tbuckley/cabot-search huggingface dataset:
Cilengitide with cetuximab, cisplatin, and 5-FU in recurrent and/or metastatic squamous cell cancer of the head and neck: The ADVANTAGE phase II trial.
Authors: Jan Baptist Vermorken, Frederic Peyrade, Juergen Krauss, Ricard Mesia, Eva Remenar, Thomas C. Gauler, Ulrich Keilholz, Jean-Pierre Delord, Philippe Schafhausen, Jozsef Erfán, Tim H. Brummendorf, Lara Iglesias, Ullrich Bethe, Guillaume de La Bourdonnaye, Paul M. Clement
Journal: Journal of Clinical Oncology (2012)

5516^ Background: Prognosis for patients with recurrent and/or metastatic squamous cell cancer of the head and neck (R/M-SCCHN) is very poor. αvβ5 integrin is overexpressed in SCCHN and selective integrin blockade is being investigated as a treatment strategy. Methods: ADVANTAGE was a phase I/II study evaluating cilengitide with cetuximab and platinum-based chemotherapy. Eligible patients were ≥18 years with ≥1 measurable lesion, Karnofski performance status ≥70%, and confirmed R/M-SCCHN. The phase II part reported herein was an open-label, randomized, controlled trial investigating progression-free survival (PFS) in patients treated with 2 cilengitide 2000 mg regimens: once weekly (CIL1W) and twice weekly (CIL2W) administration combined with cisplatin, 5-FU, and cetuximab (PFE) as compared with PFE alone (control). Secondary objectives included overall survival (OS) and objective response (OR). Treatment-emergent adverse events (TEAEs) were monitored. Results: 184 eligible patients were enrolled. Overall, patient characteristics were similar across arms. Median duration of treatments was shorter in the CIL2W arm compared with the CIL1W arm (cilengitide: 16.1 vs 23.4 wk, cetuximab: 16.0 vs 22.6 wk, platinum: 16.0 vs 18.0 wk, and 5-FU: 14.6 vs 18.0 wk). Median PFS was 6.4 months in the CIL1W group, 5.6 months in the CIL2W group and 5.7 months in the control group, with CIL1W and CIL2W having HRs of 1.03 (95% CI: 0.67–1.59) and 1.55 (95% CI: 0.99–2.43) vs control. The latter HR was possibly due to less compliance in the CIL2W arm. Median OS was 12.4, 10.6, and 11.6 months in the CIL1W, CIL2W, and control groups, respectively. ORs were observed in 46.8%, 26.7%, and 35.5% of patients in the CIL1W, CIL2W, and control arms, respectively. Most common (≥15%) grade 3/4 TEAEs were neutropenia, hypokalemia, leukopenia, stomatitis, and fatigue. No safety differences were noted between treatment arms. Overall, there were 7 drug-related TEAEs (2 in CIL1W, 2 in CIL2W, and 3 in control) leading to death. Conclusions: In this population, neither of the cilengitide-containing regimens was able to demonstrate a PFS benefit over PFE alone.
An open-label, exploratory, limited dose escalation study to evaluate the pharmacokinetics, safety and tolerability of gemcitabine hydrochloride oral formulation in subjects with malignant tumors.
Authors: Nashat Y. Gabrail, Sharad A. Ghamande, Michael H. Silverman3, Carrie L. Smith, Hsiang-Ling Ho, Chia-Tsung Huang, Shu-Ping Hsueh, Chia-Li Lin
Journal: Journal of Clinical Oncology (2015)

e13537 Background: This open-label, phase 0, dose-escalation study of 3 successive cohorts was conducted to determine and characterize the plasma PK of D07001-F4, an oral formulation of gemcitabine HCl, in subjects with malignant tumors. Oral tolerability and safety were also assessed. Methods: Patients aged ≧18 yrs with PS 0–2 were eligible. D07001-F4 doses of either 2, 5, or 10 mg PO were administered once on Day 1 with 7 days of safety follow-up. Plasma and peripheral blood mononuclear cell (PBMC) samples were obtained for analysis of concentrations of, respectively, gemcitabine (dFdC) and 2’,2’-difluorodeoxyuridine (dFdU); and gemcitabine triphosphate (dFdCTP). Results: 3 subjects each (median 65 years [range 45 - 74]) were assigned to 3 dose escalation cohorts (2, 5, 10 mg). The PK parameter of Cmax was determined for dFdC and dFdCTP; Cmaxand AUC were found to be dose proportional, and the half-life was greater than 100 hours for dFdU. 24 adverse events were reported for 7 out of 9 subjects (78%). Only one G3 AE of worsening anemia was reported in Cohort 3, others are G1-2. Six hematologic events were experienced in three subjects. The most commonly reported events (i.e. those reported by more than one subject) were anemia, diarrhea, vomiting, and fatigue, which were each reported for 2 subjects. No deaths or Serious Adverse Events or drug-related AEs reported. Conclusions: Based on the complete absence of drug-related AEs with safety results, it is concluded that single dose of D07001-F4 is safe and well-tolerated at the doses used in this study and another Phase I study for MTD determination is ongoing. This study is funded by InnoPharmax Inc. (Clinical trial registration No.: NCT01678690) Clinical trial information: NCT01678690.PK variables of dFdC and dFdU in plasma and dFdCTP in PBMC. Dose levels (mg) 2 5 10 n of evaluable patients 3 3 3 dFdC Cmax (ng/mL) 2.9 (0.9-4.9) 3.0 (2.7-3.1) 1.5 (0.4-3.6) dFdU Cmax (ng/mL) 58 (45-76) 145 (75-219) 1,102 (133-2,823) AUC0-t (h*ng/mL) 4,060 (3,043-5,599) 8,991 (5,181-15,145) 69,878 (9,296-181,735) T1/2 (hr) 234 (196-253) 134 (112-151) 145 (103-217) dFdCTP Cmax (ng/mg protein) - 1.05 (0.6-1.5) 2.9
Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double‐Blind, Placebo‐Controlled Trials
Authors: Megan E. B. Clowse, Daniel J. Wallace, Richard A. Furie, Michelle A. Petri, Marilyn C. Pike, Piotr Leszczyński, C. Michael Neuwelt, Kathryn Hobbs, Mauro Keiserman, Liliana Duca, Kenneth C. Kalunian, Catrinel Galateanu, Sabine Bongardt, Christian Stach, Carolyn Beaudot, Brian Kilgallen, Caroline Gordon
Journal: Arthritis & Rheumatology (2016)

Objective Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double‐blind, placebo‐controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). Methods Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti–double‐stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI‐2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG‐2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5–60 mg/day). BILAG‐2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12‐week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG‐based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG‐2004 score, no worsening in the BILAG‐2004 score, SLEDAI‐2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders. Results In the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified. Conclusion In patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.
Scanxiety and quality of life among breast cancer survivors.
Authors: Juhee Cho, Danbee Kang, Soojung Park, Jeong Eon Lee, Seok Jin Nam, Hak Min Lee, Banseok Yang, Joon Jeong
Journal: Journal of Clinical Oncology (2015)

e20569 Background: Although follow-up exam after completion of rigorous treatment including surgery or chemotherapy would be considered as an easy, uncomplicated part of the cancer treatment process, the anxiety surrounding having scans ‘scanxiety’ often overwhelmed for many cancer survivors resulting in poor quality of lie. We assessed scanxiety among breast cancer survivors and find associated factors and its impact on quality of life. Methods: We conducted a cross-sectional survey of 891 breast cancer survivors at two cancer hospitals in Seoul, Korea from August 2013 to Jan 2014. Subjects were eligible if they were diagnosed stage 0 to III breast cancer at least 1 year ago, and had at least one time surveillance scan after completing treatment. We assessed scanxiety using SCale for ANxiety due to Surveillance Scan (SCANSS) which measures 1) anxiety related to scan; 2) discomfort due to scan; and 3) needs for surveillance scan. Survivors’ anxiety and depression (HADS) and quality of life (WHOQOL-BRF) were also measured along with socio-demographic and clinical information. Descriptive statistics and multi-variable linear regression was conducted using STATA 12.1. Results: Mean age of the participants was 51.9(±9.5), and 14.4% was DCIS, and mean time since diagnosis was 3.74 years (±3.0).Of total 94.6% of the participants thought surveillance scan is necessary. However, 45% expressed there are too many tests with the surveillance. About 65% reported that daily activity is disturbed due to anxiety caused by surveillance exam. 57.2% said it hinders their work-ability and concentration. Younger and patients in a long-distance had higher needs for surveillance scan. Divorced or separated, younger, and patients with stronger therapy reported higher anxiety associated with scan. Patient who had more surveillance tests experience higher anxiety adjusting age, stage, treatment, and years of survivorship (p < 0.01) resulting in poor quality of life (p < 0.01). Conclusions: While most patients agreed with the necessity of surveillance scan, they experienced unfamiliarity, discomfort, anxiety, and distress due to the procedure as well as fear of recurrence. Health professionals need to find ways to prevent this emotional distress and help patients to cope with it.
Immunomodulatory Effects of Vitamin D: Implications for the Prevention and Treatment of Graft Versus Host Disease
Authors: Jacalyn Rosenblatt, Adam Bissonnette, Zekui Wu, Baldev Vasir, Corrine Zarwan, Whitney Keefe, Robin Joyce, James D. Levine, Brett Glotzbecker, Nataliya Rozenvayn, Dimitrios Tzachanis, Vassiliki Boussiotis, Donald Kufe, David Avigan
Journal: Blood (2008)
Ten-year follow up of patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with 400 mg or 800 mg of imatinib daily.
Authors: Koji Sasaki, Hagop M. Kantarjian, Preetesh Jain, Elias Jabbour, Naveen Pemmaraju, William G. Wierda, Alessandra Ferrajoli, Sara Dellasala, Sherry Pierce, Srdan Verstovsek, Farhad Ravandi, Susan Mary O'Brien, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2014)

7024 Background: The tyrosine kinase inhibitor imatinib is standard therapy for patients with chronic myeloid leukemia in chronic phase (CML-CP). It has been suggested that higher-dose imatinib (HD-IM) may offer faster and deeper responses. The purpose of this study was to assess long-term follow-up data of patients treated with HD-IM (minimum follow-up 8 years). Methods: Patients with newly diagnosed CML-CP received daily imatinib 400 mg (IM400; 70 patients) or 800 mg (IM800; 201 patients) in consecutive clinical trials. Patients were assessed for cytogenetic and molecular response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS). Results: The 271 patients’ median follow-up time was 118 months. The median age was 48.3 years (range, 15.1-84.8 years). Sokal risk scores, rates of best response, FFS, TFS, EFS, and OS are given in Table 1. The response rates at 3, 6, and 12 months in IM800 patients were significantly higher than those of the IM400 patients. The overall MMR4.5 and MMR rates of the IM800 patients were significantly higher than those of the IM400 patients. The IM800 patients also had significantly higher 10-y EFS and 10-y TFS, with small, non-significant trends for 10-y OS and 10-y FFS. Conclusions: IM800 patients tended to have better response rates than IM400 patients, particularly for MR4.5. This translates into better EFS but not OS. Patient characteristics and outcomes. IM400 [n= 70], % IM800 [n= 201], % P value Sokal risk 0.239 Low 69 63 Intermediate 29 28 High 3 9 Response at 3M CCyR 30 56 <0.001 MCyR 71 89 0.001 Response at 6M CCyR 39 77 <0.001 MCyR 79 90 0.020 Response at 12M CMR 3 11 0.033 MR4.5 17 30 0.038 MMR 36 72 <0.001 CCyR 60 80 0.001 Best (cumulative) response CMR 47 57 0.166 MR4.5 56 74 0.005 MMR 74 86 0.032 CCyR 84 90 0.191 10-y outcome FFS 50 55 0.378 TFS 83 91 0.051 EFS 66 77 0.041 OS 80 84 0.590
Expression of toll-like receptors in seven malignant tumors.
Authors: Priscila I. Valdiviezo, Claudio J Flores, Luis Mas, Alfredo Aguilar, Silvia P Neciosup, Joseph A. Pinto, Mayer Zaharia, Henry Gomez, Carlos S. Vallejos
Journal: Journal of Clinical Oncology (2014)

e22088 Background: Toll-like receptor role in tumor pathogenesis has been largely proven. Our purpose was to determine the differences of TLRs (TLR1 - TLR10) expression in 7 types of malignant tumors: gastric, lung, ovarian and breast cancer, acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Methods: We retrieved normalized expression data from public databases (GSE29272, GSE1800, GSE49032, GSE37642, GSE30311, GSE22820, GSE19234, GSE22820) profiled with different microarray platforms. Expression levels were normalized to geometric median of 11 housekeeper genes (C1orf43, CHMP2A, C15orf24, GPI, PSMB2, PSMB4, RAB7A, REEP5 SNRPD3, VCP, VPS29). Expression medians were compared to each tumor type and variation coefficients (VC) were estimated. Results: We analyzed 1003 cases (ALL 108; AML 140; BC 186; gastric 268; lung 49; ovary 98, prostate 154). Lowest TLRs expression was observed in ALL while highest expression occurred in breast cancer. Overall, gastric cancer had the lowest TLR variation and the highest variation was observed in breast cancer. TLR1, TLR3, TLR4 and TLR5 did not present differences between lung, ovarian and prostate cancer (Table). Conclusions: TLRs are differentially expressed across several tumor types. Highest expression and variation was observed in breast cancer, maybe explained by molecular subtypes. These receptors are targetable and its involvement in tumor biology should be evaluated. ALL AML Breast Gastric Lung Ovarian Prostate Median CV Median CV Median CV Median CV Median CV Median CV Median CV TLR1 0.73 28.5 0.77 11.77 1.01 64.01 0.52 7.57 0.8 14.27 0.65 12.96 0.65 13.44 TLR2 0.69 11.89 0.94 8.99 1.02 59.51 0.76 6.79 0.94 12.14 0.69 12.16 0.63 11.26 TLR3 0.3 18.04 0.44 9.96 0.98 64.07 0.65 9.07 0.75 15.26 0.75 11.43 0.75 9.7 TLR4 0.29 14.08 0.74 17.95 0.97 57.63 0.58 8.66 0.79 12.77 0.71 15.03 0.72 9.18 TLR5 0.43 10.71 0.62 10 1 71.48 0.76 5.45 0.73 12.29 0.73 10.22 0.69 6.9 TLR6 0.45 12.29 0.61 7.67 1 69.57 0.61 6.23 0.49 9.56 0.57 12.88 0.42 9.27 TLR7 0.34 34.22 0.45 14.52 0.49 159.04 0.51 8.85 0.72 13.49 0.57 14.01 0.53 8.7 TLR8 0.36 14.47 0.66 22.28 0.67 100.83 0.61 5.01 0.7 12.86 0.52 13.87 0.43 13.58 TLR9 0.48 12.71 0.62 5.27 0.97 94.05 0.8 3.73 0.49 6 0.72 6.67 0.46 8.53 TLR10 0.45 17.85 0.51 6.09 0.59 97.33 0.38 11.37 0.44 10.04 0.4 15.67
BRIM8: A phase III, randomized, double-blind, placebo-controlled study of vemurafenib adjuvant therapy in patients with surgically resected, cutaneous BRAF-mutant melanoma at high risk for recurrence (NCT01667419).
Authors: Karl D. Lewis, Michele Maio, Mario Mandalà, Betty J Nelson, Grant R. Goodman, Dirk Schadendorf
Journal: Journal of Clinical Oncology (2014)

TPS9118^ Background: Approximately 50% of melanomas carry a mutation in the BRAF gene. The oral BRAF inhibitor vemurafenib (VEM) has demonstrated meaningful clinical benefit in BRAFV600 mutation-positive, locally advanced/unresectable or metastatic melanoma. For patients (pts) with resected melanoma, interferon alfa-2b represents the only widely approved adjuvant therapy; however, its use is limited by a modest improvement in disease recurrence and a high incidence of severe adverse effects that lead to treatment discontinuation in up to a third of pts. BRIM8 is a phase III, international, multicenter, double-blind, randomized, placebo-controlled study designed to evaluate the safety and efficacy of VEM in pts with resected cutaneous melanoma at high risk (>50%) for recurrence (stage IIC and III disease). Methods: Pts aged ≥18 yrs with histologically confirmed stage IIC or III BRAFV600mutation-positive (by cobas testing) melanoma of cutaneous origin that has been completely resected are eligible. Pts without clinical or radiologic evidence of regional lymph node involvement must undergo sentinel lymph node biopsy, and those with evidence of regional or sentinel lymph node involvement must undergo complete regional lymphadenectomy. Pts with a history of systemic therapy for treatment or prevention of melanoma (including interferon alfa-2b) are ineligible. Two cohorts (C) will enroll ~ 725 pts: C1—500 pts with completely resected stage IIC, IIIA (one or more nodal metastasis >1 mm in diameter, per Rotterdam classification), or IIIB cutaneous melanoma; C2—225 pts with stage IIIC cutaneous melanoma. Pts will be randomized 1:1 to receive VEM (960 mg bid) or placebo for 52 weeks with randomization stratified by pathologic stage and region (C1) and by region (C2). Primary efficacy outcome measure is investigator-assessed disease-free survival. Secondary efficacy outcome measures include overall and distant metastasis-free survival. Safety, pharmacokinetic, and pt-reported outcomes will also be assessed. As of 13 Jan 2014, 179/196 sites are active and 154 pts have been randomized (C1: 89; C2: 65). Clinical trial information: NCT01667419.
Adverse Effects of Statins
Authors: Stephen J. Malachowski, Alexander M. Quattlebaum, Branko Miladinovic
Journal: JAMA (2017)

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Characterization of colorectal cancer (CRC) in Lynch syndrome (LS) patients with <i>MSH6</i> or <i>PMS2</i> mutations.
Authors: Jean Kyung Lee, Jinru Shia, Rohini Rau-Murthy, Marina Corines, Erin E. Salo-Mullen, Arnold Markowitz, Mark E. Robson, Kenneth Offit, Jose G. Guillem, Leonard Saltz, Zsofia Kinga Stadler
Journal: Journal of Clinical Oncology (2013)

1555 Background: The majority of LS patients harbor germline mutations in the MLH1 or MSH2 genes. However, ~10% have MSH6 and ~&lt;5% PMS2 mutations. An attenuated form of LS has been suggested in MSH6/PMS2 carriers with decreased CRC risk and older age of disease onset. As recent guidelines suggest that initiation of CRC screening may be delayed in such patients, we characterized our patients with MSH6/PMS2-associated CRC. Methods: We obtained an IRB waiver to identify all LS patients with CRC, defined as the presence of a deleterious germline mutation in a MMR gene, from the Clinical Genetics database at MSKCC. Clinical, pathologic, and genetic features were extracted from medical records and Progeny software. Results: Of 147 LS patients with CRC, 23 had mutations in the MSH6 (n=16, 11%) or PMS2 (n=7, 5%) genes. Mean age at CRC diagnosis was 48.5 yrs (range 32-70) in MSH6 and 40.7 (range 22-57) in PMS2 carriers. 16 (70%) and 5 (22%) were diagnosed at age ≤50 or ≤35, respectively. 4 (17%) had metachronous and 3 (13%) synchronous primary CRCs, and 5 (22%) had additional LS-associated cancer. Although all 23 LS patients met Revised Bethesda guidelines, only 50% of MSH6 and 0 of the PMS2 carriers met Amsterdam I/II criteria (AC). Of 32 independent primary CRCs, 18 (56%) were stage I/II, 9 (28%) stage III, and 1 (3%) stage IV. 9/9 MSH6 and 4/4 PMS2 CRCs had high-frequency microsatellite instability. In MSH6 carriers, 11/13 had absence of MSH6protein expression only on IHC, 1 had inconclusive MSH6 staining, and 1 had absence of both MSH6 &amp; MSH2 proteins. In PMS2carriers, 7/7 had absence of PMS2 on IHC, 2 also had equivocal/focal MLH1 staining. Right-sided CRC was present in 50% and at least 40% had mucinous features. 26/29 (90%) of tumors underwent segmental resection. 6/11 stage II patients received adjuvant chemotherapy including 2 with pT4N0 tumors. With a mean follow-up of 5.6 yrs to date, 1 patient is known to have developed recurrent CRC. Conclusions: Although the majority of MSH6/PMS2 CRC patients do not meet AC, 70% of CRCs were diagnosed at age ≤50, 22% at age ≤35, and 30% had synchronous/metachronous CRCs. These findings have important implications for CRC surveillance and may not support delaying colonoscopy initiation in MSH6/PMS2 LS families.