tbuckley/cabot-search huggingface dataset:
Ancestim (r-metHuSCF) in combination with filgrastim to rescue mobilization and collection of peripheral blood progenitor cells for autologous transplantation. Compassionate use in 288 patients at 62 sites in France (1998–2003)
Authors: J.-F. Rossi, K. Safsafi, P. Royce, J. Caraux, K. Safsafik
Journal: Journal of Clinical Oncology (2004)

6642 Background: Approximately 15% of patients (pts) eligible for HDC and peripheral blood progenitor cell (PBPC) transplantation, failed to generate an adequate PBPC graft. Methods: Ancestim (r-metHuSCF, Amgen, Thousand Oaks, CA) was delivered on a named-pt basis under the French Temporary Authorization for Use program to 288 pts with prior failure to achieve 20 CD34+ cells/μL peripheral blood (no leukapheresis attempt, n = 209 pts) or failure to collect an adequate PBPC yield (2x106 CD34+ cells/kg; n = 64 pts) (no. of prior failed attempts: 1 to 5)(median age 53 yrs [1 –70 yrs], n ≤ 18 yrs of age = 31) (lymphomas, 140 pts; myeloma, 84 pts; CLL, 21 pts; Ewing's sarcoma, 12 pts; neuroblastomas, 11 pts; other tumor types: 20 pts). Ancestim (20μg/kg/d) was combined with filgrastim alone (10μg/kg/d; median 7 d, 151 pts) or with chemotherapy and filgrastim (5μg/kg/d, median 12 d, 136 pts). Results: An autograft appropriate to support HDC (2x106 CD34+ cells/kg) was obtained from 106 (37%) of 288 pts after rescue with ancestim (72 of 209 pts with prior failure(s) to mobilize CD34+ cells to the peripheral blood; 29 of 64 pts with prior failure(s) of collection of an adequate CD34+ cell yield). In the 134 pts to undergo leukaphereses after the ancestim attempt, the median (range) CD34+ cell yield was 2.77 (0.03 to 39.05) x 106 cells/kg. To date, 85 pts have undergone transplantation. Hematological recovery was comparable to those obtained with filgrastim-mobilized PBPCs (platelets > 20 x 109/L : median 13 d; neutrophils > 0.5 109/L : median : 12 d). Only 2 pts have experienced anaphylactoid symptoms associated with systemic histamine release after inadvertent IV injection. Conclusions: The combination of ancestim and filgrastim allows to rescue an important number of pts who experienced prior failure of PBPC mobilization and/or collection, without any significant toxicity in this large multicenter series. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen France; Amgen UK Amgen, Inc.
Prophylaxis of recurrent chemotherapy-induced oral mucositis: A phase II multicenter, randomized, placebo-controlled trial of recombinant human intestinal trefoil factor (rhITF)
Authors: N. P. Barker, D. E. Peterson, L. I. Akhmadullina, I. Rodionova, N. Z. Sherman, J. M. Gertner, C. Woon
Journal: Journal of Clinical Oncology (2008)

9514 Background: Naturally occurring ITF is a peptide produced predominantly in the gastrointestinal tract, where it plays a key role in mucosal restitution. The purpose of the current Phase II study was to evaluate safety and efficacy of rhITF administered as an oral spray topically to the oral cavity of patients at high risk for developing oral mucositis (OM). Methods: Colorectal cancer patients (N=99) presenting with symptomatic OM (WHO grade ≥2) in the first cycle of chemotherapy were randomized into three groups (N=33/group) and treated with either placebo, rhITF 10mg/mL (low dose) or rhITF 80mg/mL (high dose) by oral spray (300μl, 8 times/day) for 14 consecutive days in the second chemotherapy cycle. Patients were assessed days 1, 3, 5, 7, 10, 12, 14 and 21 ± 2 for WHO grade of OM, and treatment-related effects. Results: Patient-reported compliance was >95%. rhITF oral spray was well tolerated. Treatment groups were not significantly different with respect to the development of Treatment-Emergent Signs and Symptoms (TESSs). A minority of chemotherapy patients (6/99, 6.1%) had TESSs; 4 were associated with treatment (1 placebo, 2 low dose and 1 high dose rhITF respectively). All events were mild to moderate in intensity and resolved spontaneously without sequelae. There were no serious adverse events or deaths in the study. Frequency of WHO grade ≥2 oral mucositis in the placebo, low dose rhITF and high dose rhITF groups was 48.5% (16/33), 9.1% (3/33) and 12.1% (4/33), respectively (for either low or high dose versus placebo p<0.001). Assessment of area under the curve relative to OM incidence and severity revealed a statistically significant treatment effect of rhITF versus placebo (WHO scores, p<0.01). Conclusions: rhITF oral spray formulation appears safe and well-tolerated when given concurrently with chemotherapy. Prophylactic use of rhITF at either high or low dose was associated with a significant (∼80%) reduction in OM occurrence in patients at high risk for development of the lesion. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration The GI Company Inc. ActoGenix NV, Alizyme Ther., Ltd., Endo Pharm Inc.,, Genzyme Corporation, MGI Pharma Inc., The GI Company Inc. The GI Company Inc. The GI Company Inc.
Change in the manifestations of asthma and asthma-related traits in childhood: a latent transition analysis
Authors: Frances L. Garden, Judy M. Simpson, Craig M. Mellis, Guy B. Marks
Journal: European Respiratory Journal (2015)

It is known that asthma is a heterogeneous entity whose manifestations vary with age. Our objective was to examine changes in the manifestation of asthma and asthma-related traits in childhood by defining empirically derived childhood asthma phenotypes and examining their transitions over time. To define the phenotypes we used data on respiratory symptoms, healthcare utilisation, medications, spirometry, airway hyperresponsiveness (AHR), exhaled nitric oxide concentration and atopy from a birth cohort recruited on the basis of having a first-degree relative with asthma. Data were acquired at ages 1.5–11.5 years and analysed using latent transition analysis. In a study population of 370 participants, we classified subjects into four phenotypes: 1) nonatopic, few symptoms (prevalence range from 1.5 to 5 years: 52–60%), 2) atopic, few symptoms (3–21%), 3) nonatopic, asthma and rhinitis symptoms (13–35%), and 4) atopic, asthma and rhinitis symptoms (2–14%) in early childhood; and 1) nonatopic, no respiratory disease (prevalence range from 8 to 11.5 years: 41–46%), 2) atopic, no respiratory disease (23–33%), 3) nonatopic, asthma symptoms, no AHR or airway inflammation (8–12%) and 4) atopic asthma (19%) in mid-childhood. Transitioning between phenotypes was common in early childhood, but less common in later childhood. This analysis represents the first attempt to incorporate longitudinal patterns of several manifestations of asthma into a single model to simultaneously define phenotypes and examine their transitions over time. It provides quantitative support for the view that asthma is a heterogeneous entity, and that some children with wheeze and other respiratory symptoms in early life progress to asthma in mid-childhood, while others become asymptomatic.
Peripheral T cell lymphoma.
Authors: R Liang, D Todd, T K Chan, K L Wong, F Ho, S L Loke
Journal: Journal of Clinical Oncology (1987)

Thirty-one Chinese patients with peripheral T cell lymphoma (PTCL) were reviewed. Using the modified Japanese Lymphoma Group classification, there were nine (29%) of the pleomorphic type, 16 (52%) immunoblastic lymphadenopathy (IBL)-like, two (7%) T-zone lymphoma, and one (3%) Lennert's lymphoepithelioid type. Three (9%) were not classifiable. All were positive for T11 (E rosette receptor antigen). Fifty-four percent (15 of 28) were positive predominantly for T4 (helper T cell) and 46% (13/28) for T8 (suppressor T cell). The median age of the patients was 57 years. They usually presented with advanced disease, and while extranodal involvement was common, CNS disease was not seen. The IBL-like type was associated with a positive Coombs' test and polyclonal hypergammaglobulinemia. Five of the nine pleomorphic type were checked for antibody to HTLV-I virus and all were negative. PTCL was associated with poor prognosis, which was not influenced by the histologic subtypes and the T4/T8 phenotypes. The complete response rate of 13 consecutive patients who received the BACOP (bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisone) L17M regimen was significantly better than the 16 historic controls who received other less-intensive regiments, 84% v 19% (P less than .01). The relapse rate was also significantly lower, 9% v 100% (P less than .001). There appeared to be an improvement in the disease-free survival (DFS) (80% v 0% at 18 months), as well as the overall survival (60% v 36% at 18 months), but the differences did not reach statistical significance due to small sample sizes.
Phase II trial of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme
Authors: A. Lai, P. Nghiemphu, R. Green, L. Spier, S. Peak, S. Phuphanich, L. Fehrenbacher, T. Kolevska, J. Polikoff, T. Cloughesy
Journal: Journal of Clinical Oncology (2009)

2000 Background: Bevacizumab (BV) is a humanized monoclonal antibody directed against the vascular endothelial growth factor (VEGF). Based on the promising activity of BV in the treatment of recurrent glioblastoma, we are conducting a phase II trial to determine whether up-front treatment of newly diagnosed GBM with BV may be more advantageous than withholding BV until recurrence. In this trial, we evaluate the safety and efficacy of BV combined with standard of care radiation (RT) and temozolomide (TMZ) and radiation (RT) for newly-diagnosed GBM. Methods: This is a phase II trial with a 10-patient pilot and 60-patient expansion phases. Newly-diagnosed GBM patients with no prior treatments are eligible. Primary outcome measure is overall survival; the secondary outcome measure is TTP and 12-month survival. Therapy began between 3–5 weeks of surgery with BV (10 mg/kg every 2 weeks), TMZ (75 mg/m2 daily), and external beam RT (30 x 200 Gy) on the same day. After completion of radiation, patients are then placed on a maintenance phase of BV (10mg/kg every 2 weeks) and TMZ (150–200 mg/m 2 5 out of every 28 days) until progression or 24 months in which patients are then maintained on BV only. Results: 70 of 70 projected GBM patients have been enrolled between August 2006 and November 2008 at UCLA and Kaiser Permanente (KP) (Northern and Southern California). All patients had resections to ensure that frozen tissue (&gt;200mg) was collected. The median age was 57.4 years (range 31–75). MGMT methylation analysis has been performed on 52/70 patients with ∼40% showing methylation. Severe adverse events to date have included ischemic stroke, pulmonary embolus, wound breakdown, GI bleeding/perforation, and renal dysfunction. Isolated cases of retinal detachment and optic neuropathy have also been observed. As of now, 35/70 patients are off study (26 due to progression and 9 due to SAE). Preliminary TTP by Kaplan-Meier analysis is promising compared to that of a UCLA/KP control group of patients that received the conventional RT/TMZ regimen. Conclusions: Addition of BV to the standard regimen of TMZ and RT for newly-diagnosed GBM is well-tolerated and shows promising efficacy. More detailed analysis of safety and efficacy will presented. [Table: see text]
90 hour continuous intravenous busulfan infusion: PK and test dose predictability in allogenic bone marrow transplantation patients
Authors: C. M. Walko, C. M. Lindley, J. Collins, C. Krasnov, R. D. Harvey, D. A. Gabriel, J. Serody, T. Comeau, T. C. Shea
Journal: Journal of Clinical Oncology (2005)

6652 Background: Precise and predictable dosing of busulfan is important in pre-transplant conditioning regimens because the AUC of high dose busulfan (HD-Bu) has been correlated with toxicity, engraftment and relapse. Use of a continuous infusion, rather than traditional bolus dosing, would theoretically produce a target busulfan concentration within the desired range throughout the four-day interval. This consistency in concentration may be associated with superior safety and efficacy. The objective of this study is to evaluate the ability of a test dose to predict steady state systemic exposure of a continuous 90 hour infusion of HD-Bu. Methods: The day prior to HD-Bu, seven patients received a single test dose of intravenous busulfan (0.8 mg/kg) by two hour infusion with blood concentrations obtained at 0, 2, 4, 6, and 8 hours. Busulfan 12 mg/kg continuous infusion over 90 hours was then administered and blood samples were collected at 0, 6, 12, 18, 24, 36, 48, 60, 72, 84, 90, 92 and 96 hours. Serum concentrations were analyzed using GC-MS and noncompartmental pharmacokinetic analysis to determine clearance was performed using WIN-NONLIN. The systemic clearance (dose/AUC) of the test dose was compared with the continuous infusion. Results: Mean (range) clearance for the test and continuous infusion was 18238 mL/hr (10444 33884) and 18128 mL/hr (10004 32491), respectively. Bias and precision for the test dose compared with the continuous infusion were 0.6% and 9%, respectively. Conclusions: These data suggest the systemic clearance determined from a busulfan test dose may be used to target therapeutic AUC of a 90 hour continuous infusion. No significant financial relationships to disclose.
EphA3 As a Molecular Target In Multiple Myeloma: Opportunity For a Novel Therapeutic Approach With a Specific Monoclonal Antibody
Authors: Antonella Caivano, Francesco La Rocca, Ilaria Laurenzana, Alessandra Favole, Irma Airoldi, Emma Di Carlo, Valentina Gaidano, Enrico Bracco, Oreste Villani, Giuseppe Pietrantuono, Luciana De Luca, Annalisa Morano, Vittorio Simeon, Stefania Trino, Simona Berardi, Antonio Basile, Martin Lackmann, Angelo Vacca, Pellegrino Musto, Francesco Frassoni, Daniela Cilloni
Journal: Blood (2013)
<i>BRCA1</i>and<i>BRCA2</i>Mutation Testing in Young Women With Breast Cancer
Authors: Shoshana M. Rosenberg, Kathryn J. Ruddy, Rulla M. Tamimi, Shari Gelber, Lidia Schapira, Steven Come, Virginia F. Borges, Bryce Larsen, Judy E. Garber, Ann H. Partridge
Journal: JAMA Oncology (2016)

BRCA testing is recommended for young women diagnosed as having breast cancer, but little is known about decisions surrounding testing and how results may influence treatment decisions in young patients.To describe the use of BRCA testing and to evaluate how concerns about genetic risk and use of genetic information affect subsequent treatment decisions in young women with breast cancer.Cross-sectional analysis of data collected following the opening of the study to accrual from October 10, 2006, through December 31, 2014, as part of the Helping Ourselves, Helping Others: Young Women's Breast Cancer Study, an ongoing prospective cohort study. Study participants included 897 women aged 40 years and younger at breast cancer diagnosis from 11 academic and community medical centers.Frequency and trends in the use of BRCA testing and how genetic information is used to make treatment decisions among women who test positive vs negative for a BRCA mutation.A total of 780 (87.0%) of 897 women reported BRCA testing by 1 year after breast cancer diagnosis (mean age at diagnosis, 35.3 vs 36.9 years for untested women; P < .001), with the frequency of testing increasing among women diagnosed from August 1, 2006, through December 31, 2013. Of 39 women who were diagnosed as having breast cancer in 2006, 30 (76.9%) reported testing. In 2007, a slightly lower percentage of women (87 of 124 [70.2%]) reported testing; however, the proportion tested increased each subsequent year, with 141 (96.6%) of 146 and 123 (95.3%) of 129 women diagnosed as having breast cancer in 2012 and 2013, respectively, reporting BRCA testing (P < .001). Among untested women, 37 (31.6%) of 117 did not report discussion of the possibility that they might have a mutation with a physician and/or genetic counselor, and 43 (36.8%) of 117 were thinking of testing in the future. A total of 248 (29.8%) of 831 women said that knowledge or concern about genetic risk influenced treatment decisions; among these women, 76 (86.4%) of 88 mutation carriers and 82 (51.2%) of 160 noncarriers chose bilateral mastectomy (P < .001). Fewer women reported that systemic treatment decisions were influenced by genetic risk concern.Rates of BRCA1 and BRCA2 mutation testing are increasing in young women with breast cancer. Given that knowledge and concern about genetic risk influence surgical decisions and may affect systemic therapy trial eligibility, all young women with breast cancer should be counseled and offered genetic testing, consistent with the National Comprehensive Cancer Network guidelines.
Ability of bone mineral density to predict osteoporotic fractures
Authors: K. Brooks, R. Shakespeare, P. Christmas, R. Whatley, D. Jenkins, C. Woodward, A. Mortimore
Journal: BMJ (1996)

# Conclusion of meta-analysis was unjustified {#article-title-2} EDITOR,—We believe that the “critical appraisal skills for purchasers” approach1 2 has greatly improved our ability to evaluate published papers. We recently considered Deborah Marshall and colleagues' meta-analysis of how well measures of bone mineral density predict the occurrence of osteoporotic fractures.3 We asked ourselves: Does this paper show whether screening by measuring bone mineral density would be a useful approach to reducing osteoporotic fractures in our population? Our principal conclusions were as follows:
α1-Blockers Improve Benign Prostatic Obstruction in Men with Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis of Urodynamic Studies
Authors: Ferdinando Fusco, Alessandro Palmieri, Vincenzo Ficarra, Gianluca Giannarini, Giacomo Novara, Nicola Longo, Paolo Verze, Massimiliano Creta, Vincenzo Mirone
Journal: European Urology (2016)
Clinical activity of GW572016 in EGF10003 in patients with solid tumors
Authors: M. Versola, H. A. Burris, S. Jones, G. Wilding, C. Taylor, L. Pandite, D. A. Smith, A. Stead, N. L. Spector
Journal: Journal of Clinical Oncology (2004)

3047 Background. ErbB1 or ErbB2 overexpression predicts for a poor clinical outcome in certain epithelial malignancies. GW572016, a reversible inhibitor of ErbB1/ErbB2 tyrosine kinases, induces tumor cell growth arrest and/or apoptosis. Methods. 64 patients (pts) (22 colon, 6 lung, 5 adenocarcinoma of unknown primary (AUP), 5 H&N, 5 renal, 4 breast, 3 ovarian, and 14 other) were treated with GW572016 once (qd) or twice (bid) daily in a dose escalation scheme. Thirty-nine pts were administered 175-1800 mg qd and 25 pts administered either 500, 750, or 900 mg bid. Pts were evaluated monthly and treated until disease progression or intolerable side effects. Clinical response was determined every 8 wks (RECIST). Results. One CR (sustained for 16+ mos) was observed in an ErbB1 overexpressing head and neck squamous cell carcinoma. Twenty-two pts with various tumors, most overexpressing either ErbB1 or ErbB2, experienced SD with a median duration of 4 mos (range 1–13+ months). Patients continuing therapy for > 4 mos were administered GW572016 at doses ≥ 1200 mg/day. Of the 22 SD pts, 2 with non-small cell lung cancer and AUP metastatic to lung, both progressing on previous Iressa therapy, remained on GW572016 for 12+ and 8+ mos, respectively. Transient grade 1–2 rash, diarrhea, nausea/vomiting, fatigue, and anorexia were the most frequent AEs in all cohorts. There were no cases of interstitial pneumonitis. We also investigated whether serum VEGF levels represent an easily accessible pharmacodynamic endpoint for GW572016 therapy since VEGF is regulated in part by ErbB receptor signaling. Days 0 and 14 serum VEGF levels were assessed with VEGF inhibition observed in 30 patients (median % inhibition-23%). Conclusion.QD administration of GW572016 is well tolerated with evidence of clinical activity in this heavily pre-treated population. Serum VEGF may be a potential biomarker for GW572016 activity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline Bristol-Myers Squibb; GlaxoSmithKline GlaxoSmithKline
Procollagen-I-propeptide and β-crosslaps are prognostic markers for pretherapeutic estimation of treatment success of combined radio- and bisphosphonate therapy in patients with bone metastases—A phase-II study
Authors: W. Wagner, A. Radmard, M. Bach, C. Loitsch, M. G. Krukemeyer, G. J. Wiedemann
Journal: Journal of Clinical Oncology (2007)

9096 Background: Multiple painful bone metastases are a common problem in patients suffering from breast and prostate cancer. Side effects of morphines can impair quality of life. Pain reduction can also be achieved by radiotherapy combined with bisphosphonates; however, this treatment is not successful in all patients. Methods: 35 patients with breast and prostate cancer suffering from painful bone metastases (multiple metastases in 29 cases, solitary metastasis in 6 cases: were locally irradiated (30 - 40 Gy over 3 - 4 weeks, conventional dose fractionation). In addition they received a bisphosphonate therapy (zoledronate). Before and after radiotherapy procollagen-I- propeptide and β-crosslaps were measured as parameters for the intensity of bone metabolism. Results: 24 patients experienced complete pain relief, 10 patients partial pain relief and one patient noticed no effect of treatment. The values of procollagen-I-propeptide (normal range 19–102 μg/l) and β-crosslaps (normal range &lt;= 1,0 μg/l) were correlated with treatment success. At pretherapeutical procollagen-I- propeptide levels above 190 μg/l, all patients became entirely free of pain. All patients with β-crosslaps values above 0.5 μg/l became equally free of pain, irrespective of the number of metastases and tumour entity. The mean levels of procollagen-I-propeptide as well as β-crosslaps correlate directly and without exception with analgesia, reduction of pain or persistency of pain as final results. No correlation concerning the values was found before and after therapy. Conclusion: Procollagen-I-propeptide as well as β-crosslaps measurements before the beginning of a radio- and bisphosphonate therapy due to painful bone metastases are an excellent prognostic parameter to predict the success of therapy. Where high initial values (procollagen-I-propeptide &gt; 190 μg/l or β-crosslaps &gt; 0.5 μg/l) were measured, complete analgesia was achieved through therapy. Despite this clinically clear statement, a statistical significance with a t-Test was not evaluable at the current collection of patient data. Therefore, 20 more patients were examined; the results are yet to come. No significant financial relationships to disclose.