tbuckley/cabot-search huggingface dataset:
Abstract 3547: Are U.S. Adults with Heart Disease Meeting Physical Activity Recommendations?
Authors: Guixiang Zhao, Earl S Ford, Chaoyang Li, Ali H Mokdad
Journal: Circulation (2007)

The benefits of physical activity on risk of cardiovascular disease have led to recommendations to increase its levels in patients with heart disease. We investigated the degree of compliance with national physical activity recommendations, issued by the Centers for Disease Control and Prevention and the American College of Sports Medicine as well as the U.S. Surgeon General, among U.S. adults with coronary heart disease (heart disease) in comparison with people without heart disease using data from 2005 Behavioral Risk Factor Surveillance Survey. Information on heart disease or physical activity was self-reported. Moderate physical activities were those that cause small increases in breathing or heart rate (e.g., brisk walking) while vigorous physical activities were those that cause large increases in breathing or heart rate (e.g., running). Total physical activity was defined as participation in either moderate or vigorous physical activity. A total of 297,145 participants aged 18 years or older were included in our analyses and 24,496 people had heart disease. The age-adjusted prevalence and the odds ratios (ORs) for meeting total, moderate or vigorous physical activity recommendations were calculated in people with or without heart disease. People with heart disease were less likely to engage in physical activity at recommended levels than those without heart disease (41%, 32% and 22% versus 49%, 37% and 29%, respectively, for meeting total, moderate or vigorous physical activity recommendations, P&lt;0.01 for all). The unadjusted ORs for adults with heart disease who met total, moderate or vigorous physical activity were 0.61 [95% confidence interval (CI): 0.58–0.65], 0.76 (95% CI: 0.72–0.80), and 0.45 (95% CI: 0.42–0.49), respectively. These ORs were attenuated but remained significant after adjustment for demographic variables, or after further adjustment for diabetes status and limitations for physical activity performance [The ORs were 0.92 (95% CI: 0.87–0.97), 0.95 (95% CI: 0.89–1.00) and 0.88 (95% CI: 0.81–0.95), respectively]. Our findings demonstrate the need for continuing efforts to promote physical activity in patients with heart disease who do not have limitations for performing physical activity.
Suramin: development of a population pharmacokinetic model and its use with intermittent short infusions to control plasma drug concentration in patients with prostate cancer.
Authors: D I Jodrell, L M Reyno, R Sridhara, M A Eisenberger, K H Tkaczuk, E G Zuhowski, V J Sinibaldi, M J Novak, M J Egorin
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study aimed to (1) develop a population pharmacokinetic model for suramin; (2) use Bayesian methods to assess suramin pharmacokinetics in individual patients; (3) use individual patients' pharmacokinetic parameter estimates to individualize suramin dose and schedule and maintain plasma suramin concentrations within predetermined target ranges; and (4) assess the feasibility of outpatient administration of suramin by intermittent, short infusions. METHODS Plasma suramin concentrations were measured by high-performance liquid chromatography (HPLC), and compartmental pharmacokinetic models were fit using a Bayesian algorithm. Population pharmacokinetic models were developed using an iterative two-stage approach. Estimates of each patient's central-compartment volume were used to calculate suramin dosage. Simulation of that patient's suramin clearance was used to predict the time of his next dose. Using this approach, plasma suramin concentration was maintained at between 200 and 300, 175 and 275, 150 and 250, or 100 and 200 microgram/mL in four sequential patient cohorts. The ability of two- and three-compartment, open, linear models to fit the pharmacokinetic data was compared. Population pharmacokinetic parameters were estimated, using both two- and three-compartment structural models in 69 hormone-refractory prostate cancer patients. RESULTS Target plasma suramin concentrations in individual patients were rapidly achieved. Concentrations were maintained within desired ranges for &gt; or = 85% of treatment duration in all cohorts. A three-compartment, open, linear model described suramin pharmacokinetics better than did a two-compartment, open, linear model. Population pharmacokinetic estimates generated for two- and three-compartment pharmacokinetic models demonstrated modest interpatient pharmacokinetic variability and the long terminal half-life of suramin. CONCLUSION Suramin can be administered by intermittent short infusion. Adaptive-control-with-feedback dosing facilitated precise control of plasma suramin concentrations and allowed a number of different concentration ranges to be studied. This approach is expensive and labor-intensive. Although we have demonstrated the ability to control drug exposure, simpler dosing schedules require critical evaluation. Population pharmacokinetic parameters generated in men with hormone-refractory prostate cancer will facilitate rational design of such schedules.
Preliminary results of a phase II study of low dose continuous chemotherapy for relapsed/refractory lymphoid malignancies
Authors: H. Sayar, F. C. Lee, I. Rabinowitz, K. K. Rasila, R. Hromas
Journal: Journal of Clinical Oncology (2005)

6732 Background: Low dose continuous (metronomic) chemotherapy has been shown to be effective in overcoming drug resistance and also exerting antiangiogenic activity. The aim of this study is to evaluate this approach in cases of relapsed/refractory lymphoid malignancies. Methods: Patients with ECOG-PS 0–2, and adequate bone marrow, hepatic and renal function who had relapsed/refractory disease after at least two chemotherapy regimens were eligible. Treatment consisted of: Etoposide 50 mg/day oral X 14 days; Chlorambucil 0.1 mg/kg/day oral X 14 days; Vincristine 2mg IV on days 1 and 14; Dexamethasone 200 mg IV on days 1 and 14; Rituxan (only in patients who had previously received less than 8 doses) 375 mg/m2 IV on days 1 and 14. Each cycle was repeated every 28 days. Results: From October 2003 to December 2004 total of 6 patients were enrolled (study is still ongoing at the time of submission). Age 23 - 70. Four male and two female. 5 patients were evaluable. 2/5 had major response: one with follicular lymphoma, significant response after 2 cycles; one with diffuse gastrointestinal mantle cell lymphoma, significant response after 3 cycles. 1/5 had minor response: nodular sclerosing Hodgkin’s lymphoma, responded after 2 cycles. 2/5 did not respond. Toxicity: Neutropenia: 1/5 grade 3, 1/5 grade 4; Thrombocytopenia: 1/5 grade 1; Neuropathy: 1/5 grade 2, 1/5 grade 3. Nausea: 2/5 grade 1, 1/5 grade 2. Conclusions: The preliminary results of this study indicate that metronomic administration of chemotherapy yields major and early response in some cases of relapsed/refractory lymphoid malignancies. No significant financial relationships to disclose.
Effect of relative cumulative dose-intensity on survival of patients with urothelial cancer treated with M-VAC.
Authors: H I Scher, N L Geller, T Curley, Y Tao
Journal: Journal of Clinical Oncology (1993)

PURPOSE To evaluate the received dose-intensity in a mature data set of patients with advanced urothelial cancer who received at least one cycle of the methotrexate (M), vinblastine (V), Adriamycin ([A], doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (C) regimen (M-VAC). PATIENTS AND METHODS Received dose-intensity was evaluated over time by summing doses over cycles for each patient, cumulating treatment times, and assuming four cycles of chemotherapy were planned. Relative cumulative dose-intensity was then calculated for individual patients at the end of each cycle. To assess a relationship with survival, relative cumulative dose-intensity was then used as a time-dependent covariate in Cox regression. RESULTS The median follow-up was 6 years and median survival 13.3 months, with 20 patients alive at the time of analysis. Out of a maximum of 1.0, the median relative dose-intensity for the M-VAC combination decreased from .69 to .59 from cycle 1 to cycle 4. Similarly, a decrease from .68 to .62 and from .80 to .72 was observed for A and C, respectively. The median received dose-intensity for A was 6.0 mg/m2/wk, and for C 14 mg/m2/wk. Neither the four-cycle relative cumulative dose-intensity for the M-VAC combination, nor the relative cumulative dose-intensities for A or C were found to be significant prognostic factors. CONCLUSION The absence of an effect for received dose-intensity on survival may reflect the low dose-intensities of the components of the regimen actually delivered in this study. The results question whether the individual agents can be escalated sufficiently, with growth factor support, to improve significantly complete response proportions, a prerequisite for increasing the proportion of long-term survivors.
Efficacy of natural antiinflammatories in primary rat tracheal epithelial cell transformation.
Authors: Sheela Sharma, Pu Gao, Barbara Wetmore, Vernon Steele
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4987 

We have developed and used a primary rat tracheal epithelial (RTE) cell transformation model for identifying potential chemopreventive agents belonging to different chemical classes/biological activity. The current study examined whether natural products with significant anti-inflammatory characteristics have chemopreventive activity in the same model system. RTE cells were treated with B[ a ]P alone or with five nontoxic concentrations of a natural anti-inflammatory product and the resulting foci at the end of 30 days were scored for inhibition of transformation. EP-1A, a sea cucumber fraction containing saponins , was tested at 0.01-1.0 µg/mL and it inhibited transformation in a dose-dependent manner with an IC50 of 0.1µg/ml. Similarly, CbrA5, a lipid fraction from sea cucumber, inhibited transformation at all concentrations (0.3-10µg/mL) with 100% inhibition at the highest dose and an IC50 of 0.3µg/mL. Green oil, another lipid compound from sea cucumber significantly inhibited B[ a ]P-induced transformation (0.1-10µg/mL) in a reverse dose-dependent manner with an IC50 of 0.1µg/mL. Frondanol, an oil extract from sea cucumber, was the only fraction that was not effective in this model. Iloprost, a stable prostacyclin analogue was highly effective (44-100 %) at higher concentrations (30-100 µM). Turmerin, a water soluble small peptide from turmeric, exhibited dose-dependent response with maximum inhibition (37%) at 10 µg/mL. In addition, turmerin showed excellent correlation between inhibition of transformation and effect on CK-14, survivin and apoptosis, biomarkers that appear at different stages of RTE transformation. The agents were rated based on the IC50 concentration from low high as follows: EP-1A ≤ Green oil< CBr5 <Turmerin<Iloprost. It appears that the RTE model system can be successfully employed to identify natural antiinflammotories, another class of cancer preventive agents. It is highly likely that these agents being natural products, have multiple biological activities which has contributed to their effectiveness in this primary cell respiratory model of transformation (Supported by NCI #N01-CN-43301).
Patient compliance with oral chemotherapy as assessed by a novel electronic technique.
Authors: C R Lee, P W Nicholson, R L Souhami, A A Deshmukh
Journal: Journal of Clinical Oncology (1992)

PURPOSE Previous reports have suggested low rates of compliance with the oral component of cancer chemotherapy, which, if confirmed, would have serious implications on treatment. Because of the uncertainties in the methodology used in previous studies, we have assessed compliance with a novel technique. PATIENTS AND METHODS An "intelligent" tablet bottle was used, which, unknown to the patient, electronically records the times of opening over a period of weeks. The records were scored for overall compliance (total number of bottle openings as a percentage of the prescribed number) and for daily and hourly irregularity indices. Twenty-one patients undergoing treatment for Hodgkin's or non-Hodgkin's lymphoma were monitored for a total of 65 treatment periods, each of up to 2 weeks (852 days in total). Eight measures of side effects and quality of life were self-assessed daily by the patients using a diary card. RESULTS The overall compliance was 100.6% +/- 20.6% (mean +/- SD). Overall compliance was lower (mean reduction, 10%) in treatment periods with drugs prescribed to be taken three times a day. It was not possible to demonstrate convincingly any relationship between compliance and any of the following: drug type, monitoring period sequence, the diary card scores of side effects and quality of life, number of relapses, and time since initial diagnosis. CONCLUSION These results are reassuring, but further work is in progress to measure compliance in other treatment regimens in which the side effects are more severe and the prognosis is worse.
A novel approach to rituximab biosimilar drug development.
Authors: S. M. Berry, D. J. Reitsma, A. J. Combest, J. K. Bryan, J. W. Adair, B. T. Healey, J. K. Viele
Journal: Journal of Clinical Oncology (2011)

e13064 Background: Regulatory uncertainty exists about the amount of data needed to prove biosimilarity and to extrapolate across indications. Extrapolation is especially challenging for a reference compound licensed as both an anticancer and an immunomodulating agent and where the mechanism of action may play a different role in each. However, if a biosimilar is shown to be similar to the reference compound in one indication, it is potentially more likely to be similar in another indication. Using a Bayesian approach, this may be captured through hierarchical modeling (borrowing-of-strength) across indications. We model a Bayesian hierarchical modeling (BHM) approach and a frequentist approach to support extrapolation of rituximab efficacy between follicular lymphoma (FL) and rheumatoid arthritis (RA) indications. Methods: We compared sample sizes for separate frequentist equivalence tests to a BHM approach with identical type I error and power. Frequentist sample sizes were computed in PASS. For the BHM, we assumed the log-odds ratios between the reference and biosimilar, θi (thus θi = 0 is complete equivalence), are modeled as N(μ,τ) with hyperpriors on μ and τ. The BHM borrows information across indications according to empirical similarity of the results. Results: See table. The BHM approach results in a 35% reduction in total sample size. Discussion will be required with regulatory authorities regarding the acceptability of proposed equivalence margins and the degree of confidence required to support extrapolation of efficacy across all indications. Conclusions: With a 35% reduction in sample size, the BHM approach enables borrowing across oncology and autoimmune indications with equal power and confidence. Frequentist and BHM phase III assumptions and sample sizes. Assumptions Frequentist Bayesian Indication FL RA FL RA Drug regimen R+CVP R+MTX R+CVP R+MTX Power 0.9 0.9 0.9 0.9 Alpha 0.05 0.05 0.05 0.05 Equivalence margin (%) 10 15 10 15 Rituximab response rate (%) 81 51 81 51 Subjects per arm 353 254 225 170 Randomization (reference rituximab: rituximab biosimilar) 1:1 1:1 Total evaluable subjects 706 508 450 340 Total evaluable subjects overall 1,214 790 Abbreviations: FL, follicular lymphoma; R, rituximab; CVP, cyclophosphamide, vincristine, prednisone; MTX, methotrexate.
Long-term benefits of imatinib (IM) for patients newly diagnosed with chronic myelogenous leukemia in chronic phase (CML-CP): The 5-year update from the IRIS study
Authors: B. J. Druker, F. Guilhot, S. O’Brien, R. A. Larson
Journal: Journal of Clinical Oncology (2006)

6506 Background: IM was proven to be superior to IFN+Ara-C for newly diagnosed patients (pts) with CML-CP (O’ Brien et al, NEJM 2003). 1,106 pts were randomized between June 2000 and Jan 2001 to either IM 400 mg or IFN+Ara-C with 553 pts to each treatment. This abstract is based on data collected up to 54 months after last patient had been recruited on IM. 60-months (5-year) data will be available for presentation. Methods: Evaluations included complete hematologic response (CHR), complete/partial cytogenetic response (CCyR/PCyR - defined as 0% / 1–35% Ph+ metaphases respectively), major cytogenetic response (MCyR=CCyR+ PCyR), major molecular response (MMR) - defined as ≥ 3 log reduction of BCR-ABL transcript levels from the standardized baseline, time to progression - defined as loss of CHR/MCyR, evolution to accelerated phase/blast crisis (AP/BC), or death due to any cause during treatment, and overall survival. Results: With a median follow-up of 54-months, 72% of the 553 randomized pts remain on initial IM treatment (5% of pts discontinued due to adverse events, 9.5% due to unsatisfactory therapeutic effect and 11% due to other reasons another 2.5% crossed over to IFN+Ara-C). Overall, the cumulative best response rates of CHR, MCyR and CCyR are 97%, 88% and 82%, respectively. The overall estimated survival was 90% (93% when censored at bone marrow transplant). An estimated 84% of pts have not progressed on treatment and 93% of pts were free from progression to AP/BC. The annual rate of progression to AP/BC of &lt; 1% in the fourth year was lower than each of the first three years (1.5, 2.8, and 1.6%, respectively). Of the pts with MCyR at 12 months (n=436), an estimated 96% were free of progression to AP/BC at 54 months whereas it was only 81% for the 73 pts who did not achieve a MCyR at 12 months (p&lt; 0.001). No patient with a MMR within 12 months progressed to AP/BC within 54 months. Conclusions: This analysis confirms the high rates and durability of responses to IM. Encouragingly, the rate of progression in the fourth year was lower than in each of the preceding three years. Results further demonstrate the beneficial effect of cytogenetic and molecular responses on long-term outcomes. [Table: see text]
Patient and surgeon correlates of shared decision making for surgical breast cancer treatment
Authors: S. Hawley, P. Lantz, B. Salem, A. Fagerlin, N. Janz, M. Morrow, T. Hofer, D. Deapen, L. Liu, K. Schwartz, S. J. Katz
Journal: Journal of Clinical Oncology (2006)

6031 Background: The choice of surgical breast cancer treatment represents an opportunity for shared decision making (SDM), since both mastectomy and breast conserving surgery are viable options. Yet women vary in their desire for involvement in this decision. Correlates of SDM and/or the level of involvement in breast cancer surgical treatment decision-making are not known. Methods: Breast cancer patients of Detroit and Los Angeles SEER registries were mailed a questionnaire shortly after diagnosis in 2002 (N = 1,800, RR: 77%). Their responses were merged with a surgeon survey (N = 456, RR: 80%) for a dataset of 1,547 patients of 318 surgeons. Surgical treatment decision making was categorized into: 1) surgeon-based; 2) shared; or 3) patient-based. The concordance between a woman’s self-reported actual and desired decisional involvement was categorized as having more, less, or the right amount of involvement. Decision making and concordance were each analyzed as three-level dependent variables using multinomial logistic regression controlling for clustering within surgeons. Independent variables included patient clinical, treatment and demographic factors, surgeon demographic and practice-related factors, and a measure of surgeon-patient communication. Results: 37% of women reported the surgery decision was shared, 25% that it was surgeon-based, and 38% that it was patient-based. Two-thirds experienced the right amount of involvement, while 13% had less and 19% had more. Compared to women who reported a shared decision, those with surgeon-based decision were significantly (p &lt; 0.05) more likely to have male surgeons, and those reporting a patient-based decision were more likely to have received mastectomy vs. breast conserving surgery. Women who were less involved in the surgery decision than they wanted were younger and had less education, while those with more involvement (vs. the right amount) more often had male surgeons. Patient-surgeon communication was associated with decisional involvement. Conclusions: Correlates of SDM and decisional involvement relating to surgical breast cancer treatment differ. Determining patients’ desired role in decision making may as important as achieving a shared decision for evaluating perceived quality of care. No significant financial relationships to disclose.
Phase II study of ginkgo biloba in irradiated brain tumor survivors: Effects on quality of life (QOL), mood, and cognitive function.
Authors: A. Attia, L. D. Case, R. D'Agostino, G. J. Lesser, K. McMullen, M. J. Naughton, S. R. Rapp, R. Rosdhal, E. G. Shaw
Journal: Journal of Clinical Oncology (2010)

e12523 Background: Ginkgo biloba can improve cognitive function in patients with Alzheimer's disease and multi- infarct dementia. We conducted an open-label phase II study of this botanical product in symptomatic irradiated brain tumor survivors. Methods: Eligibility criteria included: age ≥ 18 years, life expectancy ≥ 30 weeks, partial or whole brain radiation ≥ 6 months before enrollment, no imaging evidence of tumor progression in previous 3 months, on stable or decreasing steroid dose, Karnofsky Performance Status (KPS) ≥ 70, and no brain tumor treatment planned while on study. The ginkgo biloba dose was 120 mg/day (40 mg tid) for 24 weeks followed by a 6-week washout period. Assessments performed at baseline, 12, 24 (end of treatment), and 30 weeks (end of washout) included KPS, functional assessment of cancer therapy-brain (FACT-Br), profile of mood states (POMS), mini-mental status exam (MMSE), trail-making test parts A (TMT-A) and B (TMT-B), digit span test (DST), Modified Rey-Osterrieth Complex Figure (ROCF), California Verbal Learning Test Part II (CVLT-II), and the F-A-S Test. Results: Of the 34 patients enrolled on study, only 19 (56%) completed 24 weeks of ginkgo. Five dropped out due to perceived lack of efficacy, five had dose-limiting toxicity, and five developed either intercurrent medical illness or brain tumor progression. Of the 19 remaining patients, there were significant improvements at 24 weeks: FACT brain subscale (p = 0.023), executive function (TMT-B) (p = 0.011), attention/concentration (TMT-A) (p = 0.006), and nonverbal memory (ROCF - immediate/delayed recall) (p = 0.018/0.025). No other differences were observed. Conclusions: Although some improvement in QOL and cognitive function were noted with ginkgo biloba, the drop out rate was significantly higher than our published results with donepezil (Aricept) (Shaw EG et al, J Clin Oncol 24:1415, 2006). Thus, we did not pursue further studies with ginkgo biloba. This study was supported by NIH/NCI/DCP grant 2 U10 CA 81851-09-13. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai