The Experts below are selected from a list of 114 Experts worldwide ranked by ideXlab platform
Mark J Mckeage - One of the best experts on this subject based on the ideXlab platform.
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randomized phase iii placebo controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent Vadimezan asa404 in advanced non small cell lung cancer
Journal of Clinical Oncology, 2011Co-Authors: Primo N Lara, Jeanyves Douillard, Kazuhiko Nakagawa, Joachim Von Pawel, Mark J Mckeage, I Albert, Gyorgy Losonczy, Martin Reck, Dae Seog Heo, Xiaolin FanAbstract:Purpose This phase III trial was conducted to test whether the novel vascular disrupting agent ASA404 (Vadimezan), when combined with first-line platinum-based chemotherapy, improves survival in patients with advanced non–small-cell lung cancer (NSCLC) versus chemotherapy alone. Patients and Methods Patients with advanced stage IIIB or IV NSCLC, stratified by sex and tumor histology, were randomly assigned 1:1 to paclitaxel (200 mg/m2) and carboplatin (area under the curve, 6.0) with or without ASA404 (1,800 mg m2), given intravenously once every 3 weeks for six cycles followed by maintenance ASA404 or placebo. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results One thousand two hundred ninety-nine patients were randomly assigned. The trial was stopped for futility at interim analysis. At final analysis, there was no difference in OS seen between ASA404 (n = 649) and placebo (n = 650) arms: median OS was 13.4 a...
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randomized phase iii placebo controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent Vadimezan asa404 in advanced non small cell lung cancer
Journal of Clinical Oncology, 2011Co-Authors: Primo N Lara, Jeanyves Douillard, Kazuhiko Nakagawa, Mark J Mckeage, I Albert, Gyorgy Losonczy, Martin Reck, Joachim Von Pawel, Abderrahim Fandi, Giorgio V ScagliottiAbstract:PURPOSE: This phase III trial was conducted to test whether the novel vascular disrupting agent ASA404 (Vadimezan), when combined with first-line platinum-based chemotherapy, improves survival in patients with advanced non-small-cell lung cancer (NSCLC) versus chemotherapy alone. PATIENTS AND METHODS: Patients with advanced stage IIIB or IV NSCLC, stratified by sex and tumor histology, were randomly assigned 1:1 to paclitaxel (200 mg/m(2)) and carboplatin (area under the curve, 6.0) with or without ASA404 (1,800 mg m(2)), given intravenously once every 3 weeks for six cycles followed by maintenance ASA404 or placebo. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: One thousand two hundred ninety-nine patients were randomly assigned. The trial was stopped for futility at interim analysis. At final analysis, there was no difference in OS seen between ASA404 (n = 649) and placebo (n = 650) arms: median OS was 13.4 and 12.7 months respectively (hazard ratio [HR], 1.01; 95% CI, 0.85 to 1.19; P = .535). Similarly, no OS difference was seen in the histologic (squamous or nonsquamous) and sex (male or female) strata. Median PFS was 5.5 months in both arms (HR, 1.04; P = .727), while ORR was 25% in both arms (P = 1.0). Overall rate of adverse events (AEs) was comparable between the ASA404 and placebo arms. Grade 4 neutropenia (27% v 19%) and infusion site pain (10% v 0.5%) were reported more frequently in the ASA404 arm. CONCLUSION: The addition of ASA404 to carboplatin and paclitaxel, although generally well tolerated, failed to improve frontline efficacy in advanced NSCLC.
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phase ii study of asa404 Vadimezan 5 6 dimethylxanthenone 4 acetic acid dmxaa 1800 mg m2 combined with carboplatin and paclitaxel in previously untreated advanced non small cell lung cancer
Lung Cancer, 2009Co-Authors: Mark J Mckeage, Michael B Jameson, Martin Reck, Mark Rosenthal, David Gibbs, P N Mainwaring, Lutz Freitag, Richard Sullivan, Joachim Von PawelAbstract:This single-arm phase II study evaluated the tumor-vascular disrupting agent ASA404 (Vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800mg/m(2) plus standard therapy of carboplatin and paclitaxel in patients with advanced non-small cell lung cancer (NSCLC). This ASA404 dose is 50% higher than that used in previous phase II studies. Thirty patients with histologically confirmed stage IIIb or IV NSCLC previously untreated with chemotherapy received carboplatin AUC 6mg/mlmin plus paclitaxel 175mg/m(2) plus ASA404 1800mg/m(2) every 21 days for up to six cycles. The addition of ASA404 1800mg/m(2) to standard therapy produced little change in the systemic exposure of either total or free carboplatin or paclitaxel, and was generally well-tolerated, with no cardiac serious adverse events or clinically relevant ophthalmic abnormalities. The best overall tumor response was partial response, which was seen in 37.9% of patients by independent assessment and in 46.7% by investigator assessment. Stable disease was seen in 48.3% of patients by independent assessment and in 43.3% by investigator assessment. Median time to tumor progression was 5.5 months by investigator assessment and median survival was 14.9 months. The data from this trial corroborate findings from a recent randomized phase II trial, which suggested improvements in efficacy variables, including survival, when ASA404 1200mg/m(2) was added to standard therapy for advanced NSCLC. The manageable safety profile, lack of adverse pharmacokinetic interactions and efficacy outcomes seen in this single-arm study suggest that ASA404 1800mg/m(2) is a viable dose for future combination studies.
Michael B Jameson - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetic evaluation of Vadimezan asa404 5 6 dimethylxanthenone 4 acetic acid dmxaa
Expert Opinion on Drug Metabolism & Toxicology, 2011Co-Authors: Michael B Jameson, Michelle HeadAbstract:Introduction: Understanding the pharmacokinetics (PK) and pharmacodynamics of a drug is important to optimizing its use. Vadimezan is a tumor vascular-disrupting agent that acutely disrupts blood flow within tumors and induces innate tumor immunity. It has enhanced the activity of anticancer treatments in preclinical models and early phase trials, although one Phase III trial result was negative and another is yet to be reported. Areas covered: Areas covered in this review are the preclinical and human PK and the inter-relationship among PK, toxicity and efficacy of Vadimezan as a single agent and in combination with other therapies. These data are derived from a literature search on Medline and also from conference proceedings, abstracts and trial reports available up to June 2011. Expert opinion: The disappointing results of one Phase III trial, despite the promising randomized Phase II trial data, highlight the challenges in translational research, especially in selecting the optimal development strate...
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the development of the tumor vascular disrupting agent asa404 Vadimezan dmxaa current status and future opportunities
Expert Opinion on Investigational Drugs, 2010Co-Authors: Michelle Head, Michael B JamesonAbstract:Importance of the field: Targeting tumor vasculature with antiangiogenic agents improves outcomes achieved with chemotherapy in some cancers, but toxicity limits their applicability. Tumor vascular-disrupting agents (tumor-VDAs) induce an acute collapse in tumor vascular supply; ASA404 (Vadimezan, 5,6-dimethylxanthenone-4-acetic acid [DMXAA]) is the tumor-VDA most advanced in clinical development. Recent randomized trials of ASA404 in combination with chemotherapy suggested a survival advantage in NSCLC comparable to that achieved with bevacizumab, but with little additional toxicity. Phase III trials in advanced NSCLC have completed accrual, and a review of this exciting agent is timely.Areas covered in this review: This review focuses on the development of ASA404 to date, its mechanisms of action, the current body of clinical research and potential avenues for therapeutic use. It includes all completed clinical trials since it entered clinical testing in 1995 through to 2009.What the reader will gain: T...
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phase ii study of asa404 Vadimezan 5 6 dimethylxanthenone 4 acetic acid dmxaa 1800 mg m2 combined with carboplatin and paclitaxel in previously untreated advanced non small cell lung cancer
Lung Cancer, 2009Co-Authors: Mark J Mckeage, Michael B Jameson, Martin Reck, Mark Rosenthal, David Gibbs, P N Mainwaring, Lutz Freitag, Richard Sullivan, Joachim Von PawelAbstract:This single-arm phase II study evaluated the tumor-vascular disrupting agent ASA404 (Vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800mg/m(2) plus standard therapy of carboplatin and paclitaxel in patients with advanced non-small cell lung cancer (NSCLC). This ASA404 dose is 50% higher than that used in previous phase II studies. Thirty patients with histologically confirmed stage IIIb or IV NSCLC previously untreated with chemotherapy received carboplatin AUC 6mg/mlmin plus paclitaxel 175mg/m(2) plus ASA404 1800mg/m(2) every 21 days for up to six cycles. The addition of ASA404 1800mg/m(2) to standard therapy produced little change in the systemic exposure of either total or free carboplatin or paclitaxel, and was generally well-tolerated, with no cardiac serious adverse events or clinically relevant ophthalmic abnormalities. The best overall tumor response was partial response, which was seen in 37.9% of patients by independent assessment and in 46.7% by investigator assessment. Stable disease was seen in 48.3% of patients by independent assessment and in 43.3% by investigator assessment. Median time to tumor progression was 5.5 months by investigator assessment and median survival was 14.9 months. The data from this trial corroborate findings from a recent randomized phase II trial, which suggested improvements in efficacy variables, including survival, when ASA404 1200mg/m(2) was added to standard therapy for advanced NSCLC. The manageable safety profile, lack of adverse pharmacokinetic interactions and efficacy outcomes seen in this single-arm study suggest that ASA404 1800mg/m(2) is a viable dose for future combination studies.
Martin Reck - One of the best experts on this subject based on the ideXlab platform.
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randomized phase iii placebo controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent Vadimezan asa404 in advanced non small cell lung cancer
Journal of Clinical Oncology, 2011Co-Authors: Primo N Lara, Jeanyves Douillard, Kazuhiko Nakagawa, Joachim Von Pawel, Mark J Mckeage, I Albert, Gyorgy Losonczy, Martin Reck, Dae Seog Heo, Xiaolin FanAbstract:Purpose This phase III trial was conducted to test whether the novel vascular disrupting agent ASA404 (Vadimezan), when combined with first-line platinum-based chemotherapy, improves survival in patients with advanced non–small-cell lung cancer (NSCLC) versus chemotherapy alone. Patients and Methods Patients with advanced stage IIIB or IV NSCLC, stratified by sex and tumor histology, were randomly assigned 1:1 to paclitaxel (200 mg/m2) and carboplatin (area under the curve, 6.0) with or without ASA404 (1,800 mg m2), given intravenously once every 3 weeks for six cycles followed by maintenance ASA404 or placebo. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results One thousand two hundred ninety-nine patients were randomly assigned. The trial was stopped for futility at interim analysis. At final analysis, there was no difference in OS seen between ASA404 (n = 649) and placebo (n = 650) arms: median OS was 13.4 a...
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randomized phase iii placebo controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent Vadimezan asa404 in advanced non small cell lung cancer
Journal of Clinical Oncology, 2011Co-Authors: Primo N Lara, Jeanyves Douillard, Kazuhiko Nakagawa, Mark J Mckeage, I Albert, Gyorgy Losonczy, Martin Reck, Joachim Von Pawel, Abderrahim Fandi, Giorgio V ScagliottiAbstract:PURPOSE: This phase III trial was conducted to test whether the novel vascular disrupting agent ASA404 (Vadimezan), when combined with first-line platinum-based chemotherapy, improves survival in patients with advanced non-small-cell lung cancer (NSCLC) versus chemotherapy alone. PATIENTS AND METHODS: Patients with advanced stage IIIB or IV NSCLC, stratified by sex and tumor histology, were randomly assigned 1:1 to paclitaxel (200 mg/m(2)) and carboplatin (area under the curve, 6.0) with or without ASA404 (1,800 mg m(2)), given intravenously once every 3 weeks for six cycles followed by maintenance ASA404 or placebo. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: One thousand two hundred ninety-nine patients were randomly assigned. The trial was stopped for futility at interim analysis. At final analysis, there was no difference in OS seen between ASA404 (n = 649) and placebo (n = 650) arms: median OS was 13.4 and 12.7 months respectively (hazard ratio [HR], 1.01; 95% CI, 0.85 to 1.19; P = .535). Similarly, no OS difference was seen in the histologic (squamous or nonsquamous) and sex (male or female) strata. Median PFS was 5.5 months in both arms (HR, 1.04; P = .727), while ORR was 25% in both arms (P = 1.0). Overall rate of adverse events (AEs) was comparable between the ASA404 and placebo arms. Grade 4 neutropenia (27% v 19%) and infusion site pain (10% v 0.5%) were reported more frequently in the ASA404 arm. CONCLUSION: The addition of ASA404 to carboplatin and paclitaxel, although generally well tolerated, failed to improve frontline efficacy in advanced NSCLC.
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phase ii study of asa404 Vadimezan 5 6 dimethylxanthenone 4 acetic acid dmxaa 1800 mg m2 combined with carboplatin and paclitaxel in previously untreated advanced non small cell lung cancer
Lung Cancer, 2009Co-Authors: Mark J Mckeage, Michael B Jameson, Martin Reck, Mark Rosenthal, David Gibbs, P N Mainwaring, Lutz Freitag, Richard Sullivan, Joachim Von PawelAbstract:This single-arm phase II study evaluated the tumor-vascular disrupting agent ASA404 (Vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800mg/m(2) plus standard therapy of carboplatin and paclitaxel in patients with advanced non-small cell lung cancer (NSCLC). This ASA404 dose is 50% higher than that used in previous phase II studies. Thirty patients with histologically confirmed stage IIIb or IV NSCLC previously untreated with chemotherapy received carboplatin AUC 6mg/mlmin plus paclitaxel 175mg/m(2) plus ASA404 1800mg/m(2) every 21 days for up to six cycles. The addition of ASA404 1800mg/m(2) to standard therapy produced little change in the systemic exposure of either total or free carboplatin or paclitaxel, and was generally well-tolerated, with no cardiac serious adverse events or clinically relevant ophthalmic abnormalities. The best overall tumor response was partial response, which was seen in 37.9% of patients by independent assessment and in 46.7% by investigator assessment. Stable disease was seen in 48.3% of patients by independent assessment and in 43.3% by investigator assessment. Median time to tumor progression was 5.5 months by investigator assessment and median survival was 14.9 months. The data from this trial corroborate findings from a recent randomized phase II trial, which suggested improvements in efficacy variables, including survival, when ASA404 1200mg/m(2) was added to standard therapy for advanced NSCLC. The manageable safety profile, lack of adverse pharmacokinetic interactions and efficacy outcomes seen in this single-arm study suggest that ASA404 1800mg/m(2) is a viable dose for future combination studies.
Joachim Von Pawel - One of the best experts on this subject based on the ideXlab platform.
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randomized phase iii placebo controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent Vadimezan asa404 in advanced non small cell lung cancer
Journal of Clinical Oncology, 2011Co-Authors: Primo N Lara, Jeanyves Douillard, Kazuhiko Nakagawa, Joachim Von Pawel, Mark J Mckeage, I Albert, Gyorgy Losonczy, Martin Reck, Dae Seog Heo, Xiaolin FanAbstract:Purpose This phase III trial was conducted to test whether the novel vascular disrupting agent ASA404 (Vadimezan), when combined with first-line platinum-based chemotherapy, improves survival in patients with advanced non–small-cell lung cancer (NSCLC) versus chemotherapy alone. Patients and Methods Patients with advanced stage IIIB or IV NSCLC, stratified by sex and tumor histology, were randomly assigned 1:1 to paclitaxel (200 mg/m2) and carboplatin (area under the curve, 6.0) with or without ASA404 (1,800 mg m2), given intravenously once every 3 weeks for six cycles followed by maintenance ASA404 or placebo. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results One thousand two hundred ninety-nine patients were randomly assigned. The trial was stopped for futility at interim analysis. At final analysis, there was no difference in OS seen between ASA404 (n = 649) and placebo (n = 650) arms: median OS was 13.4 a...
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phase ii study of asa404 Vadimezan 5 6 dimethylxanthenone 4 acetic acid dmxaa 1800 mg m2 combined with carboplatin and paclitaxel in previously untreated advanced non small cell lung cancer
Lung Cancer, 2009Co-Authors: Mark J Mckeage, Michael B Jameson, Martin Reck, Mark Rosenthal, David Gibbs, P N Mainwaring, Lutz Freitag, Richard Sullivan, Joachim Von PawelAbstract:This single-arm phase II study evaluated the tumor-vascular disrupting agent ASA404 (Vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800mg/m(2) plus standard therapy of carboplatin and paclitaxel in patients with advanced non-small cell lung cancer (NSCLC). This ASA404 dose is 50% higher than that used in previous phase II studies. Thirty patients with histologically confirmed stage IIIb or IV NSCLC previously untreated with chemotherapy received carboplatin AUC 6mg/mlmin plus paclitaxel 175mg/m(2) plus ASA404 1800mg/m(2) every 21 days for up to six cycles. The addition of ASA404 1800mg/m(2) to standard therapy produced little change in the systemic exposure of either total or free carboplatin or paclitaxel, and was generally well-tolerated, with no cardiac serious adverse events or clinically relevant ophthalmic abnormalities. The best overall tumor response was partial response, which was seen in 37.9% of patients by independent assessment and in 46.7% by investigator assessment. Stable disease was seen in 48.3% of patients by independent assessment and in 43.3% by investigator assessment. Median time to tumor progression was 5.5 months by investigator assessment and median survival was 14.9 months. The data from this trial corroborate findings from a recent randomized phase II trial, which suggested improvements in efficacy variables, including survival, when ASA404 1200mg/m(2) was added to standard therapy for advanced NSCLC. The manageable safety profile, lack of adverse pharmacokinetic interactions and efficacy outcomes seen in this single-arm study suggest that ASA404 1800mg/m(2) is a viable dose for future combination studies.
Primo N Lara - One of the best experts on this subject based on the ideXlab platform.
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randomized phase iii placebo controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent Vadimezan asa404 in advanced non small cell lung cancer
Journal of Clinical Oncology, 2011Co-Authors: Primo N Lara, Jeanyves Douillard, Kazuhiko Nakagawa, Joachim Von Pawel, Mark J Mckeage, I Albert, Gyorgy Losonczy, Martin Reck, Dae Seog Heo, Xiaolin FanAbstract:Purpose This phase III trial was conducted to test whether the novel vascular disrupting agent ASA404 (Vadimezan), when combined with first-line platinum-based chemotherapy, improves survival in patients with advanced non–small-cell lung cancer (NSCLC) versus chemotherapy alone. Patients and Methods Patients with advanced stage IIIB or IV NSCLC, stratified by sex and tumor histology, were randomly assigned 1:1 to paclitaxel (200 mg/m2) and carboplatin (area under the curve, 6.0) with or without ASA404 (1,800 mg m2), given intravenously once every 3 weeks for six cycles followed by maintenance ASA404 or placebo. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results One thousand two hundred ninety-nine patients were randomly assigned. The trial was stopped for futility at interim analysis. At final analysis, there was no difference in OS seen between ASA404 (n = 649) and placebo (n = 650) arms: median OS was 13.4 a...
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randomized phase iii placebo controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent Vadimezan asa404 in advanced non small cell lung cancer
Journal of Clinical Oncology, 2011Co-Authors: Primo N Lara, Jeanyves Douillard, Kazuhiko Nakagawa, Mark J Mckeage, I Albert, Gyorgy Losonczy, Martin Reck, Joachim Von Pawel, Abderrahim Fandi, Giorgio V ScagliottiAbstract:PURPOSE: This phase III trial was conducted to test whether the novel vascular disrupting agent ASA404 (Vadimezan), when combined with first-line platinum-based chemotherapy, improves survival in patients with advanced non-small-cell lung cancer (NSCLC) versus chemotherapy alone. PATIENTS AND METHODS: Patients with advanced stage IIIB or IV NSCLC, stratified by sex and tumor histology, were randomly assigned 1:1 to paclitaxel (200 mg/m(2)) and carboplatin (area under the curve, 6.0) with or without ASA404 (1,800 mg m(2)), given intravenously once every 3 weeks for six cycles followed by maintenance ASA404 or placebo. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: One thousand two hundred ninety-nine patients were randomly assigned. The trial was stopped for futility at interim analysis. At final analysis, there was no difference in OS seen between ASA404 (n = 649) and placebo (n = 650) arms: median OS was 13.4 and 12.7 months respectively (hazard ratio [HR], 1.01; 95% CI, 0.85 to 1.19; P = .535). Similarly, no OS difference was seen in the histologic (squamous or nonsquamous) and sex (male or female) strata. Median PFS was 5.5 months in both arms (HR, 1.04; P = .727), while ORR was 25% in both arms (P = 1.0). Overall rate of adverse events (AEs) was comparable between the ASA404 and placebo arms. Grade 4 neutropenia (27% v 19%) and infusion site pain (10% v 0.5%) were reported more frequently in the ASA404 arm. CONCLUSION: The addition of ASA404 to carboplatin and paclitaxel, although generally well tolerated, failed to improve frontline efficacy in advanced NSCLC.
