tbuckley/cabot-search huggingface dataset:
High-dose chemotherapy followed by autologous stem-cell transplantation for Hodgkin disease using CVB as conditioning regimen
Authors: R. A. Avila, J. A. Valdéz, G. Caeiro, A. L. Basquiera, A. G. Sturich, A. R. Berretta, J. J. García
Journal: Journal of Clinical Oncology (2007)

17505 Background: Autologous stem-cell transplantation has become a widely used therapy in Hodgkin's disease. We analysed outcome, overall survival (OS) and time to progression (TTP) in relapsed patients with Hodgkin's disease undergoing autologous stem-cell transplantation (ASCT) in a single institution. Methods: Between 1996 and 2006, 28 patients (19 males and 9 females; median age 31 years old, range 10–63) underwent high dose chemotherapy with CVB regimen (cyclophosphamide 6 gr/m 2 , VP-16 2.400 mg/m 2 , and BCNU 450 mg/m 2 ) with autologous stem-cell support. Before transplantation, 20 patients had received two lines of chemotherapy and 8 patients, three lines or more. At time of transplantation 12 (42.8%) patients were in complete remission and 16 (57.2%) in partial remission after rescue chemotherapy. The graft consisted of bone marrow (n: 6) or peripheral blood stem cells (n: 22). Results: The 100-day mortality rate was 3.57 %. With a median follow-up of 36 months for the surviving cohort, the median time of TTP and OS was of 31.4 and 55.63 months respectively and the five years TTP and OS were of 45% and 47% respectively. The most common toxicities presented were febrile neutropenia (100%) and mucositis (92%), both of them resolved completely before discharged. Patients who achieved complete response (n=20) after transplantation (evaluated at 100-day) had a better OS than patients who achieved partial response (n=8) (HR: 0.11; CI: 95% 0.03–0.49; p:0. 0036). Conclusions: High dose chemotherapy using CBV as conditioning regimen followed by ASCT is an effective treatment to achieve complete remission, which is associated with better survival in our series. This regimen presented acceptable toxicity and low mortality. No significant financial relationships to disclose.
Randomized, phase I, and pharmacokinetic (PK) study of RAD001, an mTOR inhibitor, in patients (pts) with advanced hepatocellular carcinoma (HCC)
Authors: L. Chen, H. S. Shiah, C. Y. Chen, Y. J. Lin, P. W. Lin, W. C. Su, J. Y. Chang
Journal: Journal of Clinical Oncology (2009)

4587 Background: RAD001, an orally administered, novel mTOR inhibitor has recently been extensively evaluated in cancer therapy. Up-regulation of mTOR expression has been noted in 40–45% of HCC, and preclinical studies suggest mTOR inhibitor can effectively inhibit proliferation of HCC cells as well as growth of HCC xenograft in mice. In addition, cytochrome P450 system is known to involve in metabolism of rapamycin analogues, and elimination of RAD001 is impaired in pts with hepatic dysfunction. The study aims to define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and PK of daily- and weekly-dosing RAD001 in advanced HCC pts. Methods: Advanced HCC pts who were not feasible for or progressed after local therapy (surgery, percutaneous ablation or transcatheter arterial chemoembolization), ECOG PS 0–2, Child-Pugh's score &lt; 8, and adequate hepatic, renal and hematological functions were eligible. The doses of RAD001 for daily-dosing arm would be escalated from 2.5, 5.0, 7.5 to 10.0 mg, and from 20, 30, 50 to 70 mg in weekly-dosing arm. Four weeks of treatment was regarded as one cycle. PK samples were collected on days 1 of cycle 1 and 2. Results: A total of 36 pts (M/F 34/2; median age 58.5, range 28–75; Child-Pugh's class of A/B 31/5) were enrolled. Number of pts with DLT/enrollment for dose level I, II, III and IV in daily arm was 1/6 (grade 3 hyperbilirubinemia), 1/6 (grade 4 thrombocytopenia), 0/3 and 2/3 (grade 3 diarrhea and rectal bleeding in 1 and grade 3 diarrhea and cardiac ischemia in 1), respectively; whiles in weekly arm was 0/3, 1/6 (grade 3 ALT elevation), 0/3 and 1/6 (grade 3 infection), respectively. MTD for weekly- and daily- dosing schedule was 70 mg and &lt;7.5 mg, respectively. Reactivation of HBV and HCV was observed in 4 and 1 pts, respectively. The disease control response (DCR) of 31 evaluable pts was 61% (10/16) and 46.7% (7/15, including one PR) of pts receiving daily and weekly treatment, respectively. However, the DCR for weekly-dosing pts received &gt;50 mg was 75% (4/6). Conclusions: Patient accrual is ongoing to complete. However, preliminary data suggest RAD001 is moderately active in stabilizing the progression of HCC, and PK data will be important to determine the optimal dosing schedule of RAD001 for HCC pts. [Table: see text]
Targeted exercise for muscles that support the spine reduces low back pain, Cochrane review shows
Authors: Susan Mayor
Journal: BMJ (2016)

Targeted exercise to improve the use and coordination of muscles that support and control the spine is effective in relieving low back pain and improves functioning but no more so than other forms of exercise, a Cochrane review has found.1 It said that the choice of exercise for chronic low back pain should be based on the patient’s or therapist’s preferences.

The review’s authors …
Recombinant human ACE2 as a novel biotherapeutic for the treatment of patients with cancer.
Authors: H. Samonigg, T. Bauernhofer, R. Schaefer, B. Peball, E. Janzek, M. Schuster, H. Loibner
Journal: Journal of Clinical Oncology (2010)

e13653 Background: Angiotensin Converting Enzyme 2 (ACE2) is the key counterbalancing enzyme of the Renin Angiotensin System (RAS) and is expressed in most tissues. ACE2 degrades Angiotensin II (Ang II) to yield Angiotensin (1–7) (Ang(1–7)). Ang II increases blood pressure and is pro-inflammatory, angiogenic, a potent mitogen and increases vascular permeability. In contrast, Ang(1–7) has vasodilatory, anti-inflammatory, anti-angiogenic and antiproliferative properties. There is evidence that an activated RAS and elevated Ang II levels support tumor growth. A novel biological approach for cancer treatment thus is based on the utilization of ACE2 to degrade elevated Ang II to generate Ang(1–7). In this regard we are developing recombinant soluble ACE2 (rhACE2) for biologic therapy of diseases with an imbalanced RAS. rhACE2 was investigated in a phase I study in healthy volunteers and no side effects or toxicities were found. Methods: In order to explore the role of elevated Ang II on formation of malignant effusions, we have assessed Ang II levels in plasma and malignant effusions of patients with various solid cancers, using a commercially available Enzyme Immunoassay. Furthermore, the potential of rhACE2 was explored to degrade elevated Ang II in plasma of cancer patients ex-vivo. Results: In 15/24 patients (63%) plasma Ang II was elevated (> 16 pg/ml). Median plasma Ang II was 75 pg/ml (19-496 pg/ml). Six patients also presented with elevated Ang II in malignant effusions. A significant correlation between volume of effusions and Ang II levels in plasma was seen, suggesting that elevated Ang II contributes to formation of effusions. Ex-vivo treatment with 5μg/ml rhACE2 of undiluted heparinized plasma samples or effusions of cancer patients led to a rapid degradation of elevated Ang II. Conclusions: Treatment with rhACE2 of cancer patients with malignant effusions may cause reduction of elevated Ang II and increase production of Ang(1-7). This may lead to beneficial effects such as decreased formation of effusions, retarded proliferation of malignant cells, reduced angiogenesis and local inflammation. We have applied for a clinical study with rhACE2 in advanced cancer patients with elevated Ang II levels to test these hypotheses. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Apeiron Apeiron Apeiron
A novel paradigm in the treatment of solid tumors with TNFα: TNFerade biologic (Ad<sub>GV</sub>EGR.TNF.11D) gene therapy approach to drug delivery.
Authors: R. R. Weichselbaum, M. Kovacevic, R. Meng, G. Blatner, M. O. Thornton
Journal: Journal of Clinical Oncology (2010)

e13533 Background: Studies demonstrate tumor necrosis factor alpha (TNFα), if administered so that systemic toxicity can be controlled, is a useful anticancer agent. A gene therapy approach, using intratumoral injections of an adenovector expressing TNFα, is one way to potentially maximize antitumor activity and minimize systemic toxicity. Methods: AdGVEGR.TNF.11D (AdGVTNF) represents such an approach. AdGVTNF is a second-generation (E1-, partial E3-, and E4-deleted) adenovector carrying the transgene encoding for TNFa. The chemo + RT stress-inducible EGR-1 promoter was used upstream from the transgene to ensure maximal TNFα gene expression. Results: There is a known therapeutic synergy between RT and TNFα for local tumor control. Additionally, preclinical studies demonstrated AdGVTNF +IR suppressed lymph node metastasis in two preclinical models and this effect was CD8+ dependent. Results demonstrated that AdGVTNF +IR improved antigen specific tumor infiltration of CD8+ cells. Data also suggested that AdGVTNF increased dendritic cell maturation and T cell attractant chemokine production compared with IR alone. Preclinical testing has also demonstrated that chemotherapeutic agents can activate the Egr-1 promoter in AdGVTNF and allow for the expression of TNFα. Additionally, in in-vivo testing, the combination of gemcitabine and AdGVTNF delayed tumor growth better than either agent alone. AdGVTNF has been studied in clinical trials in: sarcoma, esophageal, pancreatic, melanoma, head and neck, and rectal cancers. In these indications, repeat intratumoral injections of AdGVTNF in combination with RT and chemo have been feasible and generally well tolerated. Results have shown promising tumor response and indications of increased survival. Conclusions: AdGVTNF represents a new technology to deliver TNFα directly to tumor tissue to reduce systemic toxicity. AdGVTNF adds the flexibility of activation by radiation and/or other chemotherapy treatment, and may activate immune mechanisms to control tumor metastases. This novel agent is in phase III development for locally advanced pancreatic cancer and represents a new paradigm in patient treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GenVec GenVec GenVec
Phase II study of capecitabine and trastuzumab combination chemotherapy in patients with HER2-overexpressing metastatic breast cancers after failure of both anthracyclines and taxanes
Authors: T. Ishida, T. Kiba, M. Takeda, K. Matsuyama, S. Teramukai, N. Masuda, Y. Takatsuka, S. Noguchi, M. Fukushima, N. Ohuchi
Journal: Journal of Clinical Oncology (2008)

1117 Background: No studies have investigated the activity of capecitabine and trastuzumab in patients with HER2-overexpressing breast caner after failure of both anthracyclines and taxanes. Methods: Primary endpoint of this phase II study was overall survival and secondary objectives were progression free survival and response rates. Pts were treated with weekly trastuzumab given at a dose of 2mg/kg/day over 90 minutes (4mg/kg/day on the first infusion) and capecitabine given at a dose 1,657 mg/m2/day during 21 days with a subsequent pause of 7 days. This cycle was repeated every 28 days up to 6 cycles. Response assessments were scheduled after 2, 4 and 6 th cycles. ECOG PS was 0–2. Results: From June 2003 and May 2006, 39 pts enrolled. 1 pt dropped out before treatment: 1 pt was treated off-protocol immediately after enrollment. A total of 153.5 cycles were delivered with a median of 4 cycles (range, 1–6). Median age 53 (30–69). Median follow-up time 23.5 months. Median overall survival times and progression-free survival times 23.5 months and 4.2 months. Survival at 1 year and 2 year 83.8% and 48.6%. Response rate 21.6% (95% CI, 9.9 to 38.2%)(CR/PR/SD/PD/NE 5.4/16.2/48.7/ 21.6/8.1%). Clinical benefit rate 24.3% (95% CI, 11.9 to 41.2%). Grade 1–2 hand-foot syndrome and elevated AST, ALT, ALP, T- bil, γ-GTP occurred in 19 (51.3%), 17 (45.9%), 13 (35.1%), 19 (51.3%), 13 (35.1%), 12 (32.4%). Grade 3 toxicities: hand-foot syndrome (5.4%), neutropenia (2.7%), elevated γ-GTP (2.7%), diarrhea (2.7%), constipation (2.7%). No grade 4 toxicities and treatment-related death. Conclusions: The combination of capecitabine and trastuzumab is active and well tolerated in patients with HER2- overexpressing breast caner after failure of both anthracyclines and taxanes. No significant financial relationships to disclose.
Lymphocyte and Hematopoietic Stem and Progenitor Cell (HSPC) Subsets Mobilized By Either Plerixafor or G-GCSF: A Retrospective Comparison of Grafts Harvested in Healthy Allogeneic Stem Cell Donors
Authors: Georgine E. De Greef, Eric Braakman, Wendimagegn G Alemayehu, Larissa De Graaf, Peter van Geel, Meriam Grootes, Carla Engelman, Eefke Petersen, Otto Visser, Vladan Vucinic, Dietger Niederwieser, Jan J. Cornelissen
Journal: Blood (2014)
Abstract 20107: The Matricellular Protein CCN2/CTGF Attenuates Ventricular Remodeling by Enhancing Scar Healing after Myocardial Infarction
Authors: Ole J Kaasboell, Geir Florholmen, Magnus Aronsen, Erhe Gao, Ingvild T Moe, Walter J Koch, Ivar Sjaastad, Shakil M Ahmed, Håvard Attramadal
Journal: Circulation (2014)

We have previously shown that left ventricular (LV) remodeling after myocardial infarction (MI) is attenuated in transgenic mice with cardiac-restricted overexpression of CCN2 (Tg-CCN2) regardless of reperfusion of the ischemic area or not. Thus, the aim of this study was to resolve to what extent the role of CCN2 in scar healing may mechanistically contribute to attenuation of LV dilatation after MI.  MI was induced by ligation of the left coronary artery in Tg-CCN2 and in non-transgenic control (NTC) mice. Area of necrosis and LV dimensions were determined by cardiac MRI. Primary cultures of cardiac fibroblasts (cFBs) were prepared from NTC mice and stimulated with or without recombinant CCN2 (rCCN2; 200 nmol/L).  Area of necrosis 24 hours after induction of MI was similar in Tg-CCN2 and NTC mice. Serial cardiac MRI examinations at day 1, 7, 14, and 42 after induction of MI revealed that CCN2 engendered robust inhibition of LV dilatation during the first week after MI, i.e. the period of infarct dilatation (LV end-diastolic volume at day 7: 97±9 vs. 136±7 μL in Tg-CCN2 vs. NTC mice; p  In conclusion, this study demonstrates that CCN2 enhances healing of MI and that the accelerated scar tissue formation during the first week after MI contributes to reduced LV dilatation and reduced incidence of infarct rupture. CCN2 stimulates an inflammatory cFB phenotype that promotes senescence of cFBs, providing a plausible mechanism for the enhanced, yet limited scar formation.
Improvement of dendritic cell therapy in glioblastoma multiforme WHO 4 by Newcastle disease virus.
Authors: J. Nesselhut, D. Marx, D. Lorenzen, N. Cillien, W. Goebel, R. Y. Chang, W. Brockmann, J. H. Peters, K. Nesselhut, F. Fändrich, T. Nesselhut
Journal: Journal of Clinical Oncology (2011)

2508 Background: Glioblastoma multiforme (GBM, WHO grade 4 glioma) is an aggressive disease with an unfavorable prognosis. The current first line treatment comprises radical operation and radiotherapy combined with temozolomide chemotherapy. The reported median overall survival time after primary diagnosis is less than 15 months. After failure of first-line therapy there is currently no effective therapy, and side effects from further treatments may potentially impair quality of life. We report that immunotherapy with monocyte-derived dendritic cells (MoDC) combined with oncolytic Newcastle Disease Virus (NDV) can improve the efficacy of dendritic cell based immune therapy for relapsed GBM. Methods: After isolating monocytes from peripheral blood of n=37 patients with stage IV GBM who failed first-line radio-chemotherapy (PFI: 8 months), MoDC were generated using standard protocols. In 19 patients, NDV was added to the MoDC on day 5. These patients were also pretreated with an infusion with NDV one day before vaccination. The MoDC were harvested on day 7 of culture and administered to the patients intradermally. Results: Improvement of the clinical response was observed in patients, who received combination of NDV with MoDC vs. MoDC alone (47% vs. 11%). The median survival after onset of DC-therapy was 3 months with MoDC alone and 10 months (23 months after primary diagnosis) in combination with NDV. The 1- year-survival rates after onset of DC therapy were 6% and 32%, respectively. The therapy was well tolerated without any major side effects. IFN-gamma Elispot analyses from patients who received NDV injections and NDV-primed MoDC show that MoDC primed with NDV can induce a specific CD4 and CD8 T-cell response against NDV whereas healthy donors show no specific T-cell response. Conclusions: The efficacy of dendritic-cell based therapy for GBM can be improved by combination with NDV and may prolong overall survival of patients after failure of first-line therapy. For a first time we demonstrate that NDV primed MoDC induces a NDV specific T-cell response in humans, which may lead to in-vivo lysis of NDV-infected tumor cells.
Interleukin-21 (IL-21) activity in patients (pts) with metastatic melanoma (MM).
Authors: T. M. Petrella, R. Tozer, K. Belanger, K. J. Savage, R. Wong, S. Kamel-Reid, V. Tron, B. Chen, N. N. Hunder, E. A. Eisenhauer
Journal: Journal of Clinical Oncology (2010)

8507 Background: IL-21 is a T-cell derived cytokine with antitumor activity shown to be dependent on NK cells or CD8+ T cells through induction of central and effector memory cells. Two previous phase I studies suggested activity in MM. Methods: We conducted a phase II study of IL-21 evaluating the response rate (ORR) by RECIST, toxicity, progression free survival (PFS) and biomarker profile. Pts with no prior systemic therapy for MM were treated with IL-21 using 3 different dosing regimens. The initial cohort received 50 μ g/kg/day by outpatient intravenous bolus injection daily × 5, weeks 1, 3, 5 q 8 wks. Cohort 2 received 30 μ g/kg/day in the same schedule and Cohort 3 received 50 μ g/kg/day daily × 5, weeks 1, 3 q 6 wks. Results: 40 pts were enrolled: 3 in cohort 1, 30 in cohort 2, 7 in cohort 3. Two pts in cohort 1 had dose limiting toxicity (DLTs) and 4 in cohort 3, thus all other pts were treated with the 30 ug/kg/day dose. The most common adverse events were fatigue, rash, diarrhea and myalgia. 37 pts are evaluable for response: 9 had a PR (ORR = 24.3%; median duration 5 mo), 16 had stable disease (median 5.1 mo) and 12 had PD. ORR was not dependent on dose, IL-21 receptor expression or BRAF mutation status (3 of the PRs were BRAF positive, 5 were BRAF negative, 1 was BRAF inconclusive). The median PFS is 5.19 mo (95% C.I. [2.17, 5.95]). The encouraging PFS result was examined further by comparing the outcome of this study to historical NCIC CTG phase II melanoma trials in those patients who matched the IL-21 trial entry criteria (n = 68). The PFS in the historical group was 1.58 mo (95% C.I. [1.22, 1.87]). A multivariate analysis comparing PFS of IL-21 treated patients to the historical group to adjust for prognostic factors (age, gender, perf status, liver mets, number of metastatic sites) revealed that age (HR = 0.97, p = 0.0008), performance status (1 vs. 0: HR = 1.497 and 2 vs. 0: HR = 8.091, p = 0.0026) and treatment with IL-21 (HR = 0.584, p = 0.0198) were significant predictors of PFS. Conclusions: The ORR to IL-21 is 24% for first line MM and warrants further investigation. A median PFS of 5.19 months is superior to that observed in historical NCIC CTG data even when adjusted for prognostic variables. We plan a randomized phase II study of IL-21 to confirm and extend these observations. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ZymoGentics ZymoGentics ZymoGenetics
Thromboembolic events in French patients with breast and prostate cancer hospitalized in 2011 and 2012: Incidence and costs.
Authors: Florian Scotte, Isabelle Borget, Alexandre Vainchtock, Nicolas Martelli
Journal: Journal of Clinical Oncology (2014)

192 Background: Venous thromboembolic event (VTE) is a common complication for cancer patients, leading to hospitalizations that increase the burden of cancer management. We evaluated the incidence and costs of VTE-related hospitalizations for patients with breast or prostate cancer, two of the most frequent cancers in France. Methods: We used the French national hospital database (PMSI) to select new patients with BC or PC in 2010, who had at least one VTE-related hospitalization during the following two years. VTE-related stays and patients were identified using the disease-specific ICD-10 codes. Hospital costs were estimated from the healthcare system perspective and included care, treatments, accommodation/investment costs and medical/technical procedures, using the French official tariffs. Results: Among 107,916 new patients with BC or PC, 2,268 were hospitalized for a VTE, representing an overall of 2,814 admissions. VTE was classified as primary or related diagnosis (PD/RD) in 1,004 (36%) admissions. Among those PD/RD admissions, pulmonary embolism was the most frequent diagnosis as it led to 626 (62%) stays. Deep venous thrombosis was the second cause of hospitalization (248 admissions; 25% of PD/RD admissions). Re-hospitalisation for recurrence was frequent, as it occurred 546 cases (19.4%) of all VTE-related hospitalizations. For a patient who did not experience recurrence, the mean cost per patient was €3,302 and €3,611 for BC and PC patients respectively. But this amount was highly increased for patients with recurrent VTE, to €5,545 per BC patient and €5,692 per PC patient. Finally, VTE-related hospitalizations were responsible for an overall expenditure of €3.40 million over two years, including €335,000 due to recurrent events. Conclusions: In cancer patients, VTE-related hospitalizations remain frequent and induce an elevated cost. Adequate prophylaxis and management could be an efficient way to reduce the incidence of this common complication and its economic burden. [Table: see text]
Oral Contraceptive Use and Malignant Melanoma&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: C Bain, C H Hennekens, F E Speizer, B Rosner, W Willett, C Belanger
Journal: JNCI Journal of the National Cancer Institute (1982)

There was no overall relationship between a prior history of oral contraceptive (OC) use and the development of melanoma among 141 cases of nonfatal malignant melanoma and 2,820 age-matched controls drawn from respondents to a large postal survey of registered U.S. nurses; crude relative risk (RR) was 0.93 and 95% confidence limits (CL) were between 0.64 and 1.36. Adjustment for a number of additional variables did not alter this estimate materially. Duration of OC use and interval since first use were similarly unrelated to the occurrence of melanoma. For women diagnosed before age 40, there was a crude positive association of "ever" use of OC and melanoma (RR = 1.78; 95% CL, 1.11-2.86). However, adjustment for geography and other variables diminished this association and rendered it statistically not significant (RR = 1.43, 95% CL, 0.83-2.46). These data do not support the hypothesis that OC use is an independent risk factor for melanoma.