tbuckley/cabot-search huggingface dataset:
The MIRACLE trial: A randomized, controlled trial comparing green tea extract versus placebo for the prevention of metachronous colon adenomas in a screening population.
Authors: Thomas Ettrich, Julia Stingl, Rainer Muche, Andreas Berger, Thomas Seufferlein
Journal: Journal of Clinical Oncology (2012)

TPS1612 Background: Prevention of colorectal cancer is a major health care issue. After polypectomy there is an increased risk of polyp recurrence and various means of chemoprevention have been tried to prevent this. NSAIDs have been shown to be effective but confer side effects such as gastrointestinal bleeding. Nutraceuticals such as polyphenols from tea plants have demonstrated remarkable therapeutic and preventive effects in molecular, epidemiological and some clinical trials. However, their value in preventing colorectal polyps has not been demonstrated in a large, randomized trial. The beneficial safety profile of decaffeinated green tea extract and accumulating evidence of its cancer preventive potential justify and require, in our view, a validation of this compound for the nutriprevention of colorectal adenoma. Good accessibility and low costs might render this neutraceutical a top candidate for wider use as nutritional supplement in colon cancer prevention. Methods: Randomized, double blinded, placebo-controlled, multicenter trial. After a one month run-in period with verum, 2534 patients (age: 50-80 years) who have undergone polypectomy within the last 6 months will be randomized to receive either decaffeinated green tea extract (containing 150 mg epigallocatechin gallate (EGCG) two times daily) or placebo over a period of three years. 2028 patients are expected to complete the whole study course. Primary outcome: Incidence of metachronous colorectal adenomas (tubulovillous, tubular, villous, serrated lesions) at the 3 year follow-up colonoscopy Secondary outcomes: Occurrences, number, localization, size and histological subtypes of adenomas, frequency of colorectal carcinoma. In addition, genetic and biochemical biomarkers in blood samples and genetic alterations (e.g. K-ras, B-raf, specific microRNAs) in tissue samples of adenomas will be analyzed (biobanking subprojects). Additionally, nutrikinetics and nutrigenetics of EGCG and other catechins will be assessed in healthy volunteers. Patient recruitment has started in November 2011. We expect the last patient out in fall 2017. (Trial identifier: NCT01360320)
Phase I/II trial of continuous hepatic arterial infusion (HAI) of Irinotecan in patients with hepatocellular carcinoma (HCC). Preliminary results
Authors: M. Pantaleo, E. Derenzini, F. Piscaglia, R. Golfieri, L. Bolondi, M. G. Mirarchi, R. Danesi, G. Biasco, G. Brandi
Journal: Journal of Clinical Oncology (2006)

14061 Background: No standard therapies are available for HCC patients (pts) who are not eligible for curative treatments (surgery, RF, TACE or PEI). Methods: This dose finding phase I/II study investigates the tolerability of increasing doses of continuous HAI of CPT-11 (during days 1–5 every 21) in pts with histologically confirmed Child A/B HCC, confined to the liver, not eligible for curative treatments. Secondary endpoints are pharmacokinetics and efficacy. To date, 5 dose levels (DL) of CPT-11 have been investigated (from 7,5 to 17,5 mg/m 2 /die) and the 6 th (20 mg/m 2 /die) being evaluated. An arterial port-a-cath was placed in the hepatic artery by percutaneous catheterization of the femoral or axillary artery. Before each cycle an angiography was performed to define the optimal liver perfusion. DLT was defined as one G4 hematogical and/or two G3 nonhematological toxicities or liver function impairment (Child C). AEs were graded using NCI-CTC. Responses were evaluated after the 3 rd cycle with ultrasonography or CT scan (WHO criteria). Results: To date 16 pts have been enrolled and evaluated for tolerability. Median age is 63, 8 years (range 41–80), M/F 11/5, median ECOG 1 (0–2), Child-Pugh A/B 10/6 . Total n° of courses was 41 (median 2, range 1–10). DLT was not reached. Two grade 3 toxicities were reported at DL 4: diarrhea in 1 pt and anemia in another pt. There were no G4 toxicities. Most common G1–2 toxicities at any DL were: neutropenia 5 pts (31%), nausea/vomiting 4 pts (25%), diarrhea 3 pts (18%), thrombocytopenia 2 pts (12.5%). In two pts (DL3 and DL4) treatment was discontinued because of chemotherapy induced arteritis after 1 and 3 courses respectively. 12 pts were assessable for response: 3 PR, 6 SD, 3 PD. α-fetoprotein levels decreased significantly in 6 pts (50%). Pharmacokinetics data will be presented later. Conclusions: To date MTD hasn’t been reached. At DL 1–5 this schedule shows little and manageable toxicity - without impairment of liver function - and promising activity (PR+SD=75%). No significant financial relationships to disclose.
Validation of Association of Hypertension at the CYP11B1/B2 Locus in Caucasians.
Authors: S. Alvarez-Madrazo, S. Padmanabhan, E. Friel, S. M. MacKenzie, M. J. Brown, M. J. Caulfield, P. B. Munroe, M. Farrall, J. Webster, N. J. Samani, A. F. Dominiczak, Olle Melander, E. Davies, J. M. Connell
Journal: Endocrine Reviews (2010)
Weekly paclitaxel (TAX) and capecitabine (CAP) for metastatic breast cancer (MBC) patients (PTS) previously treated with anthracycline-containing therapy: A phase I dose-finding study
Authors: S. Susnjar, S. Bosnjak, S. Radulovic, J. Stevanovic, M. Gajic-Dobrosavljevic, M. Kreacic
Journal: Journal of Clinical Oncology (2005)

851 Background: We sought to determine maximal tolerated dose (MTD), tolerability and preliminary activity of TAX plus CAP therapy in MBC pts previously treated with anthracycline based regimens. The protocol was designed during the Workshop on Methods in Clinical Cancer Research (Flims, 2000). Methods: Eligibility: Pts with histologically confirmed MBC, previously treated with anthracycline - containing therapy (adjuvant anthracycline chemotherapy or a maximum of one line of anthracycline chemotherapy for metastatic disease), were eligible for the inclusion into the study. Treatment: Fixed dose of CAP (1000 mg/m2 twice daily, D1 - D14) were combined with three dose levels of weekly administered TAX (D1, D8 and D15), starting from 60 mg/m2/wk and escalated by 15 mg/m2/wk. Results: Eleven patients with MBC were included in a single - center study and all of them were eligible for toxicity and response. Three pts were treated at dose level 1 (60 mg/m2 TAX), 6 received 75 mg/m2 and 2 received 90 mg/m2 of weekly TAX. Grade 3 nail toxicity accompanied with grade 3 hand/foot syndrome and/or grade 2 skin toxicity occurred in two patients receiving TAX of 75 mg/m2 weekly, and although not life-threatening, was determined to be severe enough to reach the criteria for DLT. Objective tumor responses were observed in 8 out of 11 patients: 1 CR and 7 PR’s. Conclusions: The recommended dose for phase II study was CAP 1000 mg/m2 twice daily for 14 days and TAX 60 mg/m2 weekly. TAX plus CAP appears to be a very active combination in anthracycline-pretreated patients with MBC, with manageable toxicity. Our results are comparable to those reported by Bari et. al (Proc ASCO 2003: 66, # 262). Furthermore, we have demonstrated that escalation of TAX dose to 75 mg/m2 and 90 mg/m2 is not feasible due to severe nail and skin toxicity. No significant financial relationships to disclose.
Indolent non follicular non-hodgkin lymphoma : prospective evalutation of gisl prognostic criteria for watch and wait policy in 109 patients
Authors: V. Cellea, F. Morabito, S. Luminari, C. Stelinato, A. Sirotti, M. Russo, K. Cagossi, M. Goldaniga, M. Federico, L. Baldini
Journal: Annals of Oncology (2005)
Arsenic trioxide as primary treatment in acute promyelocytic leukemia
Authors: S. A. Aziz
Journal: Journal of Clinical Oncology (2006)

16533 Acute Promyelocytic Leukemia (APL) is a separate, distinct and biologically unique subset of Acute Myelogenous Leukemia (AML). The affordability of ATRA is detrimental for its use especially in the developing world. The use of Arsenic trioxide (As2O 3 ) has radically changed the treatment, initially for relapsed APL and now is being used upfront as first line therapy in APL some studies. We accrued 11 cases (6 males, 5 females) of APL for the past 1 year. 2 patients of these had been already treated with ATRA + chemotherapy (Daunorubicin and Cytosine Arabanoside). These relapsed patients were switched over to Arsenic trioxide. One of these relapsed patients has completed the treatment and is in CR for the past 6 months after completing treatment. The other patient has recently completed the treatment and is in remission. 9 of our patients are newly diagnosed and could not afford ATRA and chemotherapy. All these patients were explained the treatment protocol and after obtaining a formal consent, patients were put on Arsenic trioxide. The protocol consists of Induction therapy with Arsenic trioxide given in a dose of 0.15 mg/kg/day till CR is achieved or to a maximum of 60 doses, followed by Consolidation treatment with Arsenic trioxide in the similar dose schedule but only for 28 days, and finally Maintenance therapy with Arsenic trioxide every 10 days a month for a total of 6 months with an interval of 4–6 weeks in between the cycles. Of the remaining patients (n = 7), 2 patients did not respond to Arsenic trioxide after 60 doses. The remaining patients (n = 5) are in different phases of treatment (all having completed Induction therapy) and are presently in CR (Mean duration to avhieve CR-57 days, documented by bone marrow examination). There were no major morbidities and none of our patients exhibited APL syndrome. The lower cost of treatment with Arsenic trioxide (Approx. Rs. 50–60,000) compared to ATRA + chemotherapy (Approx. Rs. 90,000–1,10,000), the magnitude of response and the least encountered adverse effects seem awesome in this treatment especially in the developing countries. No significant financial relationships to disclose.
Combined Treatment with Epigenetic, Differentiating, and Chemotherapeutic Agents Cooperatively Targets Tumor-Initiating Cells in Triple-Negative Breast Cancer
Authors: Vanessa F. Merino, Nguyen Nguyen, Kideok Jin, Helen Sadik, Soonweng Cho, Preethi Korangath, Liangfeng Han, Yolanda M.N. Foster, Xian C. Zhou, Zhe Zhang, Roisin M. Connolly, Vered Stearns, Syed Z. Ali, Christina Adams, Qian Chen, Duojia Pan, David L. Huso, Peter Ordentlich, Angela Brodie, Saraswati Sukumar
Journal: Cancer Research (2016)

Efforts to induce the differentiation of cancer stem cells through treatment with all-trans retinoic acid (ATRA) have yielded limited success, partially due to the epigenetic silencing of the retinoic acid receptor (RAR)-β The histone deacetylase inhibitor entinostat is emerging as a promising antitumor agent when added to the standard-of-care treatment for breast cancer. However, the combination of epigenetic, cellular differentiation, and chemotherapeutic approaches against triple-negative breast cancer (TNBC) has not been investigated. In this study, we found that combined treatment of TNBC xenografts with entinostat, ATRA, and doxorubicin (EAD) resulted in significant tumor regression and restoration of epigenetically silenced RAR-β expression. Entinostat and doxorubicin treatment inhibited topoisomerase II-β (TopoII-β) and relieved TopoII-β-mediated transcriptional silencing of RAR-β Notably, EAD was the most effective combination in inducing differentiation of breast tumor-initiating cells in vivo Furthermore, gene expression analysis revealed that the epithelium-specific ETS transcription factor-1 (ESE-1 or ELF3), known to regulate proliferation and differentiation, enhanced cell differentiation in response to EAD triple therapy. Finally, we demonstrate that patient-derived metastatic cells also responded to treatment with EAD. Collectively, our findings strongly suggest that entinostat potentiates doxorubicin-mediated cytotoxicity and retinoid-driven differentiation to achieve significant tumor regression in TNBC. Cancer Res; 76(7); 2013-24. ©2016 AACR.
Circadian patterning of continuous floxuridine infusion reduces toxicity and allows higher dose intensity in patients with widespread cancer.
Authors: R von Roemeling, W J Hrushesky
Journal: Journal of Clinical Oncology (1989)

Continuous long-term 5-fluoro-2'-deoxyuridine (floxuridine; FUDR) infusion frequently causes severe and dose-limiting gastrointestinal toxicity when administered at a constant rate at commonly prescribed dose levels. In preclinical studies, a circadian infusion pattern peaking late in the daily activity phase was better tolerated and had superior antitumor activity than a constant infusion against a transplanted tumor. Based upon these data and upon other chronobiological cytokinetic and pharmacologic considerations, we compared a circadian patterned variable rate infusion with a maximal flow rate in the late afternoon/early evening and minimum flow rate during the early morning hours to a constant rate infusion in 54 patients with widespread cancer. All FUDR infusions were administered using an implanted drug pump. In a pilot crossover study and a second randomized trial, patients with metastatic malignancies treated with equal dose intensities experienced less frequent and less severe diarrhea, nausea, and vomiting following variable rate infusion. In a third study, the dose intensity of variable rate infusion was escalated stepwise to determine the maximum-tolerated dose. Patients receiving time-modified FUDR infusion tolerated an average of 1.45-fold more drug per unit time while evincing minimal toxicity. FUDR infusion was found to have activity against progressive metastatic renal cell cancer (RCC). Increased dose intensity achieved by optimal circadian shaping may improve the therapeutic index of infusional FUDR and may help control malignancies that are refractory to conventional chemotherapy.
Abstract 14455: Glucose Variability Determined by Continuous Glucose Monitoring System Is More Associated with Poor Clinical Characteristics in ST-Segment Elevation Myocardial Infarction Patients with Type 2 Diabetes Mellitus and Impaired Glucose Tolerance, in Comparison with Hemoglobin A1c Levels
Authors: Kozo Okada, Masaomi Gobara, Noriaki Iwahashi, Zenko Nagashima, Hiroyuki Suzuki, Keiko Takano, Eiichi Akiyama, Yasushi Matsuzawa, Masaaki Konishi, Kenichiro Saka, Nobuhiko Maejima, Mitsuaki Endo, Kengo Tsukahara, Yoshio Tahara, Kiyoshi Hibi, Masami Kosuge, Toshiaki Eniba, Kazuo Kimura
Journal: Circulation (2012)

Background: Glucose variability may play an important role in development of atherosclerosis. The objective of this study was to assess the relationship of glycemic variability determined by a cont...
Use of monthly oral ibandronate to prevent anastrozole-induced bone loss during adjuvant treatment for breast cancer: Two-year results from the ARIBON study
Authors: J. Lester, D. Dodwell, O. P. Purohit, S. A. Gutcher, S. P. Ellis, R. Thorpe, J. M. Horsman, J. E. Brown, R. A. Hannon, R. E. Coleman
Journal: Journal of Clinical Oncology (2008)

554 Background: The ARIBON trial is a double-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in postmenopausal women taking adjuvant anastrozole for their endocrine responsive breast cancer. Methods: BMD was assessed in 131 patients prior to commencing adjuvant endocrine treatment. 68, 50, and 13 patients were found to be normal (T >-1.0, group 1), osteopenic (T -1.0 to -2.5, group 2), and osteoporotic (T <-2.5, group 3), respectively. All patients were treated with anastrozole 1mg once a day and calcium and vitamin D supplementation. In addition, group 2 patients were randomized on a 1:1 basis to receive either treatment with oral ibandronate 150 mg every month or placebo. Group 3 patients were treated with open label oral ibandronate 150mg every month. BMD and bone marker measurements were repeated at regular intervals for two years. Group 1 patients were followed up on calcium and vitamin D supplements alone. Results: BMD changes in groups 2 and 3 are shown in the table. In group 2 the mean difference in percentage BMD changes between the ibandronate and placebo treated patients after 1 and 2 years was 5.5 and 6.2% (95% CI 2.4–10.0) at the lumbar spine (LS) and 3.2 and 4.5% (95% CI 1.7–7.3) at the hip (TH) (p<0.01, independent samples t test). After 1-year Urinary n-telopeptide (uNTX), serum c-telopeptide (sCTX), and serum bone-specific alkaline phosphatase (sBALP) levels declined in patients receiving ibandronate (21, 26, and 23%, respectively) and increased in those taking placebo (40, 35, and 40%, respectively). Biomarker assessments at 2 years are ongoing. As expected, group 1 patients lost 4.8% (range -13.8, +4.5) at the LS and 3.7% (range -15.9, +1.3) at the TH after 2 years. Conclusions: Ibandronate 150 mg by mouth once a month prevents anastrozole-induced bone loss and results in significant increases in BMD at the LS and TH in osteopenic and osteoporotic patients. Mean Percentage Change in BMD (Ranges) Osteopenia Osteoporosis Ibandronate Placebo Ibandronate 1 yr n=23 2 yr n=21 1 yr n=25 2 yr n=19 1 yr n=12 2 yr n=12 LS +3.11 (-3.8, +15.1) +2.98 (-8.9, +19.9) -2.35 (-10.5, +2.2) -3.22 (-16.0, +4.3) +5.02 (-8.7, +15.2) +3.52 (-4.9, +14.6) TH +0.98 (-4.1, +5.6) +0.60 (-9.0, +6.9) -2.27 (-9.9, +5.2) -3.90 (-12.3, +7.2) +2.90 (-1.0, +8.5) +2.49 (-3.7, +8.1) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology, Roche AstraZeneca Oncology
Utility of in vitro chemosensitivity testing of primary and metastatic hepatobiliary neoplasms
Authors: A. D. Tevar, T. Thambi-Pillai, M. Thomas, S. M. Rudich, J. F. Buell
Journal: Journal of Clinical Oncology (2005)

4256 Background: A majority of patients with primary or metastatic tumors to the liver experience minimal benefit with standard chemotherapy and are exposed to considerable toxicity. The purpose of this review was to identify specific tumor cell responses to chemotherapeutic agents effective in common hepatobiliary malignancies. This information may allow tailoring drug therapies to specific patient tumor cells, thus enhancing clinical outcomes. Methodology: Tumors were submitted to Precision Therapeutics for in vitro assessment of chemoresponsiveness using the ChemFx assay. Serial concentrations of each drug were used and a percentage of cell kill was then calculated for each drug concentration. Patients with hepatobiliary malignancies at a tertiary referral center were analyzed. Results: Over a 28 months 29 patients with primary hepatobiliary and metastatic lesions were reviewed. The most common lesion was metastatic colon adenocarcinoma (n=13, 44.8%), followed by cholangiocarcinomas (n=4, 13.8%), hepatocellular carcinoma (n=3, 10.3%) and primary gallbladder adenocarcinomas (n=2, 6.9%). Other metastatic lesions tested included: stomach adenocarcinoma, ovarian serous carcinoma, ovarian adenocarcinoma, renal cell carcinoma, esophageal adenocarcinoma, pancreatic adenocarcinoma and pancreatic islet cell. In the patients with metastatic colon adenocarcinoma to the liver, agents with high in vitro cell kill rate included: cisplatin (n=9, 69.2%), fluorouracil (n=8, 61.5%), doxorubicin (n=5, 38.5%), oxaliplatin (n=5, 38.5%) and combination leucovorin+fluorouracil+oxaliplatin (n=3, 23.1%). In 3 patients, no agents expressed high tumor cell kill rates. In the cholangiocarcinoma group, high tumor kill rates included: cisplatin (n=3, 75%) and paclitaxel (n=3, 75%). For hepatocellular carcinoma patients, cisplatin, fluorouracil, mitomycin and vinblastine (all n=2, 66%) were highly effective agents. Conclusions: We found that in vitro chemosensitivity assays could yield specific data for agents effective in hepatobiliary lesions. A well designed trial to determine accuracy is indicated to define improved clinical outcomes with tumor cell specific therapy in hepatobiliary malignancies. No significant financial relationships to disclose.
Continuous androgen deprivation in stage C and D prostate cancer: Could the treatment be suspended?
Authors: B. Castagneto, V. Ferraris, M. Perachino, M. Clerico
Journal: Journal of Clinical Oncology (2004)

4745 Purpose To evaluate whether patients (pts) with advanced prostate cancer (APC), programmed for continuous androgen deprivation (CAD), could suspend the treatment when stable clinical and biological response (BCR) has been achieved since at least 30 months. Methods BCR was defined as follows: PSA value not exceeding 0.5 ng/ml, normal findings on prostate digital rectal examination (DRE), no dysuria. Following informed consent we proposed suspension CAD to pts in BCR for at least 30 months, in alternative to prolong the treatment until disease progression. Reintroduction of androgen deprivation was planned in case of: PSA value exceeding 10 ng/ml, positive prostate DRE, symptoms of disease. Results out of 184 consecutive pts with APC, 49 pts in BCR were identified and 46 accepted the proposal of suspending CAD. Median age 78 (range 60 to 91); 15 (31%) stage C, 7 (15%) stage D1, 24 (53%) stage D2. The median duration of treatment before suspension has been 36.8 months (range 28.5 to 78.6) (CI 95% 36 to 40.4). After a median follow-up of 34.7 months (range 5.5 to 80.6) (CI 95% 28.3 to 52.5) we registered 8 (17.3%) pts in disease progression, but, out of the 12 (26%) deaths recorded, only 4 (8.6%) occurred among pts with progressive disease. In 28 (60.8%) pts androgen deprivation has been restarted. The estimated median time to treatment reintroduction according to Kaplan Meier method is 26 months. In 9 (19.5%) pts the plasma level of testosterone did not exceed 0.50 ng/ml, indicating the absence of gonadal function recovery. The pharmaceutical saving from suspending the treatment has been 711819.18 dollars. Conclusions Based on clinical outcome of our series we conclude that the suspension of CAD could be a suitable strategy in pts in BCR since at least 30 months. Nevertheless further studies have to be done in order to confirm our results. Furthermore could be interesting underline the potential saving from therapy suspension in this set of pts. No significant financial relationships to disclose.