tbuckley/cabot-search huggingface dataset:
Phase II study of oxaliplatin (OX), 5-fluorouracil (5-FU), and radiation therapy (RT) followed by gemcitabine (GEM) in patients with unresectable pancreatic cancer
Authors: G. P. Kim, M. Haddock, N. R. Foster, J. Bollinger, P. J. Stella, J. W. Kugler, S. R. Alberts, J. Martenson
Journal: Journal of Clinical Oncology (2008)

15553 Background: Synergistic cytotoxicity with combinations of OX and 5-FU have been observed in a number of tumor systems. Both drugs have known radiosensitizing properties. This phase II study was conducted to evaluate the efficacy of concomitant 5-FU, OX and RT followed by GEM in patients (pts) with unresectable pancreatic cancer. Methods: Pts with unresectable non-metastatic invasive ductal pancreatic cancer with ECOG performance status of 0–1 were eligible. Surgical staging was not required. Pts received continuous infusion 5-FU 180 mg/m2 throughout RT and OX 85 mg/m2 on days 1, 15, 29 of RT by intravenous infusion. RT consisted of 45 Gy to the tumor and regional nodes followed by a 5.4 Gy boost to the gross tumor using conformal techniques and 1.8 Gy fractions. Upon completion of RT, patients received weekly GEM 1,000 mg/m2, two weeks out of three for 4 cycles. The primary endpoint was survival (OS) at one year with secondary endpoints of median survival, time to progression (TTP) and toxicity. Results: 53 eligible pts were enrolled in 14 mos. M:F- 30:23 with a median age of 65 (range: 31- 80). Median follow-up is 21.6 months (range: 14.3 - 29.7), with 9 pts still alive. The confirmed response rate is 6% (3 PR, 0 CR). Median TTP 7.1 mos (95% CI: 4.9–9.0), 12-month survival 34% (95% CI: 20–63%) and median survival 9.3 mos (95% CI: 5.9–11.4) were observed. Fifty (94%) and 10 (19%) pts experienced at least one grade 3+ or grade 4+ AE, respectively, with 1 pt (2%) death due to a cardiovascular event possibly related to protocol therapy. Frequently occurring maximum grade 3/4 AEs (regardless of attribution) are shown in the Table below: Conclusions: These results do not suggest an efficacy benefit for this combined modality therapy regimen. Toxicity results are similar to those seen with other regimens. Future studies will focus on the addition of novel agents in addition to RT in this setting. Type Grade 3 % Grade 4 % Type Grade 3% Grade 4% Leukopenia 26% 2% Hypokalemia 9% 2% Neutropenia 25% 2% Nausea 28% 0% Upper GI Hemorrhage 0% 4% Vasc Access Complications 0% 4% Vomiting 17% 0% Fatigue 36% 2% Hyperglycemia 9% 2% Anorexia 28% 0% Bilirubin 11% 2% Hypotension 4% 2% Dehydration 9% 2% Diarrhea 21% 0% Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis
Abstract 11085: Testing the Life Context Model of Self-Care and Outcomes in Heart Failure: The Role of Psychosocial and Aging Factors
Authors: Debra K Moser, Kathleen Dracup, Michele M Pelter, Terry A Lennie, Gia Mudd-Martin, Martha J Biddle, John Watkins
Journal: Circulation (2013)

Most of the cost of heart failure (HF) care is due to hospitalizations, most of which can be traced to failed self-care. Factors leading to poor self-care and affecting relationships among patient ...
Bone scan “flare” in patients receiving abiraterone acetate (AA) for metastatic castration resistant prostate cancer (mCRPC): Analysis of data from a phase II study of the Department of Defense Prostate Cancer Clinical Trials Consortium.
Authors: S. K. Shah, C. J. Ryan, C. Kilian, A. Hubbell, T. S. Kheoh, C. M. Haqq, A. Molina, E. J. Small
Journal: Journal of Clinical Oncology (2010)

4545 Background: The utility of bone scintigraphy in metastatic prostate cancer is limited by the risk of false positive findings. False positives can occur for many reasons, including a “flare” phenomenon due to the osteoblastic response that occurs as a result of bone healing after successful anti-neoplastic therapy. The incidence of bone flare in metastatic prostate cancer is unknown clinically but is important because it can result in patients (pts) being taken off active agents too soon on the basis of a potentially erroneous bone scans. Methods: 33 pts with progressive metastatic castration resistant prostate cancer (mCRPC), normal organ function, and no prior chemotherapy were enrolled on a phase II trial of Abiraterone acetate (AA) plus prednisone. PSA was obtained monthly and bone scan (BS) results, as reported locally, were evaluated along with PSA changes at baseline, just prior to starting cycle (c) 4 and c7. BS flare was defined as BS findings interpreted by a local radiologist as “disease progression” in the face of a ≥50% decline in PSA, which on follow up scan revealed an improved scan (i.e. disease regression). Results: A ≥50% decline in PSA at the time of c4 day 1 imaging was seen in 25/33 (76%) pts. Of these 25 pts, 23 were evaluable for flare (i.e. bone scans were evaluable at baseline, c4, and c7). Of 23 evaluable pts (each had a PSA response), 12 had discordant (worse) bone scans at c4 (52%). Of these 12 pts, 10 (83%) had subsequent improvements in BS at c7. Thus, overall BS flare was observed in 10/23 (43.5%) evaluable pts or 10/33 (30%) enrolled pts. Conclusions: Discordant bone scans occurred in over half of the mCRPC pts responding to AA by PSA criteria (12/23 patients). Over 80% of these scans were subsequently found to be flare phenomena, as demonstrated by improved follow up bone scans. Thus, overall, the flare phenomenon was a common event (43% of responding patients and 30% of all pts enrolled). BS “flare” and potentially false declarations of disease progression are common in this setting and should not be misconstrued as a treatment failure. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Oncology (Cougar Biotechnology)
NCCTG 96–94–53: Clinical variables associated with overall survival (OS), progression-free survival (PFS), 6 month progression-free survival (PFS6), immediate progression (ImmProg), and response in patients enrolled in recurrent glioma clinical trials
Authors: J. C. Buckner, K. Ballman, P. Schaefer, A. F. Furth, C. Giannini, B. W. Scheithauer, E. Galanis, K. A. Jaeckle
Journal: Journal of Clinical Oncology (2006)

1520 Background: Multiple variables may impact endpoints utilized to assess efficacy of investigational therapies for pts with recurrent gliomas. Understanding the nature of these variables should aid interpretation of results. Methods: 583 pts were enrolled to 15 consecutive recurrent glioma clinical trials conducted between 1980 and 2004. Identical patient, tumor, treatment and time variables were identified for each trial. Central neuropathology review was completed and pts were grouped by WHO diagnoses. Pts alive and progression-free at 6 months after start of treatment were a PFS6 ‘success’. Pts whose outcome was progression at first evaluation were classified as “Immediate Progression (ImmProg)”. Response was defined as regression, partial regression, or complete regression in the absence of worsening neurologic symptoms or increased corticosteroid dose. Univariable and multivariable Classification and Regression Trees (CART) models were used to identify factors associated with OS, PFS, PFS6, ImmProg, and Response. Results: Variables associated with outcomes for each endpoint assessed by CART models are shown in Table below. Conclusions: In clinical trials of recurrent glioma, age, PS, duration of disease, primary and recurrent histologic diagnosis, and primary and recurrent extent of resection are associated with outcomes. These variables should be validated in additional datasets for potential inclusion in reports of future clinical trials. Endpoint Independent Variables OS Primary histologic diagnosis; diagnosis at recurrence; Age; ECOG Performance score; Disease duration PFS Primary histologic diagnosis; ECOG Performance score; Disease duration; Resection extent at recurrence PFS6 Primary histologic diagnosis; Disease duration; Resection extent at recurrence ImmProg ECOG Performance score; Primary histologic diagnosis; diagnosis at recurrence; Duration of disease; extent of primary resection Response Age, ECOG Performance score; Primary histologic diagnosis; diagnosis at recurrence; Duration of disease; Extent of resection at recurrence No significant financial relationships to disclose.
Pharmacokinetics (PK) and Pharmacodynamics (PD) of a New Direct Thrombin Inhibitor (DPOC-4088) After Single Oral Doses of Two Prolonged Release Formulations in Healthy Male Subjects,
Authors: Luc M Van Bortel, Griet Van Lancker, Henri Vanden Bavière, Willem Hettema, Edwin Spaans, Sankar Ramakrishnan, Venkatesan Elumalai, Suryakumar Jayanthi, Stephane E Allard
Journal: Blood (2011)
Epidermal growth factor receptor (EGFR) activating mutations (muts) in the tyrosine kinase (TK) domain correlate with gefitinib response in chemorefractory non-small-cell lung cancer (NSCLC)
Authors: M. Taron, Y. Ichinose, R. Rosell, T. Mok, B. Massuti, C. Manegold, C. Queralt, T. Jahan, V. Hsue, D. Jablons
Journal: Journal of Clinical Oncology (2005)

7087 Background: EGFR activating muts in the TK domain confer a strong sensitivity to gefitinib. Methods: We examined EGFR muts at exons 18, 19 and 21 in tumor tissue from 68 gefitinib-treated, chemorefractory, advanced NSCLC patients (p) from the US, Europe and Asia and in a highly gefitinib-sensitive NSCLC cell line and correlated their presence with response and survival. In addition, in a sub-group of 28 p for whom remaining tumor tissue was available, we examined the relationship between EGFR muts, CA repeats, EGFR and caveolin-1 mRNA levels, and EGFR amplification. Results: Seventeen p had EGFR muts. All muts were found in lung adenocarcinomas. Objective response was observed in 16/17 (94.1%) p harboring EGFR muts, in contrast with 6/51 (12.6%) with wild-type EGFR (P<0.0001). Probability of response was significantly increased in non-smokers, p receiving a greater number of prior chemotherapy regimens, Asians and younger p. Median survival was 18.7 months for p with EGFR muts and 13.5 months for those with wild-type EGFR (P=0.009). EGFR muts tended to be associated with long CA repeats and gene amplification but not with EGFR and caveolin-1 mRNA overexpression (P=ns). Conclusions: The presence of EGFR muts is a major determinant of gefitinib response, and targeting EGFR should be considered in preference to chemotherapy as first-line treatment in lung adenocarcinomas that have demonstrable EGFR muts. No significant financial relationships to disclose.
A phase II study of a weekly schedule of BMS-247550 for patients with hormone-refractory prostate cancer: A trial of the Eastern Cooperative Oncology Group (E3803)
Authors: G. Liu, W. Wang, R. Dipaola, M. Carducci, G. Wilding
Journal: Journal of Clinical Oncology (2006)

4618 Background: BMS-247550 (ixabepilone) is an epothilone B analogue with activity in taxane-resistent cancer cell lines. Ixabepilone has been administered using a q3wks schedule with significant neutropenia observed. Here we assess the activity and toxicity of ixabepilone, administered using a weekly schedule, in men with metastatic hormone-refractory prostate cancer. Methods: Patients with metastatic hormone-refractory prostate cancer (chemonaive and prior taxane) were treated with ixabepilone at 20 mg/m 2 IV weekly × 3, in 4 wk cycles. This non-comparative study had a planned accrual of 29 chemonaive and 27 prior-taxane treated patients in order to detect a 50% PSA reduction using Consensus Criteria in at least 50% (91% power, α = 0.10) chemonaive and 30% (power 90%, α = 0.10) prior-taxane treated patients. Results: 32 pts with chemonaive and 37 pts with prior-taxane have been enrolled on this study. Median follow-up is 1.8 and 4.1 months respectively. Safety data is reported for the first 56 subjects (24 chemonaive and 32 prior taxane). Hematologic toxicity: Grade 3/4 neutropenia was seen in 10 pts (5 chemonaive, 5 prior-taxane). No significant thrombocytopenia was observed. Grade 3/4 neuropathy was seen in 7 pts (2 chemonaive, 5 prior-taxane). Grade 3 fatigue noted in 8 (3 chemonaive, 5 prior-taxane), grade 3 diarrhea in 5 (4 chemonaive, 1 prior-taxane), and grade 3 nausea in 3 subjects. Lastly, 2 subjects were reported to have developed a grade 3 ileus during therapy. Conclusions: In 56 subjects, BMS-247550 was found to have an acceptable toxicity profile when administered using a weekly schedule. Myelosuppression appeared to be improved, as compared to historical data with the q3wk schedule, using this dose and schedule. PSA/objective responses have been seen but at this time, no conclusion regarding its activity in the first or second-line setting can be made, as the response assessment is ongoing. Complete toxicity and response data will be presented for the entire group. No significant financial relationships to disclose.
Prospective evaluation of epoetin-alfa (EA) vs epoetin-beta (EB) vs darbepoetin (DE) in anemic cancer patients (pts) receiving chemotherapy (CT): Early results of an independent observational survey by the Italian ReVERTO network
Authors: C. F. Pollera, F. Nelli, T. Gamucci, I. Sperduti, A. M. Giampaolo, L. Moscetti, G. Tonini, L. Mentuccia, M. Nardi, E. Cortesi
Journal: Journal of Clinical Oncology (2006)

18548 Background: Direct comparison of EA vs EB vs DE has never been performed. In order to define the efficacy, impact on quality of life (QL) and pt’s preference, a prospective observational comparison of erythropoietic agents has been carried out. Methods: Anemic pts (hgb &lt;11 gr/dL) scheduled to receive at least 3 cycles of CT were stratified according to 5 factors (platinum-based CT vs non-platinum; hgb ≤9,5 vs &gt;9,5; PS ≤0–1 vs &gt;1; previous CT vs upfront CT; and previous antianemic therapy vs not) and were autonomously assigned by 15 investigators to EA (3 times a week) or EB (3 times a week and only in pts receiving platinum-based CT) or DE (once a week) therapy. Efficacy by hgb level changes and transfusion needing was evaluated after each cycle of CT, QL by Fact-An questionnaire after 1 and 3 cycles of CT, and pt’s preference for standard vs weekly schedule at least once thereafter. Results: From 09/04 to 12/05 177 pts were recruited: 41%, 39% and 20% were assigned to DE, EA and EB, respectively. Severe anemia at baseline (≤9,5) was reported in 29% of pts, whereas 47% received platinum-based CT. Stratifying categories were well balanced among the treatment groups. Baseline mean hgb values were 9.7, 9.9, and 10 for DE, EA and EB, respectively. As of the general population, DE produced higher subsequent mean hgb increase in respect to EA and EB (Mean increase [gr/dL] for DE: 0.84, 1.58, 2.03; EA: 0.34, 0.84, 1.68; EB: 0.76, 1.54, 1.17). No difference was observed neither among pts receiving platinum-based CT, (mean increase: DE: 0.34, 1.76, 2.8; EA: 0.7, 1.27, 2.14; EB: 0.76, 1.54, 1.71) nor among pts with severe anemia at baseline (DE: 0.98, 2, 2.6; EA: 1.24, 1.94, 3.13; EB: 1.25, 2.25, 2.75). Transfusion needing ranged from 7% for DE to 3% for EB without any significant difference. To date 67% of pts completed at least one subsequent QL valuation, whereas 62% gave their preference for treatment schedule. Conclusions: Early results of our prospective analysis show that antianemic therapy with D is at least as effective as standard schedule of EA or EB. Efficacy of DE seems confirmed in pts with bad prognostic categories for anemia. Major data on QL and pt’s preference will be presented. No significant financial relationships to disclose.
Biomarkers of Cartilage and Bone Damage as a Measure of Joint Damage in Haemophilia.
Authors: Nathalie W.D. Jansen, Goris Roosendaal, Bjorn Lundin, Lily Heijnen, Matthias Theobald, Johannes W.J. Bijlsma, Floris P.J.G. Lafeber
Journal: Blood (2008)
Abstract 17022: RAGE Suppresses Adaptive Upregulation of MCP-1 in Hind Limb Ischemia in Diabetic Mice
Authors: Xiaoping Shen, Rosa Rosario, Yu Shan Zou, Ann Marie Schmidt, Shi Fang Yan
Journal: Circulation (2012)

Diabetic subjects with foot ulceration and critical limb ischemia are at high risk for lower-extremity amputations. Our previous findings revealed that receptor for advanced glycation endproducts (RAGE) impaired angiogenesis and blood flow recovery in hind limb ischemia in diabetic mice. Here, we tested the hypothesis that RAGE modulates gene expression changes in the inflammatory response to hind limb ischemia in diabetic mice. Wild type (WT) and RAGE -/-  mice were rendered diabetic (D) with streptozotocin (stz); non-diabetic (ND) cohorts were treated with buffer alone. After two months of diabetes, at age 16 weeks, mice were subjected to femoral artery (FA) ligation. RNA was prepared from muscle tissues distal to the ligation on day 7 after surgery and subjected to gene expression profiling using “Angiogenesis” focused PCR arrays to identify the genes impacted by diabetes and RAGE in hind limb ischemia. An ≈ 8-fold increase in monocyte chemotactic protein-1 (MCP-1/CCL2) was observed in D RAGE -/-  mice vs D WT mice post-ligation. These results were further validated by real-time PCR analysis. Our data demonstrated significant increase in MCP-1/CCL2 transcripts in RAGE /-  vs. WT mice in non-diabetes post-ligation as well (p +  cells were evident in RAGE -/-  vs. WT mice muscle tissues in both non-diabetes and diabetes (p
Early indicators of accrual success: Time-to-first-patient and accrual performance at an anticipated enrollment milestone-A study of NCI-CTEP-sponsored clinical trials.
Authors: S. K. Cheng, M. S. Dietrich, S. Finnigan, D. M. Dilts
Journal: Journal of Clinical Oncology (2010)

6001 Background: This research investigates whether indicators of time from trial opening to first enrollment and accrual performance may predict ultimate successful trial accrual. Methods: National Cancer Institute Cancer Therapy Evaluation Program (NCI-CTEP) Sponsored trials for all therapeutic, nonpediatric phase I, I/II, II, and III trials activated and closed to accrual from 2000 to 2007 were investigated (n = 764). Two indicators were evaluated. The first indicator was months from opening of the trial to first patient enrolled. The second indicator was the accrual performance, computed as the percentage of actual accrual compared to the minimum accrual goal, evaluated at the anticipated time to achieve the minimum goal. For example, if a trial had a minimum accrual goal of 150 and was anticipated to accrue 15 pts/month, the anticipated time is 10 months. Multivariable logistic regression analysis was used to calculate unadjusted and adjusted odds ratios, controlling for study size, cancer incidence, and cancer mortality. Results: Trials that enrolled the first patient beyond the first two months of study activation were statistically significantly less likely to achieve the minimum accrual goal regardless of the time they remain open (odds ratio:0.616; 95% CI:0.464-0.875). Almost half of all trials (n = 379, 49.6%) enroll the first patient outside this window. Overall, 18.5% (n = 141) of CTEP-approved oncology trials achieve their minimum accrual goal within their anticipated time. Of the trials that remained open after this time (n = 603, 78.9%), trials that did not enroll a least 60% of their minimum goal within the anticipated period were statistically significantly less likely to achieve this minimum accrual goal by study closure, regardless of the time to closure (odds ratio:0.190; 95% CI: 0.055- 0.652). Conclusions: Early indicators in accrual performance can be used to identify trials that are highly likely to close without achieving their intended accrual goal. Time to first patient and accrual performance at anticipated trial enrollment time appear to be two such predictors. No significant financial relationships to disclose.
Tolerability of pemetrexed versus placebo as a maintenance therapy in advanced non-small cell lung cancer: Evidence from a large randomized study
Authors: C. C. Zielinski, S. Yang, A. Santoro, R. Ramlau, A. M. Liepa, P. Peterson, T. Brodowicz, J. Madhavan, F. A. Franke, B. Cucevic
Journal: Journal of Clinical Oncology (2008)

8060 Background: Cytotoxic chemotherapy seeks to reduce or stabilize tumor burden in advanced non-small cell lung cancer (NSCLC). Administration, however, is limited by cumulative toxicity or diminished efficacy over time. We present results on the tolerability of single-agent pemetrexed (Pem) from a phase III, double-blind study, in which maintenance pemetrexed significantly improved progression-free survival (PFS), compared to placebo. Methods: Following 4 cycles of platinum-based doublet chemotherapy, advanced NSCLC patients (pts) with stable or responding disease were randomly assigned 2:1 to receive Pem 500 mg/m2 or placebo infusion every 21 days. Toxicity was assessed using CTCAE (v3) and compared with Fisher’s exact test. Pts completed the Lung Cancer Symptom Scale (LCSS) prior to start of each cycle. Time to worsening of symptoms (TWS) was estimated for each LCSS item based on a 15-point increase from baseline and analyzed using Kaplan-Meier and Cox methods. Results: 663 pts were randomized. Known prognostic factors, as well as baseline LCSS scores, were well balanced between arms. Comparing Pem to placebo: median number (range) of cycles was 4 (1–34) and 3 (1–30); 43% and 25% of pts received ≥ 6 cycles; 4% vs 1% required dose reductions. Deaths on study (any cause) were similar between arms (8.6% vs 9.0%) although pts with ≥ 1 SAE possibly related to study drug were greater for Pem (19 [4.3%] vs 0) Hazard ratios for TWS showed no significant difference or favored Pem. Conclusions: Single-agent Pem is well tolerated as maintenance therapy for pts with advanced NSCLC. Pem provides significantly increased PFS with low rates of toxicity, potential long duration of therapy, and generally comparable-to-placebo patient-reported outcomes. CTCAE Grade 3–4 Toxicities occurring in ≥ 2.5% of Randomized Patients Pem (N=441) Placebo (N=222) P-value Anemia 20 (4.5%) 3 (1.4%) 0.041 Anorexia 11 (2.5%) 2 (0.9%) 0.237 Cough 9 (2.0%) 9 (4.1%) 0.137 Dyspnea 27 (6.1%) 7 (3.2%) 0.135 Fatigue 37 (8.4%) 11 (5.0%) 0.115 Neutropenia 14 (3.2%) 4 (1.8%) 0.448 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company