The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
C De Balincourt - One of the best experts on this subject based on the ideXlab platform.
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randomized phase iii trial of high dose intensity methotrexate vinblastine doxorubicin and cisplatin mvac chemotherapy and recombinant human granulocyte colony stimulating factor versus classic mvac in advanced urothelial tract tumors european organi
Journal of Clinical Oncology, 2001Co-Authors: Cora N Sternberg, P H M De Mulder, J H Schornagel, C Theodore, Sophie D Fossa, A Van Oosterom, F Witjes, M Spina, C J Van Groeningen, C De BalincourtAbstract:PURPOSE: This randomized trial evaluated antitumor activity of and survival asociated with high–dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). PATIENTS AND METHODS: A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). RESULTS: Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete Responses (CRs) (21%) and 55 partial Responses (PRs) (41%), for an Overall Response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an Overall Response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was .009; and for the Overall Response, it was .06. There was no statistically significant difference in survival (P =...
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Randomized Phase III Trial of High–Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European
Journal of Clinical Oncology, 2001Co-Authors: Cora N Sternberg, P H M De Mulder, J H Schornagel, C Theodore, Sophie D Fossa, A Van Oosterom, F Witjes, M Spina, C J Van Groeningen, C De BalincourtAbstract:PURPOSE: This randomized trial evaluated antitumor activity of and survival asociated with high–dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). PATIENTS AND METHODS: A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). RESULTS: Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete Responses (CRs) (21%) and 55 partial Responses (PRs) (41%), for an Overall Response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an Overall Response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was .009; and for the Overall Response, it was .06. There was no statistically significant difference in survival (P =...
Todd M Durell - One of the best experts on this subject based on the ideXlab platform.
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olanzapine fluoxetine combination in patients with treatment resistant depression rapid onset of therapeutic Response and its predictive value for subsequent Overall Response in a pooled analysis of 5 studies
The Journal of Clinical Psychiatry, 2010Co-Authors: Mauricio Tohen, Michael Case, Madhukar H Trivedi, Michael E Thase, Scott J Burke, Todd M DurellAbstract:OBJECTIVE: To characterize Response profiles of olanzapine/fluoxetine combination therapy in treatment-resistant depression (TRD) and to investigate predictive relationships of early improvement with olanzapine/fluoxetine combination for subsequent Response/remission during the acute phase of treatment. METHOD: Results were pooled from 5 outpatient studies comparing oral olanzapine/fluoxetine combination, fluoxetine, or olanzapine for a maximum of 8 weeks in patients with TRD who had at least 1 historical antidepressant treatment failure during the current episode and who failed a prospective antidepressant therapy during the study lead-in period. Mean Montgomery-Asberg Depression Rating Scale (MADRS) total and core mood items scores from the 8-week evaluation period were compared across treatment groups. Positive and negative predictive values (PPVs, NPVs) were computed from olanzapine/fluoxetine combination-treated patients demonstrating Response and remission based on whether they demonstrated early improvement. RESULTS: Mean olanzapine/fluoxetine combination MADRS score reductions were significantly greater than fluoxetine by week 0.5 and olanzapine by week 1. Significantly more olanzapine/fluoxetine combination patients demonstrated MADRS onset of Response compared with fluoxetine and olanzapine patients (P < .001 for both MADRS total and core mood items). In olanzapine/fluoxetine combination patients, 38.1% exhibited MADRS total score Response versus 26.9% of fluoxetine patients (P < .001) and 22.2% of olanzapine patients (P < .001). NPVs for MADRS total and core mood items Response and remission ranged from 85.7% to 92.1%; PPVs ranged from 29.9% to 45.1%. CONCLUSIONS: Olanzapine/fluoxetine combination is superior to fluoxetine and olanzapine in producing early improvement in patients with TRD. The absence of early improvement is highly predictive for Overall Response failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00035321.
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Olanzapine/fluoxetine combination in patients with treatment-resistant depression: rapid onset of therapeutic Response and its predictive value for subsequent Overall Response in a pooled analysis of 5 studies.
The Journal of Clinical Psychiatry, 2010Co-Authors: Mauricio Tohen, Michael Case, Madhukar H Trivedi, Michael E Thase, Scott J Burke, Todd M DurellAbstract:OBJECTIVE: To characterize Response profiles of olanzapine/fluoxetine combination therapy in treatment-resistant depression (TRD) and to investigate predictive relationships of early improvement with olanzapine/fluoxetine combination for subsequent Response/remission during the acute phase of treatment. METHOD: Results were pooled from 5 outpatient studies comparing oral olanzapine/fluoxetine combination, fluoxetine, or olanzapine for a maximum of 8 weeks in patients with TRD who had at least 1 historical antidepressant treatment failure during the current episode and who failed a prospective antidepressant therapy during the study lead-in period. Mean Montgomery-Asberg Depression Rating Scale (MADRS) total and core mood items scores from the 8-week evaluation period were compared across treatment groups. Positive and negative predictive values (PPVs, NPVs) were computed from olanzapine/fluoxetine combination-treated patients demonstrating Response and remission based on whether they demonstrated early improvement. RESULTS: Mean olanzapine/fluoxetine combination MADRS score reductions were significantly greater than fluoxetine by week 0.5 and olanzapine by week 1. Significantly more olanzapine/fluoxetine combination patients demonstrated MADRS onset of Response compared with fluoxetine and olanzapine patients (P < .001 for both MADRS total and core mood items). In olanzapine/fluoxetine combination patients, 38.1% exhibited MADRS total score Response versus 26.9% of fluoxetine patients (P < .001) and 22.2% of olanzapine patients (P < .001). NPVs for MADRS total and core mood items Response and remission ranged from 85.7% to 92.1%; PPVs ranged from 29.9% to 45.1%. CONCLUSIONS: Olanzapine/fluoxetine combination is superior to fluoxetine and olanzapine in producing early improvement in patients with TRD. The absence of early improvement is highly predictive for Overall Response failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00035321.
Richard Pazdur - One of the best experts on this subject based on the ideXlab platform.
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Overall Response rate progression free survival and Overall survival with targeted and standard therapies in advanced non small cell lung cancer us food and drug administration trial level and patient level analyses
Journal of Clinical Oncology, 2015Co-Authors: Gideon M. Blumenthal, Rajeshwari Sridhara, Stella W Karuri, Hui Zhang, Lijun Zhang, Sean Khozin, Dickran Kazandjian, Shenghui Tang, Patricia Keegan, Richard PazdurAbstract:Purpose To conduct analyses exploring trial-level and patient-level associations between Overall Response rate (ORR), progression-free survival (PFS), and Overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective Response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level respond...
Gideon M. Blumenthal - One of the best experts on this subject based on the ideXlab platform.
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Time dependent pharmacokinetics of pembrolizumab in patients with solid tumor and its correlation with best Overall Response
Journal of Pharmacokinetics and Pharmacodynamics, 2017Co-Authors: Hongshan Li, Jingyu Yu, Sriram Subramaniam, Hong Zhao, Gideon M. Blumenthal, David C. Turner, Claire Li, Malidi Ahamadi, Rik Greef, Manash ChatterjeeAbstract:Pembrolizumab is a monoclonal antibody that targets the programmed death-1 receptor to induce immune-mediated clearance (CL) of tumor cells. Originally approved by the US Food and Drug Administration in 2014 for treating patients with unresectable or metastatic melanoma, pembrolizumab is now also used to treat patients with non-small-cell lung cancer, classical Hodgkin lymphoma, head and neck cancer, and urothelial cancer. This paper describes the recently identified feature of pembrolizumab pharmacokinetics, the time-dependent or time-varying CL. Overall results indicate that CL decreases over the treatment period of a typical patient in a pattern well described by a sigmoidal function of time with three parameters: the maximum proportion change in CL from baseline (approximately I_max or exactly e^Imax − 1), the time to reach I_max/2 (TI_50), and a Hill coefficient. Best Overall Response per Response evaluation criteria in solid tumor category was found to be associated with the magnitude of I_max.
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Overall Response rate progression free survival and Overall survival with targeted and standard therapies in advanced non small cell lung cancer us food and drug administration trial level and patient level analyses
Journal of Clinical Oncology, 2015Co-Authors: Gideon M. Blumenthal, Rajeshwari Sridhara, Stella W Karuri, Hui Zhang, Lijun Zhang, Sean Khozin, Dickran Kazandjian, Shenghui Tang, Patricia Keegan, Richard PazdurAbstract:Purpose To conduct analyses exploring trial-level and patient-level associations between Overall Response rate (ORR), progression-free survival (PFS), and Overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective Response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level respond...
Cora N Sternberg - One of the best experts on this subject based on the ideXlab platform.
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randomized phase iii trial of high dose intensity methotrexate vinblastine doxorubicin and cisplatin mvac chemotherapy and recombinant human granulocyte colony stimulating factor versus classic mvac in advanced urothelial tract tumors european organi
Journal of Clinical Oncology, 2001Co-Authors: Cora N Sternberg, P H M De Mulder, J H Schornagel, C Theodore, Sophie D Fossa, A Van Oosterom, F Witjes, M Spina, C J Van Groeningen, C De BalincourtAbstract:PURPOSE: This randomized trial evaluated antitumor activity of and survival asociated with high–dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). PATIENTS AND METHODS: A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). RESULTS: Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete Responses (CRs) (21%) and 55 partial Responses (PRs) (41%), for an Overall Response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an Overall Response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was .009; and for the Overall Response, it was .06. There was no statistically significant difference in survival (P =...
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Randomized Phase III Trial of High–Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European
Journal of Clinical Oncology, 2001Co-Authors: Cora N Sternberg, P H M De Mulder, J H Schornagel, C Theodore, Sophie D Fossa, A Van Oosterom, F Witjes, M Spina, C J Van Groeningen, C De BalincourtAbstract:PURPOSE: This randomized trial evaluated antitumor activity of and survival asociated with high–dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). PATIENTS AND METHODS: A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). RESULTS: Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete Responses (CRs) (21%) and 55 partial Responses (PRs) (41%), for an Overall Response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an Overall Response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was .009; and for the Overall Response, it was .06. There was no statistically significant difference in survival (P =...
