tbuckley/cabot-search huggingface dataset:
Long-term prostate-specific antigen (PSA) control in prostate cancer (PCa) patients switched from leuprolide to degarelix or receiving continuous degarelix treatment.
Authors: N. D. Shore, J. W. Moul, E. Crawford, T. Olesen, B. Persson
Journal: Journal of Clinical Oncology (2010)

4673 Background: Gonadotropin releasing-hormone (GnRH) blockers are a new type of fast-acting hormonal therapy for prostate cancer, which are devoid of agonist-associated surge/microsurges. Degarelix (approved dose 240/80 mg), a new GnRH blocker, was recently compared with leuprolide over 1-year of prostate cancer treatment in the CS21 trial. Here we report long-term PSA and musculoskeletal adverse event (AE) data from the extension study (CS21A). Methods: Patients with histologically confirmed prostate cancer were randomized to degarelix [starting dose 240 mg, and monthly maintenance doses of 80 mg (n=207) or 160 mg (n=202)], or leuprolide 7.5 mg/month (n=201). After 1 year, patients receiving leuprolide were re-randomised to degarelix 240/80 mg or 240/160 mg treatment. PSA progression-free survival (PFS) was defined as time to first of PSA failure (i.e. two consecutive increases in PSA of 50% and ≥5 ng/mL compared with nadir) or death. Data were also assessed by baseline PSA level. Results: After 1 year of treatment, the PSA failure rate decreased in patients switched from leuprolide to degarelix and the Kaplan-Meier curves for PSA PFS became superimposed. An additional analysis (October 2009) indicated a significant PSA PFS hazard change from 0.20 events/year in the first year to 0.09 events/year following the switch for leuprolide patients (p=0.0059); the corresponding hazards for degarelix at these time points were 0.11 and 0.14 (p=0.45). The same pattern occurred in patients with baseline PSA levels >20 ng/mL (leuprolide year 1: 0.38 vs 0.20 post switch [p=0.0367]; degarelix: 0.23 vs 0.23 [p=0.94]). Up to 1 year, musculoskeletal and connective tissue AEs occurred in 17% (degarelix) vs 26% (leuprolide; p<0.05) of patients. Beyond 1 year, these AEs were similar in the two groups (16% vs 18% [p=0.75]). Conclusions: These data suggest that patients with hormone-sensitive PCa receiving leuprolide experience improved PSA control after switching to degarelix. Patients receiving continuous degarelix have fewer musculoskeletal AEs. Further studies are required to confirm these findings. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ferring Pharmaceuticals Ferring Pharmaceuticals Ferring Pharmaceuticals Ferring Pharmaceuticals
Regional hyperthermia (RHT) improves response and survival when combined with systemic chemotherapy in the management of locally advanced, high grade soft tissue sarcomas (STS) of the extremities, the body wall and the abdomen: A phase III randomised pros
Authors: R. D. Issels, L. H. Lindner, P. Wust, P. Hohenberger, K. Jauch, S. Daugaard, U. Mansmann, W. Hiddemann, J. Blay, J. Verweij
Journal: Journal of Clinical Oncology (2007)

10009 Background: Patients (Pts) with locally advanced, high-grade STS are at significant risk for local failure and for metastasis. We evaluated the ability of RHT to improve the outcome in pts who are treated with neoadjuvant chemotherapy. Methods: Eligibility included pts with STS = 5 cm, grade II/III, deep and extracompartmental, stratified according to site (E = extremity vs. Non-E = body wall and abdomen). Pts were randomly assigned to systemic chemotherapy (etoposide 250 mg/m 2 ; ifosfamide 6 g/m 2 ; adriamycin 50 mg/m 2 ) alone (EIA) or to systemic chemotherapy combined with RHT (EIA + RHT) administered for 4 cycles every 3 weeks both prior and after local aggressive therapy (surgery + radiotherapy), respectively. Primary endpoints were local progression free survival (LPFS) and disease free survival (DFS). Objective (CR + PR) response rate (ORR) evaluated after 4 cycles (EIA vs EIA + RHT) was a secondary endpoint. A total of 340 pts was required to show an improvement in median LPFS of 19.2 mos for EIA + RHT (a=5% type I, 20% type II error). Results: Pts characteristics were well balanced between treatment arms. After median follow-up of 24.9 months (mos) an intention-to-treat analysis showed a significantly superior DFS for pts who received EIA + RHT (n=169) compared to those treated with EIA alone (n=172) (median DFS: 31,7 mos and 16,2 mos; log-rank p=0.003; Hazard ratio=0.65; CI95=0.48- 0.87, p=0.004). The median LPFS was estimated 45,3 mos for EIA + RHT and 23,7 mos for EIA (log-rank p=0.015; Hazard ratio=0.66; CI95=0.48 - 0.90, p=0.01). At 2 years, LPFS rates for E (149 pts) and for Non-E (192 pts) were significantly better for EIA + RHT vs EIA alone (E: 84% vs 64%; Non-E: 57% vs 39%) (p&lt;0.02). The ORR was significantly better for EIA + RHT (28,7%) vs EIA alone (12,6%) (p=0.002). Conclusions: Compared to chemotherapy alone, RHT combined with chemotherapy yields a statistically significant improvement in tumor response , DFS and LPS, in patients with locally advanced, high-grade STS. (Supported by Deutsche Krebshilfe and HGF VH-VI- 140) [Table: see text]
Venothromboembolism (VTE) in patients (pts) with acute myelogenous leukemia (AML).
Authors: N. V. Luong, M. Kroll, S. Faderl, D. Yang, A. Zalpour, K. T. Nguyen, D. Verma, G. Borthakur, H. Kantarjian, K. D. Vu
Journal: Journal of Clinical Oncology (2010)

9154 Background: Although cancer is a known risk factor for the development of VTE, little is known about the incidence and predisposing factors of VTE among pts with AML. Methods: A retrospective study was conducted to determine incidence and risk factors associated with development of VTE among pts with AML at MD Anderson Cancer Center between1999-2005. 996 pt medical records were reviewed. Analysis was performed using Stata 10. Results: Of 996 AML pts, 84 (8%) had VTE. 72 of the 996 pts had M3-AML; 8 (11%) of whom had VTE. Recurrent VTE occurred in 16 (19%) of 84 pts. Median age of pts with VTE was 60 yrs (range 14-89 yrs). VTE occurred in upper extremities (61%), lower extremities (28%), and pulmonary vasculature (11%). At time of AML diagnosis, 12 (14%) pts were found to have VTE. 37 (44%) VTE occurred within the first 3 months of AML diagnosis, with 31% occurring during induction. At time of VTE, platelet count (x109/L) was ≤50 in 56%, 51-99 in 24%, 100-299 in 14%, ≥300 in 2%, and unknown in 4%, p <0.001. In a univariate model, in comparison with pts aged 15-39, pts aged 40-59 yrs had a 49%-reduced risk (95%CI: 0.28-0.94) and pts aged ≥ 60 yrs had a 58%-reduced risk (95% CI: 0.23-0.75) of developing VTE. Pts with a history of VTE were 2.44 times (95%CI: 0.9-6.6) more likely to develop VTE. Pts with history of pulmonary disease were 2.06 times (95% CI: 1.15-3.71) more likely to develop VTE. Pts who used hormonal therapy were 2.02 times (95%CI: 1.05-3.9) more likely to develop VTE than non-users. In a multivariate model, the only significant predictor of VTE was prior history of VTE whereas age ≥ 60 yrs had reduced risk.Of 84 pts, 39(46%) received anticoagulation (AC) therapy; of these, 10 pts had bleeding events requiring consultation, only one of which was documented to be associated with AC; 3 other bleeding events were possibly related to AC. There were no major bleeding events documented. 4 of the 10 pts who had bleeding events also had recurrent VTE. Of 45 pts who did not receive AC, 5 (11%) developed recurrent VTE. Yet, 11 (28%) of the 39 pts who did receive AC did have recurrent VTE. Conclusions: AML pts have high VTE and recurrent rates. Prospective studies in pts diagnosed with AML need to focus on risk factors and guidelines for prevention and management of VTE. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
Determining the dose of degarelix for effective therapy of prostate cancer patients as investigated by the degarelix study groups
Authors: Bertrand Tombal, Peter Iversen, Hendrik Van Poppel, Teuvo L. Tammela, Jean J. de la Rosette, Jan-Erik Johansson, Bo-Eric Persson, Jens-Kristian Jensen, Tine Kold Olesen
Journal: Annals of Oncology (2006)
Clinically significant fatigue in recurrence-free prostate cancer survivors
Authors: D. J. Storey, D. McLaren, M. Shipway, I. Butcher, S. Liggatt, R. O'Dea, J. F. Smyth, M. Sharpe
Journal: Journal of Clinical Oncology (2007)

9044 Background: In the absence of definitive evidence of best disease control, treatment decisions for early prostate cancer should consider likely long term side effects and quality of life. Fatigue is an acute side effect of treatment but there are no data about long term clinically significant fatigue (CSF) in recurrence free prostate cancer survivors. This study presents the prevalence, associations and predictors of CSF after radical prostatectomy (RP) or radiotherapy (XRT). Methods: A postal questionnaire survey of 416 recurrence free men treated at a regional cancer centre &gt;1 year previously. CSF was defined as global Brief Fatigue Inventory score &gt;3. Other measures: Hospital Anxiety and Depression Scale (HADS), International Prostate Symptom Score (IPSS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, clinical and demographic information. Relationships between these factors and CSF were explored in univariate and then multivariate logistic regression analyses. Results: 91% (377/416) of questionnaires were analyzable. Mean age was 72 years (SD 6.1) and median time since treatment was 56 months (range 13–233). The prevalence of CSF was 29% (108/377) overall; 22% (29/133) post RP and 33% (79/244) post XRT. Univariate and multivariate associations of CSF predictors are shown below. Patients with CSF also had poorer quality of life, physical, role, and social function (all p&lt;0.001). CSF was not associated with age, social deprivation category or time since treatment. Conclusions: Almost a third of recurrence free prostate cancer survivors have CSF. RP is associated with less CSF post treatment than XRT, but treatment type did not remain statistically significant in a multivariate analysis controlling for other factors. Depression at outcome had the strongest association with CSF. Other associated variables were IPSS&gt;7, comorbid medical conditions and anxiety. Care should focus on optimising the identification and management of these conditions to improve fatigue. [Table: see text] No significant financial relationships to disclose.
Antiemetic efficacy of selective serotonin receptor (5HT3) antagonist, granisetron, on delayed chemotherapy-induced nausea and vomiting (CINV) in CPT-11 and 5-FU based chemotherapy (CT)
Authors: M. Ikeda, I. Seshimo, O. Takayama, M. Yasui, H. Fukunaga, M. Ikenaga, H. Yamamoto, M. Ohue, M. Sekimoto, M. Monden
Journal: Journal of Clinical Oncology (2004)

8187 Background: Though significant advances have been made in cancer treatment, CINV still remains significant patients (pts) concerns. Antiemetic guidelines based on emesis rate category have been proposed for the prevention of CINV (Support Care Cancer 2002; 10: 519–22). Dexamethasone (Dex) and 5HT3 antagonist are recommended for the prevention of acute and delayed CINV of CT using high emesis category drugs. However, there is no standard recommendation for delayed CINV of moderate emesis category drugs, such as CPT-11. The efficacy of granisetron, 5HT3 antagonist, on delayed CINV after CPT-11 and 5-FU based CT was investigated. Methods: Pts who had a delayed CINV were eligible for the study. Treatment regimen was consisted of a 90-min infusion of CPT-11 150mg/m2 on day 1 and 15, and UFT 375mg/m2/day on days 3–7, 10–14, 17–21 and 24–28, q5w. All pts received intravenous betamethasone and granisetron for prophylaxis against acute emesis on the day of CPT-11 administration. When pts had delayed CINV, 2 mg of granisetron was orally administered on days 2–6, and 16–20 of next treatment cycle. The severity of their gastrointestinal symptoms (anorexia, nausea, vomiting) on days 2–7, and 16–21 was recorded every day according to NCI-CTC, and pts preference of this treatment was recorded using questionnaire on days 8 and 22. The efficacy of the treatment was assessed in each patient by the comparison of severity of CINV with or without oral granisetron. Results: 16 pts (53.3%) of 30 pts who had received the CT had delayed CINV. The incidence of grade 2 or more vomiting was significantly greater in female than in male pts (54.6% vs 32.1%, p=0.002). Although granisetron did not improve the overall incidence of anorexia, nausea, and vomiting, the incidence of grade 2 or more vomiting in female pts was significantly reduced by granisetron (54.6% vs 32.4%, p=0.001). The questionnaire on pts preference revealed 76% of pts had preference for the treatment. Conclusions: Oral administration of granisetron for prevention against delayed CINV might be effective in female pts. No significant financial relationships to disclose.
Determinants of accrual period of time in dose escalating phase I trials
Authors: E. Dansin, J. Bonneterre, A. Adenis, S. Clisant, C. Ferté, N. Penel
Journal: Journal of Clinical Oncology (2009)

2518 Background: New drug development is a time- and resource-consuming process. Phase 1 trials constitute a major key- step of this development. Shortening the accrual time may improve this process. Methods: 292 published phase-1-trials were retrospectively reviewed to establish the determinants of accrual period of time (APT) using Log-rank test and then Cox Model. Results: Out of 292 trials (1997–2008), only 107 reports (36%) described the accrual time (median: 20 months, 5–72). Phase-2- recommended dose was established in 87 studies (81%). Most of studies investigated regimens included cytotoxic drugs (77%) or molecular targeted therapies (29%). Most of parameters did not significantly affect the APT: nature and number of investigated drugs, duration of treatment cycle, phase 1 dedicated to specific tumoral subtypes, number of centers, method of drug escalation (classical 3+3 vs. accelerated titration design), type of dose increment (modified Fibonacci method vs. others) and presence of expanded cohort at the phase-II-recommended dose. Under univariate analysis, two parameters shortened the APT: studies conducted in USA vs. other place (19 vs. 21 months, p=0.03) and regimen with more than 2 dose-escalated drugs (13 vs. 21 months, p=0.003). One parameter was significantly associated with longer APT: starting dose justified by animal toxicology data (first-in-man studies) vs. previous clinical trials (22 vs. 19 months, p=0.03). Cox model analysis retained only one determinant: starting dose justified by animal toxicology data: HR=4.07 [1.45- 11.42], p=0.047. Conclusions: Few parameters influence the APT in the dose-escalation phase-1 setting. Real first-in-man phase 1 studies based on starting dose estimated from animal toxicological data require longer APT. [Table: see text]
Comprehensive cancer cachexia staging and its impact in the outpatient oncology setting: A phase II study
Authors: D. Blum, J. Hess, A. Omlin, G. Jurt, F. Strasser ABHPM
Journal: Journal of Clinical Oncology (2009)

e20530 Background: Symptom management in advanced cancer is based on appropriate and feasible syndrome staging. To test whether 1. various factors predict involuntary weight loss [WL], 2. patients [pts] attending a cachexia clinic [CC] improve nutritional intake [NI], and 3. eating-related distress [ERD] is a consequence of cachexia or psychological issues. Methods: The multidisciplinary CC (nurse, nutritionist, psycho-oncologist, palliative cancer care physician) applies standardized assessments (Symptom Visual Analogue Scales [VAS, 0=none, 10=severe], 2-day NI diary [% of calculated needs: calories, protein], secondary causes for impaired NI, weight history (2 months WL), Body Mass Index [BMI], C-reactive Protein [mg/dl, normal 8), ERD-VAS, Hospital Anxiety Depression Scale, spirituality [FICA]). Interventions include nutritional counseling, palliative cancer care and psychosocial supportive measures. Descriptive analysis, Spearman‘s Rank correlation and Factor analysis (Eigenvalue &gt;1) were performed. Results: 58 pts (age 65 years [mean; range: 38, 85]; 28F/30M; cancer types: 24 GI, 13 GU, 12 lung/ENT, 9 other; survival 151 days [7, 776]) had 6.9% WL (-6, 22; 21%&lt;2%), 21 kg/m2 BMI (15, 26), 52 CRP (1, 272; 32% normal), 5.6 anorexia, 1.6 anxiety, 6 HADS-A, 1.3 depression, 9 HADS-D, 68% of NI needs (1466kcal [400, 2700], 47g protein [15, 108]). WL correlated with NI kcal (r=-.29, p=.038) and protein (-.3,.035), not anorexia (.16), BMI (.032) or CRP (-.08); a 2 factor model (NI/anorexia/WL [.83/.79/.70], CRP/BMI [.86/.75] explains 67% variability. At second visit (21 days; 13, 64) 15/19 pts increased kcal (400kcal) and 15/16 protein (32g) NI, 6/17 weight. ERD correlated with anorexia (r=.56, p=.001) and depression (.48,.002), not anxiety (.23), WL (.038) or survival (-.15). A 3 factor model (ERD/anxiety/depression [.71/.85/.92], anorexia/survival [.82/.65], WL [.84]) explains 75% variability. Conclusions: A combination of clinical variables seems needed to characterize patients with involuntary WL. Most patients attending 2 consecutive cachexia clinic visits respond to multidimensional interventions. ERD seems to be associated both with loss of appetite and depression, not by WL or survival. Further testing of this intervention seems justified. [Table: see text]
EXCESS RISK OF DEATH FROM VENTILATOR ASSOCIATED PNEUMONIA: A REAPPRAISAL USING LONGITUDINAL CAUSAL ANALYSIS
Authors: Maarten Bekaert, JF Timsit, Johan Decruyenaere, M Garrouste-Orgeas, E Azoulay, D Goldgran-Toledano, Stijn Vansteelandt, Dominique Benoit
Journal: Intensive Care Medicine (2009)
Phase II trial of consolidation chest radiotherapy for extensive-stage small cell lung cancer.
Authors: D. Yee, C. A. Butts, Q. S. Chu, D. W. Fenton, A. Joy, T. J. Reiman, M. Smylie, W. Roa
Journal: Journal of Clinical Oncology (2010)

7044 Background: A recent randomized trial demonstrated the local control and overall survival benefits of radiotherapy (RT) given to a common recurrence region (brain) for extensive stage small cell lung cancer (ES-SCLC) patients who respond to chemotherapy. The chest is another common post-chemotherapy recurrence area in ES-SCLC, with historical post-chemotherapy chest failure rates exceeding 50%, many of which cause distressing symptoms which negatively impact patients' quality of life and/or hasten death. The purpose of this trial is to define the effect of post- chemotherapy chest RT for ES-SCLC on rate of development of symptomatic chest failures. Methods: Eligible patients had biopsy-proven ES- SCLC, attained an objective radiologic disease response after receiving at least one chemotherapy cycle and signed study consent. Target accrual was 33 patients. Study patients were also offered prophylactic cranial irradiation (PCI). PCI and chest RT were given simultaneously 4-6 weeks after chemotherapy completion. Three dimensional conformal techniques were used to plan thoracic RT and the target volume was the post-chemotherapy residual chest disease plus margin. PCI dose was 25 Gy/10 daily fractions. Chest RT dose was 40 Gy/ 15 daily fractions. Patients were followed during and after RT for toxicity, local control, disease-free and overall survival. Results: 32 of 33 accrued patients were evaluable. All but three patients completed RT with no delays. One patient received 1 chemotherapy cycle, three received 3 cycles and 28 received 4 cycles. There were 4 complete responses and 28 partial responses to chemotherapy. Maximal acute RT toxicity was grade 2 esophagitis (18 patients). There were no treatment-related deaths. With a median follow-up of 7.8 months, the median time to disease progression was 8.1 months. Median survival has not been reached. There have been 11 chest recurrences, 6 in the irradiated region and 4 being symptomatic. There have been 13 distant-only failures and 6 combined distant/chest failures. Conclusions: Our data suggests post-chemotherapy consolidation chest RT for ES-SCLC patients who respond to chemotherapy is well- tolerated and decreases chest failure rates compared to historical data. No significant financial relationships to disclose.
Phase II study of clofarabine and cytosine arabinoside in adult patients with relapsed AML and in elderly patients with untreated AML who are at high risk of anthracycline toxicity
Authors: E. D. Agura, R. Berryman, B. Cooper, J. Fay, H. Holmes, C. Maisel, A. Molina, L. Pineiro, E. Vance
Journal: Journal of Clinical Oncology (2007)

7064 Purpose: To evaluate the efficacy/safety of a novel AML regimen in elderly patients with heart disease or in patients with a contraindication to ‘standard‘ anthracycline-containing regimens. Patients and Methods: Phase II, open-label design. Eligible pts had elderly de-novo or relapsed AML or would not benefit from 7+3 or simlar therapy. Treatment was CLOF 40 mg/m 2 , Ara-C 1,000 mg/m 2 . (d1–5). Results: Patients were accrued and treated from April 2005 through Oct 2006. All pts signed IRB-approved consents. The median age was 67 years (range 38–82 years). Twenty (67%) subjects had received at least one prior cytoxic regimen (excluding 5-AZA). Significant cardiovascular (history of MI, bypass grafting, cardiomyopathy) was present in 43% (13/30) prior to therapy. Thirty pts were enrolled and all recieved at least one day of therapy. 1 pt died within 24 hours of starting treatment due to disease progression. Of the remaining, 29/30 received at least one complete cycle of therapy and 5 received 2 cycles. None received more than 2 cycles. Toxicities were greater in those receiving a second cycle. Grade 4 neutropenia developed in all patients. There were no cases of regimen-related cardiac toxicity. Most patients had some degree of edema and third-spacing syndrome. Several developed a significant but reversible acral rash. 25 patients survived &gt;28 days and are evaluable for hematologic response. The histologic response rate (RR) is 68% (17/25) consisting of 14 (56%) complete remissions (marrow blasts &lt;5%) and 3 (12%) partial responses (PR). There were 13 subjects with known cytogenetic abnormalities, 1 favorable and 12 unfavorable. Complete cytogenetic remissions (CytoCR) occurred in 4 of those patients, by chromosome analysis and/or FISH. Durable remissions and low toxicity allowed some patients to proceed to nonablative allogeneic stem cell transplantation. Conclusion: Clofarabine and Ara-C is an active and well tolerated regimen in myeloid malignancies including “elderly AML” a distinct entity usually associated with poor response rate and high treatment-related toxicities. Other drug combinations with clofarabine are ongoing in hematopoietic transplant and other high risk subgroups. No significant financial relationships to disclose.
Zinc deficiency in a premature infant
Authors: K Weismann, M Arrøe
Journal: BMJ (2013)

A premature infant with a birth-weight of 1,218 g developed severe zinc depletion about two months after birth. He had received his mother's breast-milk which was found to have a low zinc content of about 5 mumol/l. The clinical symptoms of zinc deficiency included stunted growth, catarrhal symptoms and a characteristic eczematous eruption on the face and diaper region known as acrodermatitis. Serum zinc was lowered (6.8 mumol/l) and so was serum alkaline phosphatase activity. Oral zinc sulphate supplementation, initially 22.5 mg daily and subsequently 11 mg zinc daily, had a prompt effect on the patient's well-being and the skin was restored to normal after about a week.