tbuckley/cabot-search huggingface dataset:
Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC)
Authors: U. Gatzemeier, A. Pluzanska, A. Szczesna, E. Kaukel, J. Roubec, U. Brennscheidt, F. De Rosa, B. Mueller, J. Von Pawel
Journal: Journal of Clinical Oncology (2004)

7010 Background: Oral erlotinib is a potent HER1/EGFR tyrosine kinase-phosphorylation inhibitor with single-agent antitumor activity and has shown additive effects when added to chemotherapy in preclinical models. TALENT was a placebo-controlled study in patients (pts) with previously untreated advanced NSCLC to receive erlotinib at 150mg/d or placebo (PBO) with 6 cycles of gemcitabine and cisplatin (GC) followed by monotherapy. The primary endpoint was duration of survival with secondary efficacy endpoints of: time to progression, response rate, duration of response (using RECIST); pharmacokinetic and pharmacodynamic parameters; quality of life (using the Lung Cancer Symptom Scale). EGFR and HER2 expression rates were also assessed. A standard safety analysis was done. Methods: Chemotherapy was given for a maximum of 6 cycles after which patients continued on study drug until disease progression (PD). Treatment with study drug beyond PD was permitted. Eligibility criteria for both parts of the study included: chemo-naive patients with unresectable stage III or IV NSCLC; age ≥18 years and ECOG PS of 0–1. Results: A total of 1172 pts were enrolled from 164 sites worldwide. The demographic and disease characteristics were well balanced across the two treatment groups. There were no statistically significant differences in overall survival (OS), time to progression (TTP) as described in the table below and quality of life (time to symptomatic progression [TSP]). The toxicity profile of erlotinib combined with GC was not significantly inferior to GC alone, with the exception of increased incidences of grade 3/4 diarrhea (<1% placebo vs. 6% erlotinib) and grade 3/4 skin rash (<1% placebo vs. 10% erlotinib). Conclusions: Erlotinib in combination with GC did not improve survival or other treatment outcomes in patients with advanced NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Lilly AstraZeneca Merck; Eli Lilly; AstraZeneca; Bristol-Myers Squibb
Role of MRI in osteosarcoma for chemotherapy response evaluation and prediction: Correlation with histological necrosis
Authors: J. Bajpai, S. Gamnagatti, V. Sreenivas, R. Phulia, M. Sharma, S. A. Khan, S. Rastogi, R. Safaya, A. Malhotra, S. Bakhshi
Journal: Journal of Clinical Oncology (2009)

10540 Background:Histologic necrosis (HN), the current gold standard for response evaluation in osteosarcoma (OS), is accessible only after neoadjuvant chemotherapy (NACT) and may get affected by confounding factors. Thus, it would be useful to have surrogate markers of response evaluation and prognostication using magnetic resonance imaging (MRI) to individualize therapy. Method:Thirty-one treatment naïve OS patients received 3 cycles of NACT followed by surgery during 2006–2008. All patients underwent baseline and post-NACT conventional(C), diffusion-weighted (DW) and dynamic contrast enhanced (DCE) MRI. Taking ‘Huvos grading’ (good response &gt;/= 90% HN) as reference standard, various parameters of MRI were compared with it. Tumor considered as ellipsoidal; volume (V), average tumor plane (ATP) and relative(r)-ATP (ATP/body surface area) were calculated using standard formula for ellipse. Receiver operating characteristic curves were generated to assess the best threshold and predictability. Sensitivity and specificity were calculated along with 95% confidence limits. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. Results: Both pre-and post NACT, absolute and relative size parameters were well correlated with HN, though post NACT change in parameters did not. Apparent diffusion coefficient (ADC), either pre-and post NACT measurements or change following chemotherapy were not correlating well. However, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter diffusion per unit volume (DV= ADC /V). Change in shape of time intensity curve did not show significant correlation. Conclusions: In OS, NACT response can be assessed and predicted by conventional and DW- MRI early in the disease course which correlates well with HN. DV seems to be a sensitive substitute for response evaluation. For DCE-MRI, more sophisticated models in future studies might be useful. [Table: see text] No significant financial relationships to disclose.
The effect of AZD0530, a highly selective, orally available Src/Abl kinase inhibitor, on biomarkers of bone resorption in healthy males
Authors: R. Eastell, R. A. Hannon, N. Gallagher, G. Clack, M. Macpherson, A. Marshall
Journal: Journal of Clinical Oncology (2005)

3041 Background: AZD0530 is a highly selective, dual-specific, orally available small molecule inhibitor of Src kinase and Bcr-Abl. Src kinase activity modulates cell proliferation, adhesion, motility and invasion and in animals its inhibition limits invasion of bone metastases and destructive bone resorption. Src kinase activity is elevated in many human tumors Methods: 2 trials in healthy, male volunteers (18–55 y) assessed the effect of AZD0530 on bone resorption, with a primary objective to establish safety and tolerability. Both were randomized, double-blind and placebo-controlled; one single ascending dose (SAD) study and one multiple ascending dose (MAD) study. The SAD study comprised 27 volunteers (cohorts of 9) who received a single 2.5–1000 mg AZD0530 dose (n=6) or placebo (n=3). In the MAD study 5 cohorts of volunteers received a single 60–250 mg dose (n=9) or placebo (n=3) then, 7–10 days later, multiple doses (10–14 d). After overnight fast, serum and second morning void urine were collected before and 24 and 48 h after the single dose (both studies) and before and 24 and 48 h after the final dose (MAD study). Markers of bone resorption measured were serum cross-linked C telopeptide of type I collagen [sCTX] and urinary cross-linked N telopeptide [NTX], expressed as a ratio to urinary creatinine. Results: In the SAD study mean levels of sCTX and uNTX/Cr significantly decreased from baseline with the 1000 mg dose. Provisional PK-PD modeling suggests the relationship between AZD0530 plasma concentrations and CTX suppression is well described by an inhibitory sigmoid E-max model. Conclusions: These findings are highly suggestive of inhibition of osteoclast-mediated bone resorption via suppression of Src kinase activity. AZD0530 may have therapeutic benefit in treating osteoclast-driven metastatic bone disease and osteoporosis as well as its potential role as an anti-invasive treatment in other cancer types. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca AstraZeneca
PC-cell derived growth factor (PCDGF/GP88): A novel circulating biomarker in breast cancer (BC) patients
Authors: G. Serrero, K. H. Tkaczuk, L. Jones, O. Goloubeva, N. S. Tait, F. S. Feldman, H. Dai
Journal: Journal of Clinical Oncology (2005)

551 Background: The identification of a measurable biomarker that is also a therapeutic target of malignant transformation or malignant progression of breast carcinoma (BC) is needed. PCDGF/GP88, an 88 kDa glycoprotein autocrine growth factor is expressed in human BC tumors in a positive correlation with their tumorigenicity. In estrogen receptor positive (ER+) cells, PCDGF/GP88 expression is low and is stimulated by estradiol whereas in ER negative cells, it is constitutively overexpressed. In ER+ cells, PCDGF/GP88 mediates estrogen mitogenic activity and its overexpression renders cells estrogen-independent and tamoxifen-resistant. Inhibition of PCDGF/GP88 expression by antisense transfection leads to inhibition of breast tumor incidence and growth in nude mice. PCDGF/GP88 is expressed in 80% of human invasive ductal carcinomas and correlates with expression of markers of poor prognosis whereas normal tissues and benign breast lesions are negative. Methods: A blood sampling study was conducted to determine the serum level of PCDGF/GP88 in healthy volunteers (HV) and BC pts. Approximately 10 ml of blood was drawn every three months and processed to obtain serum. PCDGF/GP88 serum concentration was determined in triplicate by quantitative enzyme immunoassay using human PCDGF/GP88 as standard. One hundred twenty three subjects were accrued: 16 HV and 107 BC pts. BC Patient characteristics: race, Caucasian- 51, African American-51, Asian-5; median age, 52.5 (range 29–84); stage I - 24, II - 29, III - 13, IV - 41. Results: Circulating PCDGF/GP88 was measurable in the serum. Mean level of PCDGF was 33.6 ng/ml (range 23.8–42.8) in HV and 47.4 ng/ml (range 19.9–158.4) in BC pts, (p- value= 0.004). Conclusions: PCDGF/GP88 is measurable in the sera of HV and BC pts. Comparison between the two groups of subjects indicates that PCDGF/GP88 level is significantly higher in the sera of BC pts. Future studies will examine the correlation of PCDGF/GP88 level with BC prognostic factors such as stage, tumor size, lymph node involvement, tumor grade and presence of ER and HER-2neu. We will also attempt to correlate the serum level of PCDGF/GP88 with median survival of BC pts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration A&G A&G
Aerosol inhalers
Authors: I. Hill-Smith
Journal: BMJ (1990)

Conductive education, an educational approach devised by Andras Petö in Hungary after the second world war, has attracted considerable media attention. Eight Northern Ireland families who recently had treatment for their disabled child at the Petö Institute in Budapest were identified. Six families returned postal questionnaires designed to look at parental experience of conductive education. An improvement in existing local services, as opposed to the wholesale introduction of this facility was the commonest parental hope for future provision for physically handicapped children.
Daily oral topotecan: Utilization of a metronomic dosing schedule to treat recurrent or persistent solid tumors
Authors: T. D. Tillmanns, R. Buller, C. F. Stewart, J. MacEachern, P. Schaiquevich, M. S. Walker, E. J. Stepanski
Journal: Journal of Clinical Oncology (2008)

2571 Background: Topotecan has antiangiogenic properties when administered on a metronomic schedule. This study investigated the safety, efficacy, and pharmacokinetics of oral topotecan, utilizing continuous low dose daily therapy without drug free intervals. Methods: This phase I, single-center, open-label, dose-ranging study consisted of 30-day treatment cycles of daily oral topotecan at dose levels of 0.25, 0.50, 0.75, 1.00, and 1.25 mg. Because our intent was to administer a continuous daily dose, the dose-limiting toxicity (DLT) was defined as a grade 2 adverse event. At least 3 patients (pts) were enrolled at each dose level. If 1 of 3 pts treated at a given dose level experienced a DLT, the level was expanded to 6 pts. If more than 2 of 6 pts had a DLT at that dose level, the previous dose level was considered the MTD. Results: 16 heavily pretreated pts with various solid tumors were enrolled, with an average of 4 prior regimens (range 2–11). Mean cycles received on protocol were 2 (range 1–6). 3 pts were enrolled at the 0.25 mg dose, 4 at 0.5 mg (one withdrew consent), 3 at 0.75 mg, 4 at 1.0 mg (one withdrew after new biliary obstruction secondary to rapid tumor growth), and 2 at 1.25 mg. The topotecan Cmax increased linearly with dose and the median (range) Tmax was 2 h (1–7). The DLT was reached at 1.25 mg (2 pts had Gr.3 GI toxicities). 2 pts (14% response) had stable disease (1 pt with a minor response and 1 pt with cervical cancer has stable disease for 7 months on therapy after multiple recurrences on prior regimens). The remaining pts had disease progression. The MTD for phase II evaluation was defined at 1.0 mg daily. Pending thrombospondin levels and circulating endothelial obtained on study patients may elucidate the most beneficial daily dose. Conclusions: This is the first phase I trial utilizing a continuous daily dosing of oral topotecan in this metronomic fashion. This 28-day cycle was well tolerated at a MTD dose of 1 mg orally daily. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Abstract 1453: Methods for developing patient derived xenografts in athymic nude mice
Authors: Laura A. Marlow, James L. Miller, Brandy Edenfield, Adam C. Mathias, Louis K. Dawson, William F. Durham, Robert J. Mullin, Daniel L. Small, Aidan J. Synnott, Kevin Wu, John A. Copland
Journal: Cancer Research (2015)

Abstract Patient derived xenografts (PDX) mouse models for many types of cancer have been developed recapitulating therapeutic responses in the patient for which the PDX model was derived. Essentially, live surgically resected or biopsy tumor tissues are directly implanted into immune incompetent mice to develop in vivo models to test therapies, follow tumor progression (gene mutations that occur with patient tumor progression do so in mice) or to better understand drug resistance. However, the use of PDX models also has its limitations and challenges. Our laboratory has attempted to develop PDX models in athymic nude mice for numerous cancer histotypes such as bladder, brain, breast, colon, kidney, lung, melanoma, ovarian, pancreas, sarcoma and thyroid. While melanoma and colon cancers have very high tumor take rates (73 - 100%), the other cancer histotypes do not (14 - 50%). We share our experience for each cancer histotype and the techniques used to enhance the success rates in athymic nude mice. We also address the other challenges that include expansion of tumors after cryopreservation and conversion of human tumors to mouse tumors and spontaneous lymphomas. We provide methods to test for human versus mouse content that include QPCR and immunohistochemistry Citation Format: Laura A. Marlow, James L. Miller, Brandy Edenfield, Adam C. Mathias, Louis K. Dawson, William F. Durham, Robert J. Mullin, Daniel L. Small, Aidan J. Synnott, Kevin Wu, John A. Copland. Methods for developing patient derived xenografts in athymic nude mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1453. doi:10.1158/1538-7445.AM2015-1453
Capecitabine and irinotecan (XELIRI) in first-line treatment of metastatic colorectal cancer (mCRC): A systematic review of controlled clinical trials
Authors: S. Sukumaran, N. Pavlakis, K. B. Pittman, K. Patterson, T. J. Price
Journal: Journal of Clinical Oncology (2009)

e15100 Background: Irinotecan and 5-Fluorouracil based combination is an effective regimen for mCRC. Capecitabine, an oral fluoropyrimidine, is a convenient alternative to intravenous 5- Fluorouracil. This study aims to systematically review all published and unpublished controlled phase II and III trials of XELIRI combination, used in first line treatment of mCRC, reported from 2000–2008, to describe its efficacy and safety. Methods: A literature search of MEDLINE, EMBASE, CINAHL and proceedings from ASCO, ESMO and WGIC was conducted. The primary end point was response rate (RR), secondary endpoints include: time to progression (TTP), overall survival (OS) and toxicity. Results: Thirty non-randomised phase II trials (n = 1380) along with 6 randomised phase II and 3 phase III trials, were included (pooled n = 1478). The daily dose of capecitabine ranged from 1,800 mg/m2 to 2,500 mg/m2 for 7 to 14 days per cycle and the dose of irinotecan varied from 180mg/m2 to 350 mg/m2, over a 3 week period per cycle. Amongst the non-randomised studies, the median patient age was 61 years (53–72).The median RR was 46.75% (25–78%). The median reported TTP was 7.9 months (mo) (5- 9.9 mo) and the median OS was 15.6 months (7–24.8 mo). Grade 3–4 toxicity incidence was: diarrhoea (21.5%), neutropenia (12%), vomiting (12.5%), fatigue (6%) and Hand-foot syndrome (6%). The pooled incidence of febrile neutropenia was 2.5%. Amongst the randomised trials, the comparator regimens were XELOX or FOLFIRI. Median age was 65 years (61–74). RR for XELIRI was 39% (34–56%) compared to 47% (27–61.8%) for the non XELIRI comparator arms. Median reported TTP was 8.2 mo (5.7–12.5 mo) for the XELIRI arms and 9.2 mo for the comparator arms. Conclusions: XELIRI is an effective and feasible regime in the first line management of mCRC. However the optimal role of this combination remains to be established. No significant financial relationships to disclose.
High blood pressure is the leading health risk factor in India, finds study
Authors: Cheryl Travasso
Journal: BMJ (2015)

<i>Agrobacterium vitis</i>, the primary cause of grape crown gall disease, is known to survive internally in grapevines and to spread in propagation material. In this study, we showed that the bacterium can be detected in dormant grape buds and on surfaces of leaves collected from commercial vineyards. Using a highly selective and sensitive method based on magnetic capture hybridization (MCH) together with real-time PCR, we detected <i>A. vitis</i> in as much as 90% of dormant bud samples and in up to 40% of leaf samples from individual vineyards. The highest percentages of detection occurred in samples collected from vineyards with high incidences of crown gall. <i>A. vitis</i> was also detected in 22% of wild grapevines (<i>Vitis riparia</i>) collected in New York and in 25% of feral grapevines that included <i>V</i>. <i>californica</i> in California. Several of these vines were growing more than 2 km from commercial vineyards, demonstrating that wild grapevines can serve as a significant inoculum reservoir. The specificity of the MCH and real-time PCR assay used to detect tumorigenic <i>A. vitis</i> in the environment was further demonstrated by the finding that 69 nontumorigenic strains from regions across the United States did not amplify a <i>virD2</i> PCR product.
Sensitivity of computer-aided diagnosis among participants at one center in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO)
Authors: M. M. Oken, T. R. Church, S. Inampudi, S. C. Oancea, G. D. Watt, M. Plunkett, G. Marquez
Journal: Journal of Clinical Oncology (2008)

1546 Background: Report of a pilot study to determine if computer-aided diagnosis (CAD) for detection of lung cancers on chest x-ray (CXR) can improve sensitivity for early detection. Methods: All screening CXR, representing up to 4 annual screens from the 126 subjects at the Minnesota PLCO Screening Center diagnosed with lung cancer, were evaluated. A radiologist read the films in a blinded fashion before and while using the CAD program. For all CXR films, the radiologist recorded radiograph location and suspicion level for regions of interest (ROI) prior to seeing the CAD results and subsequently for ROI indicated by the CAD program. The likely location in the lung was also recorded along with the radiologist's quantitative confidence level. ROI were matched with actual cancer diagnostic records to determine if cancer could have been identified by CAD. Results: Of the 63 lung cancers discovered within 6 months of a screening CXR, 34 were potentially identified by CAD, for a raw sensitivity of 54%. Only 9 of the 63 cancers were not screen detected and 3 of those were associated with a CAD region of interest. Of the 66 cancers that had a first CXR at least 30 months prior to diagnosis, 7 were potentially identified by CAD at that CXR; 5 of the 7 were stage III or IV. 72 of the 126 lung cancers were stage III or IV at diagnosis. Of these, 7 were potentially diagnosed 18 months earlier by CAD-enhanced CXR. Conclusions: This pilot study indicates the potential for CAD to detect some lung cancers 30 months or more earlier than CXR alone, possibly diagnosing the case at a more favorable stage. No significant financial relationships to disclose.
Phase I/II dose-escalation trial of patupilone every 3 weeks in patients with relapsed/refractory ovarian cancer
Authors: W. M. Smit, J. Šufliarsky, S. Spanik, M. Wagnerová, S. Kaye, A. M. Oza, M. Gore, K. Williams, A. Johri, W. W. Ten Bokkel Huinink
Journal: Journal of Clinical Oncology (2005)

5056 Background: Pts with newly diagnosed advanced ovarian cancer generally receive platinum plus taxane therapy. For pts who do not respond or relapse within 6 months, outlook remains poor. Patupilone, a natural epothilone, is a microtubule-targeting cytotoxic that has demonstrated clinical activity in taxane-sensitive and -resistant tumors. In a phase I/II study, we are investigating the safety and efficacy of patupilone in pts with advanced ovarian cancer who had failed to respond to or had relapsed within 6 months of first-line platinum therapy. Methods: Pts receive patupilone at a starting dose of 6.5 mg/m2 via 10- to 20-min IV infusion once every 3 wk (q3w) with proactive diarrhea management. Results: To date, 31 pts have been enrolled in 9 cohorts receiving 6.5 (n = 3), 7.0 (n = 3), 7.5 (n = 3), 8.0 (n = 6), 8.5 (n = 3), 9.0 (n = 6), 9.5 (n = 3), 10.0 (n = 3), and 10.5 (n = 1) mg/m2 patupilone. Currently, 29 pts are eligible for assessment; 90% had received prior taxane therapy. DLTs were not reported until the 8.0- and 8.5-mg/m2 cohorts; 1 pt in each had grade (gr) 3 fatigue. Gr 4 serum uric acid, gr 3 hypomagnesemia, and gr 2 serum creatinine precipitated by surgical ileus were reported on day 21 of the first cycle by a pt enrolled in the 9.0-mg/m2 cohort. However, these toxicities were deemed unrelated to study drug, the cohort was expanded and no DLTs were reported. Dose escalation has continued to the ongoing 10.5-mg/m2 cohort. Gr 3 diarrhea, gr 3/4 fatigue/malaise, and gr 3 vomiting were reported in 17%, 14%, and 7% of pts, respectively. Eight (28%) pts had gr 1/2 neuropathy/paresthesia; 1 case became gr 3 in a heavily (19 platinum cycles) pretreated pt. Hematologic toxicity was uncommon and 3 pts had gr 1 alopecia. Of the 19 pts evaluable for tumor response by RECIST, 1 had CR, 1 had PR, and 7 had SD; 1 additional pt had CR based on ascites disappearance. Of the 24 pts who had increased CA-125 at baseline, 7 (29%) had a 50% reduction in CA-125 levels (2 confirmed, 5 unconfirmed). Conclusions: Preliminary data indicate that patupilone administered once q3w is safe and well tolerated. The MTD has not been reached; dose escalation continues. Preliminary antitumor response is promising in this previously treated platinum-resistant pt population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Novartis Pharmaceuticals AG Novartis Novartis Novartis