tbuckley/cabot-search huggingface dataset:
Weekly paclitaxel (PCT) in non-small cell lung cancer (NSCLC): Results in older or frail patients. A Spanish Lung Cancer Group Trial (GECP 00-02)
Authors: B. Massutí, C. Camps, J. R. Barceló, P. Garrido, N. Viñolas, I. Barneto, M. Guillot, I. Bover, M. Jiménez, C. Chaib
Journal: Journal of Clinical Oncology (2004)

8044 Background: NSCLC patients (p) frequently older with significant comorbidities and not considered suitable for platinum-based chemotherapy (CT). Weekly single-agent PCT offers potential for lower toxicity, increased exposure to the drug with alternative cytotoxic/cytostatic mechanisms. Methods: Stages IIIB (pleural effusion)-IV, > 70 y, creatinine clearance < 60 ml/min, cardiovascular diseases, stage II chronic bronchitis, untreated p, measurable disease (RECIST). Treatment schedule: Paclitaxel 80 mg/m2 d1,8,15 every 28 d. End-points: Response Rate, Toxicity, TTP, Survival, biological correlates. Results: 74 p, 44 evaluable for response, 63 for toxicity. Median age: 73 y with 11% older than 80 y. PS 0/1/2: 10/52/38%. Histology: Squamous (49%), Adenocarcinoma (40%). Metastatic sites: lung (88%), lymph nodes (48%), liver (28%), pleura (21%) with 53% of p with > 1 site. Stage IV (distant metastases): 78%. Median creatinine clearance: 73 ml/min. Comorbidities: Chronic bronchitis 41%; Heart disease 22%, Diabetes 20%, Renal disease 18%, Vascular disease 11%. Comorbidity as single inclusion criteria 19%; age and comorbidity (both inclusion criteria): 29%. Median delivered CT cycles: 3 (1–9). Response rate (ITT analysis): CR 2%, PR 21%, SD 41%. Disease control rate at first evaluation (3 months): 64%. Median survival time (MST) 9 m with 1-year survival probability 31%; MST older 70 y 9m, younger 70 y 6 m (p= 0.08); MST PS 0-1: 11 m, PS 2–3: 6 m (p= 0.05) Toxicities: 3 p G3 anemia, 1 p G3 thrombocytopenia without bleeding, 1 p G3 neutropenia without fever; 1 p G3 arrithmia, 2 p G3 hypersensitivity, 2 p G3 neurotoxicity, 3 p G3 asthenia. Conclusions: Weekly PCT is feasible and safe in NSCLC p not-suitable for platinum-based CT due to age or comorbidities. 23% ORR with disease control rate of 64% at 12 w in this group of p with median age 73 y, 83% Stage IV, 38% PS 2 and 49% with significant comorbidities. MST 9 months with significant differences according PS and trend to worse survival for younger p with comorbidity. Mild toxicity profile without toxic deaths. Results of COX-2, Stathmin and PGP expression will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Roche
Abstract 18117: Cardiopoietic Stem Cell Therapy In Heart Failure: The Multicenter Randomized C-cure Trial
Authors: Jozef Bartunek, Atta Behfar, Dariouch Dolatabadi, Miodrag Ostojic, Jo Dens, Marc Vanderheyden, Branko Beleslin, Christian Homsy, Marko Banovic, Badih El Nakadi, Michal Tendera, Scott Waldman, Willam Wijns, Andre Terzic
Journal: Circulation (2012)

Background Cardiopoietic stem cells improve left ventricular function and blunt pathological remodeling in preclinical models of heart failure. In this first-in-man trial we assessed the feasibilit...
Immunotherapeutic targeting of HSP90 client proteins in BRAF-inhibitor resistant melanoma
Authors: Ronald J Fecek, Simeng Wang, Walter J Storkus
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Therapy options for patients with advanced stage melanoma have improved steadily over the past decade, with recent clinical successes noted for BRAF inhibitors (BRAFi). BRAFi such as dabrafenib are highly specific for BRAF mutant, BRAFV600E, which is expressed in approximately 50
Prescription patterns for metastatic breast cancer patients previously treated with anthracycline and taxane: An assessment in a United States managed care database
Authors: L. A. Harris, Y. Yu, B. Donato
Journal: Journal of Clinical Oncology (2007)

17056 Background: There is a scarcity of literature documenting actual prescription patterns for metastatic breast cancer (MBC) patients. The objective of this study was to describe the pattern of dispensing chemotherapy agents among MBC patients previously exposed to anthracycline and taxane in the managed care setting. Methods: Study cohort was extracted from the PharMetrics database between 1/1999 through 6/2005, who were =18 years, enrolled =6 months with =2 ICD-9-CM codes for breast cancer (BC), =1 ICD-9-CM code for distant metastases, and =1 NDC/J-code for anthracycline and taxane. A 21 day treatment interval was assigned to all agents to identify treatment regimens. If types of agents in consecutive intervals were the same, they were collapsed into one regimen disregarding the sequence. Following the reference date, the dispense date of the first anthracycline or taxane prescription, whichever occurred later, the first regimen was treated as reference regimen. Following this regimen, sequential monotherapy or combination therapy was identified in a chronological order. Results: Of the 1,028 who met inclusion criteria, 67% (n=691) did not receive a sequential therapy. Of the 33% (n=337) who did, the first sequential regimen for 177 was monotherapy and 160 combination therapy. The most common agents within the monotherapy regimens were taxanes 28%, capecitabine 20%, and trastuzumab 18%. For combination, taxane/trastuzumab 9.4%, vinorelbine/trastuzumab 9.4%, and carboplatin/taxane 8.8%. Of those who received sequential therapy, 68% were retreated with a taxane; 34% with docetaxel and 46% with paclitaxel. Conclusions: In this study, the majority of the population did not receive sequential therapy. This may have been due to loss to follow up, the duration of the reference regimen (lasting throughout the study period(s) after collapsing), or treatment in the inpatient setting where chemotherapy agents are not identifiable in this claims database. Taxane was the most common agent received in the first sequential therapy, both for monotherapy and combination therapy. A high proportion of patients with sequential therapy were retreated with a taxane. No significant financial relationships to disclose.
Predictive gene expression patterns of response to adriamycin and cyclophosphamide (AC) in human breast cancers
Authors: A. Makris, C. Creighton, K. C. Osborne, S. Hilsenbeck, M. K. Harrison, P. J. Ostler, C. Spears, P. Brown, R. Elledge, J. C. Chang
Journal: Journal of Clinical Oncology (2007)

527 Background: Adriamycin and cyclophosphamide (AC) and docetaxel (D) are widely used in the treatment of breast cancer. We conducted a prospective, randomized, multicenter trial to discover predictive markers of AC and D and hypothesized that gene expression profiles can select appropriate patients who may respond to AC, and that these patterns are different from our published docetaxel (D) profiles Methods: One hundred and twenty patients were randomized to either 4 cycles of AC (60/600 mg/m 2 ) or D (100mg/m 2 ) prior to surgery. Core biopsies from 60 patients were obtained before treatment with neoadjuvant AC. Pathologic responses were assessed after AC. Gene expression patterns were determined using Affymetrix U133A GeneChips. Differential genes for AC response were then validated by QRT-PCR in an independent cohort of 33 patients treated with AC. Results: The median age was 48 yrs (range 30–72), clinical response rates were 57% (34/60), and pathological complete response (pCR) or near pCR (npCR) was observed in 22% (12/60) in AC arm. Differential expression between sensitive and resistant tumors with a low false discovery rate (FDR 5–10%) was obtained. Of these 82 differentially expressed genes, pathways up-regulated in sensitive tumors included TOP2A, metabolism (LYZ), survival (CFLAR, CASP3), cell cycle (MKI67), cytokines and other inflammatory genes. This molecular portrait for AC was not predictive of docetaxel response. By QRT-PCR of 4 genes (LYZ, CFLAR, MKI67 and TOP2A) in the independent tumor set, LYZ was predictive of AC pathologic complete response. Additional genes will be validated in the second cohort. Conclusions: The molecular profile for AC is different from the docetaxel expression profile. This potential predictive test may allow selection of the most appropriate chemotherapy schedule for women with breast cancer. No significant financial relationships to disclose.
Treatment of primary CNS lymphoma with induction high-dose methotrexate, temozolomide, rituximab followed by consolidation cytarabine/etoposide: A pilot study with biomarker analysis
Authors: S. Issa, J. Hwang, J. Karch, J. Fridlyand, M. Prados, T. Batchelor, K. Aldape, C. Haqq, L. Damon, J. Rubenstein
Journal: Journal of Clinical Oncology (2006)

7595 Background: There is currently no consensus on the optimal treatment for patients diagnosed with primary CNS lymphoma (PCNSL). Between 2001–2004, UCSF PCNSL patients were treated with combination high-dose methotrexate, temozolomide, rituximab (MTR) as induction therapy. Patients in CR with this regimen were treated with high-dose cytarabine plus etoposide as consolidation. The purposes of this study were: (1) Pilot analysis to determine the safety and efficacy of intensive methotrexate-based induction therapy followed by high-dose consolidation with elimination of whole brain irradiation; (2) Analysis of molecular markers in PCNSL which predict sensitivity to chemotherapy and outcome. Methods: 21 untreated, CD20 +, immunocompetent PCNSL patients were treated with combination methotrexate (8 gm/m²), temozolomide (150 mg/m²/day)and rituximab (375 mg/m²). Patients in CR received consolidation cytarabine (2 g/ m² x 8 doses) plus etoposide (40 mg/kg over 96 hours). IHC analysis of potential biomarkers predictive of outcome was performed on paraffin sections from these patients. Candidate markers for validation were selected by gene expression analysis of an independent, multicenter dataset of 20 cases. Results: Mean age was 58.6 y (range 40–81). Median KPS was 60. MTR and cytarabine/etoposide consolidation was well-tolerated with no treatment-related mortality or evidence for neurotoxicity. One case of post-remission cytopenia occurred after consolidation and resolved spontaneously. Eleven patients (52.4%) attained CR with induction; eight received consolidation; three patients in CR deferred consolidation. Median PFS was 11.5 months. Median OS for all 21 patients has not yet been reached with median follow-up of 27.5 months. Expression of the apoptotic regulator DAP-1 by lymphoma cells as determined by IHC was associated with improved PFS (p&lt;0.028) and OS (p&lt;0.021). Conclusions: Combination MTR followed by intensive consolidation appears to be well tolerated in PCNSL. PFS appears at least similar to regimens that contain whole brain irradiation. A larger phase II study has been initiated to evaluate this regimen in a multicenter setting. [Table: see text]
The expression of P-gp, Bcl-2 and VEGF in epithelial ovarian carcinoma and their significance
Authors: W. Gang, F. Luo, G. L. Li, J. Cheng, X. Shi
Journal: Journal of Clinical Oncology (2007)

16075 Background: To investigate the expression of P - gp,Bcl-2 and VEGF in epithelial ovarian carcinoma as well as their significance. Methods: Expression of P- gp,Bcl-2 and VEGF were examined in 72 epithelial ovarian carcinoma by immunohistochemisty (method of S - P) . Results: The positive expressions of P - gp,Bcl-2 and VEGF in patients with ovarian carcinoma were 51.4%,54.2%,56.9% respectively .Compared with those in ovarian benign tumors and normal controls, such expression level were significantly higher ( P &lt; 0.05). The expression of P - gp was positively correlated with the expression of VEGF( P &lt;0. 05) while the expression of VEGF was positively correlated with the expression of Bcl-2 ( P &lt;0. 05). Univariate analysis showed worse disease-free survival in the patients with positive expression of P-gp or VEGF than in those with negative expression of P -gp or VEGF( P &lt; 0. 05). Multivariate analysis of clinical and pathological data by Cox-regression method showed that the expression of P - gp or VEGF and co- expression of these three indexes were correlated with poor prognosis. Conclusions: Over-expression of P - gp,Bcl-2 and VEGF is correlated with drug resistance of clinical chemotherapy and survival rate in ovarian cancer . To examine these 3 indexes in ovarian cancer is helpful to evaluate response to clinical chemotherapy as well as to predict the prognosis. No significant financial relationships to disclose.
Neuroprotective effects of pharmacologically induced hypothermia with delta-opioid receptor agonist DADLE and cannabinoid receptor agonist WIN55,212-2 during extracorporeal life support for cardiac arrest
Authors: G. Tong, Alessio Rungatscher, Daniele Linardi, Alice Giacomazzi, Maddalena Tessari, Tiziano Menon, Alessandro Mazzucco, Giuseppe Faggian, F. Berger, K. R. Schmitt
Journal: Circulation (2014)
SDF-1α up-regulates expression of the chemokine receptor CXCR4 in PC3 cells via a MEK-ERK dependent NF-κB activation
Authors: Promil Kukreja, Asim B. Abdel-Mageed, Debasis Mondal, Krishna C. Agrawal
Journal: Cancer Research (2005)

5240   Bone metastasis in prostate cancer (PC) results from a complex cascade of events initiated by trans-endothelial migration (TEM) of PC cells to the bone marrow microenvironment. We tested the hypothesis that enhanced expression of the chemokine receptor, CXCR4 in PC cells is dependent upon SDF-1α mediated activation of NF-κB, which plays a crucial role in their adhesion to the bone marrow endothelium and TEM. PC3 (bone metastatic PC cell line) and LNCaP (lymph node metastatic PC cell line) cells were treated with SDF-1α (100 ng/ml) for 6 or 24 hr. RT-PCR analysis at 6 hr showed an increased CXCR4 mRNA expression (3-4 fold) in PC3 cells but not in LNCaP cells; by 24 hr this induction in PC3 cells returned to basal levels. Transient transfection of PC cells with NF-κB-luciferase reporter plasmid (2 μg) followed by exposure to SDF-1α showed enhanced levels of NF-κB-dependent transcriptional activity in PC3 cells but not in LNCaP cells. SDF-1α stimulation increased (200-225 %) PC3 cells adhesion to the confluent vascular endothelial cell (HUVEC) monolayer and enhanced (80-100 %) TEM. Co-incubation of PC3 cells with monoclonal CXCR4 antibody (1 μg/ml) blocked their adhesion and TEM through endothelial cells. Transfection of LNCaP cells with a CXCR4 expression plasmid enhanced adhesion ability of these cells to HUVECs. Suppression of NF-κB activity in PC3 cells by a mutant I-κB-α super-repressor adenoviral vector decreased the CXCR4 mRNA expression by 2-3 fold and inhibited adhesion and TEM (50-80 %) of PC3 cells. Over-expression of p65 subunit of NF-κB by transient transfection of PC3 cells with pCMV-p65 expression plasmid (3 μg per 5x10 5  cells) up-regulated the CXCR4 mRNA expression and cell surface CXCR4 receptor expression (2-3 fold), and increased the adhesion (50-80 %) even in the absence of SDF-1α. TEM of these cells was further increased (80-100 %) in response to SDF-1α gradient (10 ng/ml). In contrast, introduction of pCMV-p50 expression plasmid in PC3 cells did not affect CXCR4 gene expression. Treatment of PC3 cells with SDF-1α up-regulated NF-κB protein expression within 15-30 min, which correlated with IκBα phosphorylation. The p42/44 MAPK (Erk 1/2) levels in these cells followed a biphasic pattern with early activation of Erk 1/2 within 15 min and then again at 3-4 hr after SDF-1α treatment. Phosphorylation of IKKα was observed within 30 min, which was blocked by PD98059 (MEK inhibitor). SDF-1α induced NF-κB reporter activity was also blocked by co-treatment of PC-3 cells with PD98059. These data suggest that SDF-1α induced NF-κB activation in PC3 cells is dependent on MEK-ERK signaling cascade and the resultant expression of CXCR4 plays a significant role in adhesion and TEM of bone metastatic PC3 cells through the vascular endothelial cells.
Adjusting the dose of intravenous ondansetron plus dexamethasone to the emetogenic potential of the chemotherapy regimen.
Authors: P J Hesketh, T Beck, M Uhlenhopp, M G Kris, J D Hainsworth, W G Harker, J R Cohen, E Lester, J F Kessler, D Griffen
Journal: Journal of Clinical Oncology (1995)

PURPOSE This pilot, open-label study evaluates the antiemetic efficacy and safety of a single 20-mg intravenous (IV) dose of dexamethasone combined with a single IV dose of ondansetron (32, 24, or 8 mg) in patients receiving highly emetogenic (HE), moderately high emetogenic (MHE), or moderately emetogenic (ME) chemotherapy, respectively. PATIENTS AND METHODS One hundred forty-six patients received a single 20-mg IV dose of dexamethasone over 15 minutes beginning 45 minutes before chemotherapy and either a single 32-, 24-, or 8-mg IV dose of ondansetron over 15 minutes beginning 30 minutes before chemotherapy. Patients were evaluated for emetic episodes, extent of nausea, and adverse events for 24 hours after chemotherapy. RESULTS Complete response (no emetic episodes) was noted in 72% (95% confidence interval [CI], 60% to 84%), 88% (95% CI, 79% to 97%), and 77% (95% CI, 63% to 92%) of patients in the HE, MHE, and ME categories, respectively. The proportion of patients who experienced no nausea on the posttreatment assessment was 51% (95% CI, 37% to 64%), 69% (95% CI, 56% to 81%), and 47% (95% CI, 29% to 65%), respectively. The antiemetic regimens were all well tolerated. The proportion of patients with any drug-related adverse events did not vary across the three study groups despite the range of ondansetron doses and variety of chemotherapy regimens. Mild headache was noted in 28% of patients. Other adverse events, all of which were noted in fewer than 10% of patients, included lightheadedness, fatigue, dizziness, and constipation. CONCLUSION A single IV dose of either 8, 24, or 32 mg of ondansetron combined with a single 20-mg IV dose of dexamethasone resulted in good control of acute emesis across a wide spectrum of chemotherapy regimens. Nausea control proved somewhat more difficult, with approximately 50% of patients in the HE and ME emetogenic categories experiencing some degree of nausea. The results of our pilot study suggest that adjusting the dose of ondansetron to the intrinsic emetogenicity of the chemotherapy regimen permits a more efficient use of ondansetron while maintaining good antiemetic control. Such an approach appears worthy of further investigation.
A phase Ib study of pertuzumab (P), a recombinant humanized antibody to HER2, and docetaxel (D) in patients (pts) with advanced solid tumors
Authors: G. Attard, J. J. Kitzen, J. de Bono, J. Verweij, L. Pronk, J. Zhi, S. P. Blagden, S. E. Reade, G. Zugmaier, M. J. de Jonge
Journal: Journal of Clinical Oncology (2005)

3166 Background: P represents the first in a new class of targeted therapeutics known as HER dimerization inhibitors (HDIs). It blocks ligand-associated heterodimerization of HER2 with other HER-kinase family members, thereby inhibiting intracellular signaling. Study endpoints: determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLTs) of P and D, and the pharmacokinetic (PK) interaction. Methods: DLTs are assessed in cycle 1 and defined as non-hematological toxicity ≥ grade 3, grade 4 neutropenia of > 7 days, thrombocytopenia grade 4. If DLT is observed in ≥ 2/6 pts at a dose level, MTD is exceeded. Pts are treated with a fixed dose of 1050 mg of P and an escalating dose of D as an IV infusion on day 1, q 3 weeks. Three dose levels of D are explored: 60, 75, and 100 mg/ m2. Results: To date, a total of 8 pts (6 males) have received 36 cycles, median 5 (range 1–9). Mean age: 59.5 years, PS 0/1: 5/3 pts. Tumor types: prostate (4), ovarian (2), head & neck (1) and melanoma (1). At dose level D 75 mg/ m2, 2 pts developed DLTs: grade 3 diarrhea and fatigue, and febrile neutropenia, respectively. None of 6 pts treated at dose level 1 developed DLTs. Most frequent grade 1/2 toxicities per cycle included: diarrhea 36% (grade 3 6%), fatigue 31% (grade 3 6%), mucositis 17%, and nausea 8%. Neutropenia and leukopenia grade 3/4 occurred in 28% and 19% of cycles, respectively. Preliminary data from 8 pts suggest that PK parameters of D are not altered in combination with P. Mean clearance of D single agent versus D combined with P is 59 L/h ± 14 and 68 L/h ± 16, respectively. Tumor assessment: 1 PR, 5 SD and 1 progression. Conclusions: The RP2D will be 60 mg/m2 D and 1050 mg of P but further evaluation of D at 75 mg/m2 and P at 420 mg (840 mg loading dose) q 3 weeks is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Ltd., Hoffmann-La Roche Boehringer Ingelheim, Celgene, Novartis, Oncolytics Biotech, Topotargets Hoffmann-La Roche, GlaxoSmithKline Hoffmann-La Roche, Novartis, Quintiles Oncology
Abstract P2-12-14: The effect of low intensity exercise for mental status and quality of life of Japanese early breast cancer patients
Authors: Makiko Kamio, Kazumi Kawase, Hiroko Nogi, Ken Uchida, Hiroshi Takeyama
Journal: Cancer Research (2015)

Abstract Objective: Breast cancer is one of the most common cancers, and it accounts for 20% of malignant tumors of women. Psychological damage of the breast cancer patient is serious. In our institution, approximately 30% of the early breast cancer patients diagnosed as depressed mental status before operation. Breast cancer patients have to receive hormone therapy, chemotherapy, and radiation therapy for a long term after operation. Depressed mental status affects execution of the treatment, and the interruption of the treatment brings the risk of cancer recurrence. As a treatment for depressed mental status of cancer patients, medication and psychotherapy are common, but some previous reports showed exercise is effective. Exercises provided in these reports were various kinds and strength, and the standard prescription is not established. We investigate the effect of walking program as a mild aerobic exercise, whether it improves the depressed mental status and quality of life (QOL) of breast cancer patients. Methods: 25 early breast cancer patients were recruited. Depressed mental status and QOL were assessed by Center for Epidemiologic Studies Depression Scale (CES-D) and Medical Outcomes Study 36-item Short Form Health Survey (SF-36). Physical activity was measured by accelerometer (Lifecorder PLUS, Suzuken), and estimated using metabolic equivalent foe task (MET). Participants mounted accelerometer after discharge, and baseline physical activity was recorded till 1 month after operation. After recording baseline physical activity, we instructed to perform walking or mild aerobic exercise. Scores of CES-D and SF-36, and physical activity data were measured again after two months. Results: Physical activity after intervention was significantly increased as compared to baseline (8.5±5.5 vs 12.3±6.9 MET.h/week, p=0.02 ). At pre-operation phase, nine patients (36%) regarded as depressed mental status by CES-D, and depressed patients decreased to five at the time of 3 months after operation. A subscale of SF-36 ( mental health ) reduced significantly compared with pre-operation and 3 months after operation ( p&amp;lt;0.01 ). Physical activity after intervention was correlated with the scores of CES-D and all subscales of SF-36. Conclusion: This study demonstrated the possibility that walking program as a mild exercise improves mental status and QOL of perioperative breast cancer patients. It is necessary to examine in more detail for clinical application. Citation Format: Makiko Kamio, Kazumi Kawase, Hiroko Nogi, Ken Uchida, Hiroshi Takeyama. The effect of low intensity exercise for mental status and quality of life of Japanese early breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-12-14.