9 research outputs found
Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer
Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor-targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 ( P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates versus TAX327. Taxane-induced shifts in %ARNL may serve as an early biomarker of clinical benefit in patients treated with taxanes
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Relationship of auer rods and chromosome findings to outcome in eighty-nine adults with acute nonlymphoblastic leukemia
We performed cytogenetic analyses using banding techniques on 89 adults with acute nonlymphoblastic leukemia prior to receiving protocol chemotherapy. The relationships of cytogenetic findings both to outcome and to other pretreatment variables (particularly the presence or absence of Auer rods) were analyzed. Patients were followed up to 90+ months. When patients were grouped according to cytogenetic findings (NN: all normal metaphases; AA: all abnormal metaphases; AN: both normal and abnormal metaphases; F: no evaluable metaphases; I: insufficient (less than three) metaphases) no significant differences were noted with regard to age, sex, terminal transferase positivity, complete remission rate, remission duration or survival. The marrow aspirates of patients with only normal (69%) metaphases or no evaluable metaphases (64%) were more likely to display Auer rods than specimens from individuals with only abnormal (26%) or a mixture of normal and abnormal (42%) metaphases (
p=0.03). The presence of Auer rods in the pretreatment marrow aspirate was associated with an increased complete remission rate (71% vs 41%,
p=0.004), median remission duration (12 months vs 9 months,
p=0.02), and median survival (13 months vs 4 months,
p=0.01). Using multivariable analyses, the presence or absence of Auer rods was the pretreatment factor that most significantly predicted response and survival in this group of patients. The presence of a normal karyotype in the initial cytogenetic preparation is associated with the presence of Auer rods. The finding of Auer rods in the initial bone marrow predicts greater response and longer survival in acute nonlymphoblastic leukemia
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Severity of Aortic Atheromatous Disease Diagnosed by Transesophageal Echocardiography Predicts Stroke and Other Outcomes Associated with Coronary Artery Surgery: A Prospective Study
Advanced atheromatous disease of the thoracic aorta identified by transesophageal echocardiography (TEE) is a major risk factor for perioperative stroke.This study investigated whether varying degrees of atherosclerosis of the descending aorta, as assessed by TEE, are an independent predictor of cardiac and neurologic outcome in patients undergoing coronary artery bypass grafting (CABG). Intraoperative TEE of the descending aorta was performed on 189 of 248 patients participating in a randomized controlled trial of low (50-60 mm Hg) or high (80-100 mm Hg) mean arterial pressure during cardiopulmonary bypass for elective CABG. Aortic atheromatous disease was graded from I to V in order of increasing severity by observers blinded to outcome. Measured outcomes were death, stroke, and major cardiac events assessed at 1 wk and 6 mo. Nine of the 189 patients with TEE examinations had perioperative strokes by 1 wk. At 1 wk, no strokes had occurred in the 123 patients with atheroma Grades I or II, while the 1-wk stroke rate was 5.5% (2/36), 10.5% (2/19), and 45.5% (5/11) for Grades III, IV, and V, respectively (Fisherʼs exact test, P = 0.00001). For 6-mo outcome, advancing aortic atheroma grade was a univariate predictor of stroke (P = 0.00001) and death (P = 0.03). By 6 mo there were one additional stroke, three additional deaths, and one additional major cardiac event. Atheromatous disease of the descending aorta was a strong predictor of stroke and death after CABG. TEE determination of atheroma grade is a critical element in the management of patients undergoing CABG surgery.(Anesth Analg 1996;83:701-8