i.v. every 3 weeks, plus NVBO 80 mg/m2 days 1 and 8, with a prior test of myelosensitivity at 60 mg/m2 for the first cycle (cy), every 3 weeks. Treatment was continued until progression or unacceptable toxicity. Results: Patient's characteristics were: PS 0-1, 94%; visceral involvement in 100%; >2 metastatic sites in 50%. Prior (neo)adjuvant CT in 11 p (61%); type of CT: anthracycline 63%, anthracycline+taxane 27%. Prior hormonetherapy, 9 p (50%). Treatment was administered as first-line CT in 8 p (44%); second-line CT in 10 p (56%). Median number of cy 6 (range 3-12). We analyzed 121 cy. NVBO dose reduction was performed in 2.9% cy on D1 and 1.6% cy on D8. Hematological toxicities (%cy): grade (g) 3 anemia, 0.8%; no g3-4 neutropenia was reported. Nonhematological toxicities (%cy): g3 asthenia, 0.8%; g3 diarrhea, 3.3%; g3 nausea/vomiting 1.7%. All patients were evaluable for response. 5 CR (28%), 6 PR (33%), and 5 SD (28%) were reported. Objective response (OR) rate 61%. Median follow-up was 4.3 months (range 2.3-17.03), At the time of analysis, 3 p presented PD and 1 p had died. Conclusions: The findings of this retrospective analysis when compared to the reported data in the literature in this population suggest that the combination of three-weekly HER plus oral vinorelbine (80 mg/m2 D1 and 8) has a similar efficacy when compared to i.v. vinorelbine while avoiding venous toxicity and adding comfort to the day 8 administration. No significant financial relationships to disclose.
Population pharmacokinetics of docetaxel in elderly patients
Authors: S. Uriens, K. Rezai, V. Girre, V. Dieras, F. Lokiec
Journal: Journal of Clinical Oncology (2007)

13020 Background: Elderly patients (&gt;70 years) may present different pharmacokinetic profile for many drugs , mainly because of altered elimination due to renal function or metabolic decreases. Methods: Docetaxel, 50 to 85 mg/m 2 , median 70 mg/m 2 , was infused during 1 hr to 44 patients, aged 70 to 83 years, median 76.5 years. Three blood samples per patient were obtained according to a limited sampling strategy (Baille et al. Clin Cancer Res 1997, vol. 3, 1535–38). Covariates of interest were carefully recorded, age, body weight, body surface area, gender, serum creatinine, orosomucoid, serum albumin. These data were then analysed using NONMEM V to a) obtain individual Bayesian estimates of docetaxel clearance, b) re-analyse the data in order to estimate population parameters for this elderly population, c) show possible covariate effects on the pharmacokinetic parameters. Results: Median docetaxel CL from Bayesian estimation was 29.1 (2.5–97.5% quantiles 12–49) L/h. When the population was re-analysed per se, docetaxel CL was 29.2 (2.5–97.5% quantiles 17–35) L/h. The inter- subject variability for CL was 25% (precision 32%).. No covariate effect was observed on CL. Conclusions: Docetaxel clearance in elderly patients is slightly decreased, 29 L/h versus 36.8 L/h (reported in 547 patients, mean age 56 years, 5–95% quantiles 39–71 years). The inter-subject-variability of CL in elderly patients was decreased to 25% versus 47.5% in the 547 patients population. A pharmacokinetic- pharmacodynamic modelling of neutrophil counts versus time will be performed in these elderly patients in order to point a possible different sensitivity of this population to the myelosuppressive effects of docetaxel. No significant financial relationships to disclose.
A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy
Authors: MS Gordon, WJ McCaskill-Stevens, LA Battiato, J Loewy, D Loesch, E Breeden, R Hoffman, KJ Beach, B Kuca, J Kaye, GW Jr Sledge
Journal: Blood (1996)
Abstract 12688: Long Term Use of Calcium Channel Blockers and Risk of Breast Cancer Development
Authors: Uyen T Lam, Stacey Knight, Tami L Bair, Viet T Le, Joseph B Muhlestein, Jeffrey L Anderson
Journal: Circulation (2014)

Introduction: Calcium channel blockers (CCBs) are a mainstay in treating hypertension (HTN). Recently, Li et-al published a population based case-control study (JAMA 2013; 289:2354) reporting CCB use to be associated with incident breast cancer (odds ratio 2.6). We prospectively analyzed 2 Intermountain Healthcare (IHC) databases (db) to confirm or refute this provocative report. Methods: Two separate analyses were conducted using general patients (GP) seen at IHC and patients undergoing coronary angiography (CV) at IHC facilities. Subjects were females aged 50-70 with no history of breast cancer. Those prescribed CCB were matched 1:1 to subjects not on CCB based on age, race, tobacco, alcohol, body mass index, HTN and follow up time. Multivariable Cox proportional hazards regression was used for the primary analysis of time to incident breast cancer by CCB use adjusting for history of other cancers and family history of breast cancer. Results: A total of 2612 GP subjects (cases/controls) and 1106 CV subjects (cases/controls) were studied. In the GP db, there was a statistically significant increased risk of breast cancer for subjects using CCB (HR=1.58; 95% CI: 1.10-2.26). Risk was also associated with a positive family history (HR=2.79; 1.96-3.97) and a personal history of cancer (HR=1.87; 1.07-3.26). Breast cancer predominantly developed in &lt;5 y of follow up (64% of cases). However, a reverse relationship was found in the CV db, where the HR was 0.51 (95% CI: 0.27-0.97). This observation was found despite consistent associations with several secondary outcomes, including for incident diabetes, coronary and renal disease. Conclusion: A modest association between CCB use and incident breast cancer was observed in the GP db, but results were not reproducible in the CV db. Given lack of a credible mechanism and failure of previous randomized CCB studies to detect a signal, we interpret these modest and conflicting associations to likely represent uncorrected confounding, e.g. prescriber bias or drug interactions. Similarly, we believe the results of Li et-al may represent confounding. Given the important role of CCBs in clinical medicine, further studies are warranted, including randomized trials to assess CCB safety with respect to breast cancer risk.
Combination effects of gefitinib plus cisplatin in non-small cell lung cancer (NSCLC): Why have phase III trials failed?
Authors: C. Tsai, T. Chen, K. Chang, S. Hsiao
Journal: Journal of Clinical Oncology (2009)

11022 Background: Four phase III large scale randomized controlled trials combining standard chemotherapeutics and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced NSCLC have failed to show benefit. The mechanism for the failure is still yet not clear. Methods: Seventeen NSCLC cell lines were tested; two had induced P-glycoprotein (Pgp) over-expression. Three of the 4 EGFR mutants exhibited activating mutations. All lines were simultaneously treated with gefitinib plus cisplatin (GC). Selected 4 lines were tested with paclitaxel plus cisplatin (PC) or gefitinib (PG) and three-drug combination (PCG). The MTT assay with application of classical isobole method and statistical analysis was used and dose-log response curves (DRCs) were examined for evaluating the possible resistance mechanisms. Results: We found that combined GC regimen had significant antagonism at the IC50 level (13/15 lines; mean CI=1.184±0.037, P=0.001). The mean CI values of PCG were higher than or comparable with those of PC or PG in either EGFR wild type or mutant cells. DRC analysis mainly showed non-saturable passive resistance, suggesting that gefitinib 0.001–0.3 μM could interfere with cisplatin cell entry in a dose dependent fashion when cisplatin concentrations over 1–3μM, thus leaded to antagonism. Giving gefitinib 24 hours after administration of cisplatin could abolish the antagonism. Conclusions: In NSCLC cells, combination of GC showed antagonistic interaction likely because gefitinib interfered with cisplatin cell entry. Three-drug combination PCG was not better than two-drug combination PC or PG in either EGFR wild type or mutant cells. Clinically, simultaneously combined EGFR TKI with platinum in NSCLC should be avoided regardless of EGFR mutation status. [Table: see text]
Authors' response
Authors: C. Thienpont, S. Vermeire, P. Rutgeerts, G. Van Assche
Journal: Gut (2011)

We appreciate the letter sent by Drs Ustundag and Tezel1 as a reaction to our paper on the safety and efficacy of endoscopic balloon dilatation in patients with Crohn's disease.2 We would like to reply to some of the considerations raised by these authors.

First, we confirm that as far as anastomotic ileocolonic strictures is concerned endoscopic lesions suggestive of active disease do not predict worse efficacy or an increased complication rate. As outlined …