tbuckley/cabot-search huggingface dataset:
Psychosocial barriers to clinical trial participation as perceived by oncologists and patients
Authors: N. J. Meropol, J. S. Buzaglo, J. L. Millard, C. G. Ridgway, N. Damjanov, S. M. Miller, E. A. Ross, J. D. Sprandio, P. Watts
Journal: Journal of Clinical Oncology (2005)

6008 Background: Little is known about psychosocial influences on clinical trial (CT) participation by oncologists (oncs) and patients (pts). Methods: A survey was distributed to all 478 medical oncologists in Pennsylvania and a subset of their patients. In addition to demographic characteristics, information on practical and psychosocial barriers to clinical trial participation was evaluated using 5-point Likert scales, and relative ranking. Results: Surveys were completed by 136 oncs (81% men; median age 49 [range 32–71]; 61% non-academic; 14% non-white) and 159 pts (47% men; median age 55 [range 22–85]; 11% non-white; 57% educated beyond high school). 84% of pts heard of CTs; higher education (p<0.0001, Fisher’s Exact) and white race (p<0.0001) were associated with awareness. 98% of oncs and 85% of pts strongly agreed that CTs are important to improving cancer treatment. 79% of oncs strongly agreed that pts benefit from participating, but only 57% of pts felt strongly that they would benefit (p<0.0001, Fisher’s Exact). When ranking 7 potential patient barriers to CTs (2 practical and 5 psychosocial), pts identified fear of side effects as the greatest barrier. In contrast, oncs ranked this last among psychosocial barriers (p<0.0001, Wilcoxon). Compared to those in academic centers, oncs from non-academic settings ranked fear of side effects as a less important barrier (p=0.01, Wilcoxon). Other non-practical barriers with significant discordance were: lack of trust in medical establishment (oncs rank 2, pts rank 6, p<0.0001), and patients’ lack of understanding of clinical trials (oncs rank 4, pts rank 7, p<0.0001). Oncs (rank 1) and pts (rank 2) ranked random assignment highly, with non-white oncs ranking this as less important than whites (p=0.004). Male pts ranked fear of placebos less than females (p=0.004). Conclusions: Oncologists and patients are aware of CTs and have favorable attitudes toward them. However, there is significant discordance in perceptions of psychosocial barriers to participation. Oncs may underestimate the impact of pt fears about side effects on CT participation. Improved understanding of oncologist and patient perceived barriers can help overcome low participation rates in CTs. No significant financial relationships to disclose.
A phase I/II study of the safety and anti-cancer activity of IV-administered belinostat (PXD101) plus carboplatin (C) or paclitaxel (P), or both in patients with advanced solid tumors
Authors: R. Sinha, R. Moliffe, M. Scurr, L. Vidal, S. A. Engelholm, P. Buhl Jensen, A. Normann, S. Li, J. De Bono, U. Lassen
Journal: Journal of Clinical Oncology (2007)

3574 Background: Belinostat (PXD101), a HDAC inhibitor of the hydroxamate class has shown anti-tumor preclinical activity in combination with other standard chemotherapeutic agents. In Ph. I and II clinical trials the MTD for belinostat has been established at 1,000 mg/m 2 /d. This Ph I/II study assesses safety, and anti-cancer activity of belinostat administered in combination with C and/or P. Methods: Sequential cohorts of 3–6 patients (pts) with advanced solid tumors and PS 0–2 were recruited to determine the MTD of standard dose C and/or P with escalating doses of belinostat administered as a 30-min IV infusion daily for 5 days (d) every 21 d. C and/or P were administered 2–3 hours following infusion of belinostat on d 3. Results: 23 pts have been treated with a mean of 5 cycles (range 1 - 15) at 5 dose levels: C and belinostat (600 mg/m 2 ) (5 pts); P and belinostat (600 mg/m 2 ) (5 pts); C and P and belinostat (600 mg/m 2 ) (3 pts); C and P and belinostat (800 mg/m 2 ) (4 pts); C and P and belinostat (1,000 mg/m 2 ) (6 pts). Possibly drug-related grade 3 or 4 toxicities were thrombocytopenia (2), vomiting (1), sensory neuropathy (1), myalgia (1), and fatigue (1).No DLT was observed. One SAE (grade 1 T-wave morphology change) was graded as possibly drug-related. No QTcf greater than 500ms were reported. There are 2 confirmed PRs: 1 with heavily treated metastatic rectal cancer and 1 with gemcitabine pre-treated metastatic pancreatic cancer. An additional 11[E1] patients had SD for 2–15 cycles, with 4 being SD for &gt;10 cycles. One pt with mixed mullerian cancer of ovarian origin with SD had an 81% reduction in CA-125 to normal levels after 6 cycles. [E1]If you include MMMT pt as SD on radio. Conclusions: Belinostat with standard dose C and/or P is well-tolerated and shows clinical activity in heavily pre-treated patients with advanced metastatic disease. Recruitment to a phase II expansion in pts with recurrent ovarian cancer is ongoing. No significant financial relationships to disclose.
Abstract 18363: The Human Amniotic Mesenchymal Stem Cell -derived Ipscs Survive and Restore the Injured Hearts in an Immunocompetent Mouse Model of Myocardial Injury
Authors: Xiaohu ge, Wook-Jin Chung, Paul J. Kim, Yongquan Gong, Paul Chang, Robert Robbins, Rajesh Dash, Phillip C. Yang
Journal: Circulation (2012)

Background: Stem cells are known to restore the injured myocardium. This capability may improve if there is enhanced in vivo survival of the transplanted stem cells. The hAMSCs are isolated from amniotic membrane underlying the chorion of a human placenta and are located in the fetal-maternal border, demonstrating unique immunomodulatory properties characterized by CD59 +, HLA-G +, and HLA-DR- to suppress the host immune response. A single polycistronic lentivirus reprograms the hAMSCs robustly to generate MiPSCs. Hypothesis: The MiPSCs retain the immunomodulatory properties of hAMSCs to attenuate immune rejection in an immunocompetent mouse to restore the injured myocardium. Methods and results: 250K MiPSCs were transplanted into the LAD ligated heart of FVB mice. 250K hAMSCs were injected into the hearts of LAD ligated immunodeficient SCID mice as control. In vivo bioluminescence (BLI) demonstrated robust viability signal in the luciferase-transduced MiPSCs for 2 weeks in FVB mice (Figure 1). When comparing the MiPSC-treated vs. the control (hAMSC-treated) mice during the 4-wk follow-up period, cardiac MRI demonstrated significantly improved LVEF (29.75 vs. 22.45%, p&lt;0.05), decreased infarct % (21.47 vs. 31.06%, p&lt;0.05), and increased viable myocardial volume (78.07 vs. 67.9 cm3, p&lt;0.05). Notably, the MiPSCs did not form any teratoma. Conclusion: The MiPSCs exhibit unique immunomodulatory properties, which attenuate rejection by an immunocompetent mouse and significantly restore the injured heart. The MiPSCs may enable allogeneic cardiac stem cell therapy.
Sequence specificity of docetaxel (Doc) and the proteasome inhibitor PS-341 combinations in androgen-independent (AI) prostate cancer (CaP)
Authors: W. S. Holland, P. N. Lara, T. Kimura, T. Kenosi, D. R. Gandara, R. W. Devere White, P. H. Gumerlock
Journal: Journal of Clinical Oncology (2006)

13150 Background: AI CaP is an invariably fatal disease. While treatment with Doc, a microtubule-stabilizing taxane, improves survival, patient outcomes remain suboptimal. PS-341 inhibits degradation of cell cycle and tumor suppressor proteins resulting in cycle arrest and apoptosis. We hypothesized that the combination of Doc with PS-341 would abrogate the abnormal survival response seen in AI CaP and lead to improved tumor cell kill, but that results would be dependent on administration schedule due to interactive cell cycle kinetics. Methods: The PC3 cell line model of AI CaP was evaluated in vitro and in vivo to determine response to Doc or PS-341 alone, and in combination in sequences of PS-341→Doc, Doc→PS-341, and simultaneous (PS-341 + Doc). Cell cycle and protein analyses were performed by flow cytometry and Western blotting, respectively. For nu/nu mouse xenografts, 5 × 10 6 cells were injected subcutaneously into each flank. The agents were administered either together or 24hr apart, with all regimens given weekly [IP doses: Doc: 10 mg/kg; PS-341: 0.5 mg/kg]. Results: in vitro: Each combination showed an increased apoptotic sub-G1 population versus untreated cells, in addition to altered cell cycling in a sequence-specific manner. Of the combinations, PS-341 + Doc showed the largest sub-G1 while Doc→PS-341 had the lowest sub-G1 but the largest S-phase content; in vivo: PS-341 + Doc showed a cytotoxic effect (reduction in tumor volume) while the combinations of Doc→PS-341 and PS-341→Doc both showed growth inhibition (stabilization of tumor growth) as best response. Conclusions: Combinations of PS-341 and Doc have sequence specific cell cycle effects leading to increases in apoptosis (PS-341 + Doc) or cell cycle arrest (Doc→PS-341). Clinical validation of these findings is warranted. (ACS: CRTG-0019701-CCE) No significant financial relationships to disclose.
Anti-CD45 Monoclonal Antibody (MAb) Dose Optimization For Astatine-211 (211At)-Radioimmunotherapy (RIT) Of Relapsed Non-Hodgkin Lymphoma (NHL) In a Canine Model
Authors: Sofia H.L. Frost, Erlinda B. Santos, Brian W. Miller, Tom A. Bäck, Donald K. Hamlin, D. Scott Wilbur, Aimee L. Kenoyer, Shani L. Frayo, Oliver W. Press, Rainer Storb, Brenda M. Sandmaier, John M. Pagel
Journal: Blood (2013)
The combination of gemcitabine and cisplatin as neoadjuvant chemotherapy for early stage non-small cell lung carcinoma (NSCLC): an interim analysis of a phase II trial
Authors: A. Aydiner, M. Kiyik, S. Cikrikcioglu, F. Kosar, A. Gurses, A. Turna, A. Yazar, S. Dilege, T. Goksel, A. Cakan
Journal: Journal of Clinical Oncology (2005)

7303 Background: The objectives of this ongoing, open-label, single-arm, phase II trial were to evaluate the efficacy and safety of gemcitabine/cisplatin as neoadjuvant chemotherapy in patients with operable, early stage NSCLC. Methods: Chemonaive patients >18 to 70 years old with stage IB, IIA-B, and IIIA NSCLC and an ECOG performance status (PS) of 0–1 received gemcitabine (1000 mg/m2; iv) on days 1 and 8 plus cisplatin (75 mg/m2; iv) on day 1. The treatment was administered on a 21-day treatment cycle for 3 cycles, followed by surgery or radiotherapy if medically unfit for surgery. The follow-up period was 12 months after surgery. Results: At the time of this analysis, 43 patients, with a median age of 55.8 years, were enrolled. Most patients (47%) had stage IB, while 26% of the patients had stage II and 28% had stage IIIA disease. N0 and N2 nodal disease was observed in 74% and 26% of the patients, respectively. Overall, 70% of the patients had T2 primary tumors, 26% had T3, and 2% of the patients each had T1 and T0. At baseline, 19 patients had a PS of 0 and 24 patients had a PS of 1. The PS of the patients improved in each visit during the follow-up period; 33 (77%) patients were fully active and asymptomatic (PS 0) at the final visit. Of the 38 patients evaluable for clinical tumor response, 21 (55%) had partial response and 15 (40%) had stable disease, while only 2 (5%) had progressive disease. NCI-CTC grade 3–4 hematologic toxicities included neutropenia in 24 (56%) patients and thrombocytopenia in 6 (14%) patients. Non-hematologic toxicities were acceptable. Data on 24 of 43 patients were analyzed for surgery. The tumor resection rate was 88% (21 of 24). Two of 24 patients (8%) received radiotherapy following chemotherapy. Conclusion: Preliminary results show that the combination of gemcitabine/cisplatin is an effective and tolerable neoadjuvant treatment for patients with operable, early stage NSCLC. The final analysis of the data, including pathological complete response rate as well as the expression and correlation of the prognostic factors erbB-2, VEGF, Ki67, and p53 with efficacy parameters, will be presented at the meeting. No significant financial relationships to disclose.
Evaluation of 16 months of clinical use of cinacalcet in haemodialysis and peritoneal dialysis patients : an observational study in Belgium (ECHO-B)
Authors: Frederic D. Debelle, Gert Meeus, Michel Dhaene, Georges F. M. Cornet, Xavier Warling, Sofie Jamar, Evemie Schutyser, Michel Jadoul
Journal: Journal of the American Society of Nephrology (2010)
Uracil pharmacokinetics in a DPD-deficient patient with a novel <i>DPYD</i> mutation compared to volunteers with normal DPD activity.
Authors: M. C. van Staveren, H. Guchelaar, A. B. van Kuilenburg, J. Maring
Journal: Journal of Clinical Oncology (2010)

e13134 Background: Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the metabolism of 5-fluorouracil (5-FU). Patients with a partial or complete DPD deficiency are at risk to develop severe toxicity after 5-FU administration. Uracil (U) is degraded in dihydrouracil (DHU) in a similar way as 5-FU. An oral uracil test dose might be useful to determine the systemic DPD activity by measuring uracil and its metabolite dihydrouracil in plasma. DPD deficiency is hypothesized to result in higher uracil levels and a reduced turnover of uracil into dihydrouracil. Methods: Uracil (500 mg/m2) was administered to 11 healthy volunteers with normal DPD activity (≥ 6 nmol/mg/hour) and 1 patient with colorectal carcinoma with a novel DPYD mutation and decreased DPD activity (4.6 nmol/mg/hour). DPD activity was measured in PBMC, as determined as described earlier. Blood samples were taken at t= 15, 30, 45, 60, 80, 100, 120, 150, 180, and 220 or 240 min after oral uracil intake. U and DHU plasma levels were determined by HPLC-UV. Pharmacokinetic parameters Cmax, AUC and U/DHU ratios were calculated. The 95% confidence intervals of these parameters were determined by statistical analysis. Results: Mean±SD values of AUCuracil(T=180) and AUCdihydrouracil(T=220) in volunteers were 865.1±240.3 and 439.3±134.5 mg min/l respectively, Cmax uracil and Cmax dihydrouracil were 14.4±4.7 and 3.0±0.9 mg/l. The AUCuracil(T=180), AUCdihydrouracil(T=180), Cmax uracil and Cmax dihydrouracil of the DPD deficient patient were 941.9 mg min/l, 119.2 mg min/l, 11,2 mg/l and 0.9 mg/l. Mean±SD U/DHU ratios at t=100, 120, 150, 180 min in volunteers were 0.9±0.3; 0.5±0.2; 0.2±0.1; and 0.1±0.04. Ratio's of the patient were 5.9; 3.9; 1.7; and 0.7. Conclusions: AUCuracil and Cmax uracil of the patient with a partial DPD deficiency do not differ significantly compared to healthy individuals, whereas AUCdihydrouracil and Cmax dihydrouracil were significantly lower. The uracil/dihydrouracil ratios in the DPD deficient patient were higher and outside the 95% confidence interval of those of volunteers at all sample points. Uracil/dihydrouracil ratios may useful as a phenotypic test for DPD deficiency. No significant financial relationships to disclose.
Concordance of local and central laboratory hormone and HER2 receptor status in ECOG 2197
Authors: S. S. Badve, F. L. Baehner, R. Gray, B. Childs, T. Maddala, S. Rowley, S. Shak, N. Davidson, L. J. Goldstein, J. Sparano
Journal: Journal of Clinical Oncology (2007)

21022 Background: Central and local laboratory concordance for hormone and HER2 receptor measurement is of national interest. This study compares ER/PR/HER2 by local laboratories using immunohistochemistry (IHC) and central laboratories (IHC &amp; quantitative RT-PCR). Methods: Of 2952 patients in E2197, a case-cohort sample of 776 patients who either did (N=179) or did not recur was studied. Central IHC for ER/PR/HER2 was performed using single 0.6 mm microarrays; Allred score (AS) was used for ER/PR (AS&gt;2 = positive). Positive HER2 was 3+ staining in &gt;10% cells for Central IHC and 2+ or 3+ for Local IHC. RT-PCR analysis by Oncotype DX™ for ER/PR/HER2 was performed using pre-defined cutoffs of 6.5, 5.5 and 11.5 units, respectively. Hormone receptor (HR) pos was defined as ER &amp;/or PR pos. Results: Results from Local IHC (ER/PR in 776 &amp; HER2 in 517 pts) were compared with Central IHC (760 pts) and RT-PCR results (776 pts). The discordance between HR positivity by Local IHC and RT-PCR was very low. However, 12% of HR neg pts by Local IHC (38/321) &amp; Central IHC (39/326) were HR pos by RT-PCR. The relationship between ER and recurrence as a function of AS was examined. Patients with AS of 3–4 were found to be closer to the AS=2 group than to the AS&gt;4 group Patients with AS of 3–4 were found to be closer to the AS ÿ 2 group than to the AS &gt; 4 group (Est.HR for ER 0.97 for AS 3–4 vs. 0–2 and 0.46 for AS 5–8 vs. 0–2, and for PR were 0.84 for AS 3–4 vs. 0–2 and 0.41 for AS 5–8 vs. 0–2). Conclusions: There is a high degree of overall concordance among Local IHC, Central IHC, and Central RT-PCR for ER and PR. The degree of concordance is even greater for HR compared to ER or PR alone. Although the concordance with local labs for HER2 testing was poor, the concordance between Central IHC and RT-PCR was very high. The relatively high incidence (12%) of IHC HR neg pts who are HR pos by RT- PCR is notable. [Table: see text] [Table: see text]
Population pharmacokinetics (PK) of tremelimumab in patients (pts) with melanoma
Authors: D. Kang, E. Wang, D. Wang, M. Amantea, P. Hsyu
Journal: Journal of Clinical Oncology (2009)

3048 Background: Tremelimumab is a fully human monoclonal antibody targeted against CTLA4, a protein on T cells critical for regulating T-cell activities, which is under development for treatment of various cancers, including melanoma. Population PK analysis was conducted using concentration-time data from 450 pts, most with melanoma or solid tumors, enrolled in four phase I or II studies that evaluated PK, tolerability, and efficacy of single-agent tremelimumab. Methods: Tremelimumab was administered intravenously either as single dose or multiple doses every 4 or 12 weeks; doses varied between 0.01 and 15 mg/kg. PK was determined using nonlinear mixed-effect modeling implemented in NONMEM VI. Baseline characteristics, including body weight, ECOG score, age, sex, serum creatinine, AST, ALT, and bilirubin, and formulation effects were investigated as potential factors affecting PK. Tremelimumab plasma concentrations were determined using a sensitive, specific, validated ELISA assay. Results: A two-compartment linear model adequately described tremelimumab concentration-time data; an additive residual error model was employed on log-transformed data. Initial and terminal half-lives were 2.5 days and 22 days, respectively. Estimated parameter values were: 0.0109 L/hr for CL (clearance), 3.72 L for V1 (central volume of distribution), 0.0172 L/hr for Q (intercompartment clearance), and 3.31 L for V2 (peripheral volume of distribution). Females had 29.6% smaller V2 compared with males. Both CL and central V1 increased with weight. An ECOG score of ≥1 showed 20.2% increase in CL compared with a score of 0. New commercial formulation decreased CL by 18.5%. The model-predicted area under concentration-time curve value in females was 13.3% greater than males (p=0.5). None of the other covariates tested significantly affected PK. Furthermore, tremelimumab was tolerated in most pts at all doses tested. Conclusions: PK of tremelimumab were shown to be affected by weight, baseline ECOG score, and formulation. However, no effects other than weight were considered clinically significant enough to warrant treatment regimen change. Further investigation of PK-response relationships is warranted. [Table: see text]
Lenalidomide After Autologous Transplantation for Myeloma: First Analysis of a Prospective, Randomized Study of the Intergroupe Francophone Du Myelome (IFM 2005 02).
Authors: Michel Attal, Jean Luc Harousseau, Gerald Marit, Denis Caillot, Anne Marie Stoppa, Lofti Benboubker, Thierry Facon, Cyrille Hulin, Laurent Garderet, Thierry Lamy, Serge Leyvraz, Chantal Doyen, Mauricette Michallet, Laurent Voillat, Charles Dumonté, Murielle Roussel, Valery lauwers-Cances, Christelle Cristini, Chantal Escriva, marie-Odile Petillon, Claire Mathiot, Hervé Avet-Loiseau, Philippe Moreau
Journal: Blood (2009)
Efficacy of different regimens of adjuvant radiochemotherapy for glioblastoma
Authors: A. Scheda, K. Finjap, F. Lohr, J. Tuettenberg, M. Brockmann, F. Wenz, F. Wenz
Journal: Journal of Clinical Oncology (2007)

12531 Background: Purpose/Objective(s): We retrospectively analyzed the impact of different temozolomide (TEM) regimens in a group of patients treated for glioblastoma compared to patients only receiving postoperative radiotherapy. Methods: Between 01/2000 and 12/2003, 75 consecutive patients underwent radiotherapy. 52 patients received exclusively radiotherapy, 17 patients radio-chemotherapy with low-dose TEM (20 mg/m2) given in 2 daily single doses in combination with an inhibition of cyclooxygenase-2, 6 patients radio-chemotherapy with high-dose TEM (50mg/m2) followed by adjuvant TEM (150–200mg/m2) for 5 days during each 28-day cycle up to 6 cycles. Patients were monitored with MRI every 8 weeks. Aggressive treatment for recurrent disease consisted of re-operation, re-irradiation (fractionated stereotactic radiotherapy 12 x 3 Gy) and/or chemotherapy. Results: The groups treated with high-dose TEM and low dose TEM showed the longest overall survival (OS) (median OS 21 months and 17 months, respectively). Median OS of 9 months for the radiation alone group was condiserably shorter. The same positive trend on prolonged OS was confirmed when either only patients submitted to maximally radical resection or for patients with KPS&gt;70 were considered. No statistically significant difference was observed in terms of progression free survival (PFS). Conclusions: Patients treated with adjuvant TEM either inside or outside study protocols had survival times similar to other reports or randomized studies. The absence of influence of TEM on PFS could either depend on the unavoidable drawbacks and bias of retrospective investigations or on the definition of relapse used. Aggressive and early treatment for recurrent disease results in median survival times approaching 2 years. No significant financial relationships to disclose.