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Jean-yves Douillard - One of the best experts on this subject based on the ideXlab platform.
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adjuvant cisplatin and Vinorelbine for completely resected non small cell lung cancer subgroup analysis of the lung adjuvant cisplatin evaluation
Journal of Thoracic Oncology, 2010Co-Authors: Jean-yves Douillard, Helene Tribodet, Delphine Aubert, Frances A Shepherd, Rafael Rosell, Keyue Ding, Annesophie Veillard, Lesley Seymour, Thierry Le Chevalier, Stephen G SpiroAbstract:Background To evaluate the impact of adjuvant cisplatin-Vinorelbine in completely resected non-small cell lung cancer and identify patients likely to benefit from this regimen in the Lung Adjuvant Cisplatin Evaluation (LACE) database. The overall LACE meta-analysis showed survival benefit with cisplatin-based adjuvant chemotherapy (5-year survival benefit of 5.4%, hazard ratio [HR] 0.89, p = 0.004). Subgroup analysis for the cisplatin-Vinorelbine regimen was prespecified in the LACE statistical analysis plan. Patients randomized to cisplatin-Vinorelbine or observation were the largest subgroup (41%) and the most homogeneous in terms of drug doses and eligibility. Patients and Methods The LACE-Vinorelbine cohort included trials evaluating cisplatin-Vinorelbine versus observation. Overall survival was the primary end point. Other studies randomizing patients to other chemotherapy or observation (LACE-other) were also evaluated. Results The LACE-Vinorelbine cohort included 1888 patients from four studies (Adjuvant Navelbine International Trialist Association, Big Lung Trial, International Adjuvant Lung Cancer Trial, and National Cancer Institute of Canada Clinical Trials Group JBR.10). Baseline characteristics were similar to the LACE-other but had fewer patients with stage IA (2% versus 11%). Survival improvement at 5 years was 8.9% with cisplatin-Vinorelbine versus observation (HR 0.80, 95% confidence interval: 0.70–0.91, p p = 0.02; benefit at 5 years: 14.7% [stage III], 11.6% [stage II], and 1.8% [stage I]). Similar benefits were seen for disease-free survival (HR 0.75 [0.67–0.85, p p = 0.04). Conclusion In subgroup analyses, adjuvant cisplatin-Vinorelbine provides a superior survival benefit and can be recommended in completely resected stages II and III non-small cell lung cancer.
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long term analysis of survival in the european randomized trial comparing Vinorelbine cisplatin to vindesine cisplatin and Vinorelbine alone in advanced non small cell lung cancer
Oncologist, 2001Co-Authors: Le T Chevalier, J.l. Pujol, Jean-yves Douillard, D Brisgand, J C Soria, P Ruffie, V Aberola, S. CigolariAbstract:In the period 1989-1991, 612 patients with inoperable stage IIIA/B and IV non-small cell lung cancer (NSCLC) were randomized in a phase III trial comparing three chemotherapy regimens. Survival data at five and six years of follow-up confirm the overall benefit of treatment with a combination of Vinorelbine and cisplatin compared to vindesine plus cisplatin or Vinorelbine alone. Of the 612 patients randomized at the start of the study, 17 have survived beyond five years. Of these patients, eight had entered the trial with metastatic disease. Multivariate analysis to detect prognostic factors suggested a possible interaction between the effect of having cisplatin in the chemotherapy received and baseline performance status. Subgroup analysis subsequently confirmed that the survival benefit of the Vinorelbine plus chemotherapy regimen is evident only in patients with initial World Health Organization performance status (PS) of 0-1. Among these patients, the one-year survival rate is 38% for the Vinorelbine/cisplatin arm, 29% for vindesine/cisplatin and 34% for Vinorelbine alone. The corresponding figures for median survival are 43, 33 and 36 weeks. Among inoperable NSCLC patients with a PS of 2, who appear from this trial not to have benefited from the presence of cisplatin in their chemotherapy, use of single agent Vinorelbine is an appropriate treatment option. The Oncologist 2001;6(suppl 1):8-11
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A three-arm trial of Vinorelbine (Navelbine) plus cisplatin, vindesine plus cisplatin, and single-agent Vinorelbine in the treatment of non-small cell lung cancer: an expanded analysis.
Seminars in Oncology, 1994Co-Authors: Le Chevalier T, J.l. Pujol, Jean-yves Douillard, Alberola, A. Monnier, A. Riviere, Lianes P, Chomy P, S. Cigolari, F. BessonAbstract:Phase II studies have demonstrated that Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) alone or in combination with cisplatin has promising activity against non-small cell lung cancer (NSCLC). On the basis of these preliminary trials, a phase III study was designed to compare intravenous Vinorelbine (30 mg/m2 weekly) plus cisplatin (120 mg/m2 on day 1 and day 29 and then every 6 weeks) with vindesine (3 mg/m2 weekly for 6 weeks and then every 2 weeks) plus cisplatin, and to evaluate whether the best of these regimens afforded a survival benefit compared with intravenous Vinorelbine alone, an outpatient regimen. This report presents an expanded analysis of data from this previously published study. Six hundred twelve patients were enrolled in this trial: 206 in the Vinorelbine plus cisplatin arm, 200 in the vindesine plus cisplatin group, and 206 in the single-agent Vinorelbine arm. The Vinorelbine plus cisplatin regimen was superior to the other two arms of the study in objective response rate (30% v 19% for vindesine plus cisplatin [P = .02] and 14% for Vinorelbine alone [P = .001]), median survival duration (40 weeks v 32 weeks for vindesine plus cisplatin and 31 weeks for Vinorelbine alone), and 1-year survival rate (35% v 27% for vindesine plus cisplatin and 30% for Vinorelbine alone). An adjusted log-rank test provided a significant advantage for Vinorelbine plus cisplatin when compared with vindesine plus cisplatin (P = .04) and with Vinorelbine alone (P = .02). The major difference in survival between the two cisplatin-containing regimens occurred in patients with metastatic (stage IV) NSCLC. The incidence of granulocytopenia was significantly higher in the Vinorelbine plus cisplatin arm compared with the other two treatment groups, but neurotoxicity was significantly more frequent in the vindesine plus cisplatin group. The results of this study indicate that the combination of Vinorelbine plus cisplatin is a viable treatment option for patients with NSCLC and may provide advantages compared with other commonly used regimens.
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A three-arm trial of Vinorelbine (Navelbine) plus cisplatin, vindesine plus cisplatin, and single-agent Vinorelbine in the treatment of non-small cell lung cancer: an expanded analysis.
Seminars in oncology, 1994Co-Authors: T Le Chevalier, J.l. Pujol, Jean-yves Douillard, A. Monnier, A. Riviere, S. Cigolari, V Alberola, P Lianes, P Chomy, F. BessonAbstract:Phase II studies have demonstrated that Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) alone or in combination with cisplatin has promising activity against non-small cell lung cancer (NSCLC). On the basis of these preliminary trials, a phase III study was designed to compare intravenous Vinorelbine (30 mg/m2 weekly) plus cisplatin (120 mg/m2 on day 1 and day 29 and then every 6 weeks) with vindesine (3 mg/m2 weekly for 6 weeks and then every 2 weeks) plus cisplatin, and to evaluate whether the best of these regimens afforded a survival benefit compared with intravenous Vinorelbine alone, an outpatient regimen. This report presents an expanded analysis of data from this previously published study. Six hundred twelve patients were enrolled in this trial: 206 in the Vinorelbine plus cisplatin arm, 200 in the vindesine plus cisplatin group, and 206 in the single-agent Vinorelbine arm. The Vinorelbine plus cisplatin regimen was superior to the other two arms of the study in objective response rate (30% v 19% for vindesine plus cisplatin [P = .02] and 14% for Vinorelbine alone [P = .001]), median survival duration (40 weeks v 32 weeks for vindesine plus cisplatin and 31 weeks for Vinorelbine alone), and 1-year survival rate (35% v 27% for vindesine plus cisplatin and 30% for Vinorelbine alone). An adjusted log-rank test provided a significant advantage for Vinorelbine plus cisplatin when compared with vindesine plus cisplatin (P = .04) and with Vinorelbine alone (P = .02). The major difference in survival between the two cisplatin-containing regimens occurred in patients with metastatic (stage IV) NSCLC. The incidence of granulocytopenia was significantly higher in the Vinorelbine plus cisplatin arm compared with the other two treatment groups, but neurotoxicity was significantly more frequent in the vindesine plus cisplatin group. The results of this study indicate that the combination of Vinorelbine plus cisplatin is a viable treatment option for patients with NSCLC and may provide advantages compared with other commonly used regimens.
P. Quintana - One of the best experts on this subject based on the ideXlab platform.
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Tolerability and incidence of infusion site reactions with emulsion formulation of Vinorelbine (ANX-530) compared to Vinorelbine solution
Journal of Clinical Oncology, 2008Co-Authors: J. Schupp, L. P. Lopez, J. M. Robbins, L. Arboit, H. Requejo, G. Arroyo, C. Blajman, Luis Fein, M. Chacón, P. QuintanaAbstract:13549 Background: ANX-530 is an oil-in-water emulsion formulation of Vinorelbine that has demonstrated less vein irritation, equivalent antitumor activity, and similar pharmacokinetic profiles to Vinorelbine solution in preclinical studies. Pharmacokinetic equivalence to Vinorelbine solution was recently reported in patients treated with each agent in a randomized clinical study. Methods: Thirty-one patients were enrolled in this single-dose 2-period crossover study, randomized for sequence. Patients had an advanced cancer potentially sensitive to Vinorelbine after failure of standard treatments. Patients were randomly assigned to receive a single intravenous dose of either ANX-530 or Vinorelbine in the first study period, then 1 week later, were crossed over to the other Vinorelbine formulation. Both drugs were infused over 10 minutes at a dose of 30 mg/m2 using a calibrated syringe pump. Adverse events were analyzed by a logistic regression model with factors for treatment (ANX-530 vs. Vinorelbine), per...
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Pharmacokinetic equivalence observed between an emulsion formulation of Vinorelbine (ANX-530) and Vinorelbine solution in a clinical study of patients with advanced cancer.
Cancer Research, 2008Co-Authors: H. Requejo, L. Arboit, G. Arroyo, C. Blajman, Luis Fein, M. Chacón, P. Quintana, Mark J. Cantwell, Daryl Smith, Jennifer EllisAbstract:207 Background: An oil-in-water emulsion formulation of Vinorelbine, ANX-530, was evaluated for bioequivalence with Vinorelbine solution in a multi-center, open label, randomized, crossover study. Vinorelbine is a semisynthetic derivative of vinblastine and is approved for use in patients with non-small cell lung cancer. However, Vinorelbine solution is a vesicant and venous irritant, and these adverse effects can limit its tolerability. Preclinical studies demonstrated less venous irritation, decreased hemolysis, equivalent antitumor activity, and similar pharmacokinetic profiles for ANX-530 and Vinorelbine solution. Methods: A clinical trial was performed to determine the bioequivalence of ANX-530 and Vinorelbine solution. The bioequivalence study enrolled cancer patients in a standard 2-period crossover design randomized for sequence. Patients were eligible with an advanced cancer potentially sensitive to Vinorelbine after failure of standard treatments for the tumor. Patients requiring concomitant chemotherapeutic agents or having prior Vinorelbine or mitomycin treatment were excluded. The patients were randomly assigned to receive a single intravenous dose of either ANX-530 or Vinorelbine solution in the first study period, then one week later, crossover to the other Vinorelbine formulation. All drug administrations were given as 10 minute infusions at a dose of 30 mg/m2. Blood samples for pharmacokinetic analysis were collected predose, 10, 20, and 40 min, and 1, 3, 6, 24, 48, 72, and 144 hr after the end of the infusion. Hematology, serum chemistry, and adverse event reporting were performed throughout the study period. The primary endpoint of pharmacokinetic equivalence was assessed by analysis of variance comparison of the log transformed values of Vinorelbine area under the curve (AUC) and maximum plasma concentration (Cmax). Results: A total of 31 patients were enrolled. The median age was 60 years (range 31-83) and 26 patients (84%) were female. 20 patients (64%) had breast cancer, 3 patients (10%) had lung cancer, and 8 patients (26%) had other cancer types. All patients had been previously treated with chemotherapy. All 31 patients received both formulations and had adequate pharmacokinetic data. The geometric mean ratio percentage (90% confidence interval) of Cmax was 104% (87% - 123%), of AUClast was 106% (99% - 112%), and of AUCinfinity was 106% (100% - 112%). Complete safety results will be presented. Conclusion: The 90% confidence intervals of the ratio for Cmax and AUC parameters were within the 80-125% predefined interval for bioequivalence based on FDA guidelines. As such, pharmacokinetic equivalence was observed between ANX-530 and Vinorelbine solution.
F. Besson - One of the best experts on this subject based on the ideXlab platform.
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A three-arm trial of Vinorelbine (Navelbine) plus cisplatin, vindesine plus cisplatin, and single-agent Vinorelbine in the treatment of non-small cell lung cancer: an expanded analysis.
Seminars in Oncology, 1994Co-Authors: Le Chevalier T, J.l. Pujol, Jean-yves Douillard, Alberola, A. Monnier, A. Riviere, Lianes P, Chomy P, S. Cigolari, F. BessonAbstract:Phase II studies have demonstrated that Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) alone or in combination with cisplatin has promising activity against non-small cell lung cancer (NSCLC). On the basis of these preliminary trials, a phase III study was designed to compare intravenous Vinorelbine (30 mg/m2 weekly) plus cisplatin (120 mg/m2 on day 1 and day 29 and then every 6 weeks) with vindesine (3 mg/m2 weekly for 6 weeks and then every 2 weeks) plus cisplatin, and to evaluate whether the best of these regimens afforded a survival benefit compared with intravenous Vinorelbine alone, an outpatient regimen. This report presents an expanded analysis of data from this previously published study. Six hundred twelve patients were enrolled in this trial: 206 in the Vinorelbine plus cisplatin arm, 200 in the vindesine plus cisplatin group, and 206 in the single-agent Vinorelbine arm. The Vinorelbine plus cisplatin regimen was superior to the other two arms of the study in objective response rate (30% v 19% for vindesine plus cisplatin [P = .02] and 14% for Vinorelbine alone [P = .001]), median survival duration (40 weeks v 32 weeks for vindesine plus cisplatin and 31 weeks for Vinorelbine alone), and 1-year survival rate (35% v 27% for vindesine plus cisplatin and 30% for Vinorelbine alone). An adjusted log-rank test provided a significant advantage for Vinorelbine plus cisplatin when compared with vindesine plus cisplatin (P = .04) and with Vinorelbine alone (P = .02). The major difference in survival between the two cisplatin-containing regimens occurred in patients with metastatic (stage IV) NSCLC. The incidence of granulocytopenia was significantly higher in the Vinorelbine plus cisplatin arm compared with the other two treatment groups, but neurotoxicity was significantly more frequent in the vindesine plus cisplatin group. The results of this study indicate that the combination of Vinorelbine plus cisplatin is a viable treatment option for patients with NSCLC and may provide advantages compared with other commonly used regimens.
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A three-arm trial of Vinorelbine (Navelbine) plus cisplatin, vindesine plus cisplatin, and single-agent Vinorelbine in the treatment of non-small cell lung cancer: an expanded analysis.
Seminars in oncology, 1994Co-Authors: T Le Chevalier, J.l. Pujol, Jean-yves Douillard, A. Monnier, A. Riviere, S. Cigolari, V Alberola, P Lianes, P Chomy, F. BessonAbstract:Phase II studies have demonstrated that Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) alone or in combination with cisplatin has promising activity against non-small cell lung cancer (NSCLC). On the basis of these preliminary trials, a phase III study was designed to compare intravenous Vinorelbine (30 mg/m2 weekly) plus cisplatin (120 mg/m2 on day 1 and day 29 and then every 6 weeks) with vindesine (3 mg/m2 weekly for 6 weeks and then every 2 weeks) plus cisplatin, and to evaluate whether the best of these regimens afforded a survival benefit compared with intravenous Vinorelbine alone, an outpatient regimen. This report presents an expanded analysis of data from this previously published study. Six hundred twelve patients were enrolled in this trial: 206 in the Vinorelbine plus cisplatin arm, 200 in the vindesine plus cisplatin group, and 206 in the single-agent Vinorelbine arm. The Vinorelbine plus cisplatin regimen was superior to the other two arms of the study in objective response rate (30% v 19% for vindesine plus cisplatin [P = .02] and 14% for Vinorelbine alone [P = .001]), median survival duration (40 weeks v 32 weeks for vindesine plus cisplatin and 31 weeks for Vinorelbine alone), and 1-year survival rate (35% v 27% for vindesine plus cisplatin and 30% for Vinorelbine alone). An adjusted log-rank test provided a significant advantage for Vinorelbine plus cisplatin when compared with vindesine plus cisplatin (P = .04) and with Vinorelbine alone (P = .02). The major difference in survival between the two cisplatin-containing regimens occurred in patients with metastatic (stage IV) NSCLC. The incidence of granulocytopenia was significantly higher in the Vinorelbine plus cisplatin arm compared with the other two treatment groups, but neurotoxicity was significantly more frequent in the vindesine plus cisplatin group. The results of this study indicate that the combination of Vinorelbine plus cisplatin is a viable treatment option for patients with NSCLC and may provide advantages compared with other commonly used regimens.
S. Cigolari - One of the best experts on this subject based on the ideXlab platform.
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long term analysis of survival in the european randomized trial comparing Vinorelbine cisplatin to vindesine cisplatin and Vinorelbine alone in advanced non small cell lung cancer
Oncologist, 2001Co-Authors: Le T Chevalier, J.l. Pujol, Jean-yves Douillard, D Brisgand, J C Soria, P Ruffie, V Aberola, S. CigolariAbstract:In the period 1989-1991, 612 patients with inoperable stage IIIA/B and IV non-small cell lung cancer (NSCLC) were randomized in a phase III trial comparing three chemotherapy regimens. Survival data at five and six years of follow-up confirm the overall benefit of treatment with a combination of Vinorelbine and cisplatin compared to vindesine plus cisplatin or Vinorelbine alone. Of the 612 patients randomized at the start of the study, 17 have survived beyond five years. Of these patients, eight had entered the trial with metastatic disease. Multivariate analysis to detect prognostic factors suggested a possible interaction between the effect of having cisplatin in the chemotherapy received and baseline performance status. Subgroup analysis subsequently confirmed that the survival benefit of the Vinorelbine plus chemotherapy regimen is evident only in patients with initial World Health Organization performance status (PS) of 0-1. Among these patients, the one-year survival rate is 38% for the Vinorelbine/cisplatin arm, 29% for vindesine/cisplatin and 34% for Vinorelbine alone. The corresponding figures for median survival are 43, 33 and 36 weeks. Among inoperable NSCLC patients with a PS of 2, who appear from this trial not to have benefited from the presence of cisplatin in their chemotherapy, use of single agent Vinorelbine is an appropriate treatment option. The Oncologist 2001;6(suppl 1):8-11
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A three-arm trial of Vinorelbine (Navelbine) plus cisplatin, vindesine plus cisplatin, and single-agent Vinorelbine in the treatment of non-small cell lung cancer: an expanded analysis.
Seminars in Oncology, 1994Co-Authors: Le Chevalier T, J.l. Pujol, Jean-yves Douillard, Alberola, A. Monnier, A. Riviere, Lianes P, Chomy P, S. Cigolari, F. BessonAbstract:Phase II studies have demonstrated that Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) alone or in combination with cisplatin has promising activity against non-small cell lung cancer (NSCLC). On the basis of these preliminary trials, a phase III study was designed to compare intravenous Vinorelbine (30 mg/m2 weekly) plus cisplatin (120 mg/m2 on day 1 and day 29 and then every 6 weeks) with vindesine (3 mg/m2 weekly for 6 weeks and then every 2 weeks) plus cisplatin, and to evaluate whether the best of these regimens afforded a survival benefit compared with intravenous Vinorelbine alone, an outpatient regimen. This report presents an expanded analysis of data from this previously published study. Six hundred twelve patients were enrolled in this trial: 206 in the Vinorelbine plus cisplatin arm, 200 in the vindesine plus cisplatin group, and 206 in the single-agent Vinorelbine arm. The Vinorelbine plus cisplatin regimen was superior to the other two arms of the study in objective response rate (30% v 19% for vindesine plus cisplatin [P = .02] and 14% for Vinorelbine alone [P = .001]), median survival duration (40 weeks v 32 weeks for vindesine plus cisplatin and 31 weeks for Vinorelbine alone), and 1-year survival rate (35% v 27% for vindesine plus cisplatin and 30% for Vinorelbine alone). An adjusted log-rank test provided a significant advantage for Vinorelbine plus cisplatin when compared with vindesine plus cisplatin (P = .04) and with Vinorelbine alone (P = .02). The major difference in survival between the two cisplatin-containing regimens occurred in patients with metastatic (stage IV) NSCLC. The incidence of granulocytopenia was significantly higher in the Vinorelbine plus cisplatin arm compared with the other two treatment groups, but neurotoxicity was significantly more frequent in the vindesine plus cisplatin group. The results of this study indicate that the combination of Vinorelbine plus cisplatin is a viable treatment option for patients with NSCLC and may provide advantages compared with other commonly used regimens.
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A three-arm trial of Vinorelbine (Navelbine) plus cisplatin, vindesine plus cisplatin, and single-agent Vinorelbine in the treatment of non-small cell lung cancer: an expanded analysis.
Seminars in oncology, 1994Co-Authors: T Le Chevalier, J.l. Pujol, Jean-yves Douillard, A. Monnier, A. Riviere, S. Cigolari, V Alberola, P Lianes, P Chomy, F. BessonAbstract:Phase II studies have demonstrated that Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) alone or in combination with cisplatin has promising activity against non-small cell lung cancer (NSCLC). On the basis of these preliminary trials, a phase III study was designed to compare intravenous Vinorelbine (30 mg/m2 weekly) plus cisplatin (120 mg/m2 on day 1 and day 29 and then every 6 weeks) with vindesine (3 mg/m2 weekly for 6 weeks and then every 2 weeks) plus cisplatin, and to evaluate whether the best of these regimens afforded a survival benefit compared with intravenous Vinorelbine alone, an outpatient regimen. This report presents an expanded analysis of data from this previously published study. Six hundred twelve patients were enrolled in this trial: 206 in the Vinorelbine plus cisplatin arm, 200 in the vindesine plus cisplatin group, and 206 in the single-agent Vinorelbine arm. The Vinorelbine plus cisplatin regimen was superior to the other two arms of the study in objective response rate (30% v 19% for vindesine plus cisplatin [P = .02] and 14% for Vinorelbine alone [P = .001]), median survival duration (40 weeks v 32 weeks for vindesine plus cisplatin and 31 weeks for Vinorelbine alone), and 1-year survival rate (35% v 27% for vindesine plus cisplatin and 30% for Vinorelbine alone). An adjusted log-rank test provided a significant advantage for Vinorelbine plus cisplatin when compared with vindesine plus cisplatin (P = .04) and with Vinorelbine alone (P = .02). The major difference in survival between the two cisplatin-containing regimens occurred in patients with metastatic (stage IV) NSCLC. The incidence of granulocytopenia was significantly higher in the Vinorelbine plus cisplatin arm compared with the other two treatment groups, but neurotoxicity was significantly more frequent in the vindesine plus cisplatin group. The results of this study indicate that the combination of Vinorelbine plus cisplatin is a viable treatment option for patients with NSCLC and may provide advantages compared with other commonly used regimens.
H. Requejo - One of the best experts on this subject based on the ideXlab platform.
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Tolerability and incidence of infusion site reactions with emulsion formulation of Vinorelbine (ANX-530) compared to Vinorelbine solution
Journal of Clinical Oncology, 2008Co-Authors: J. Schupp, L. P. Lopez, J. M. Robbins, L. Arboit, H. Requejo, G. Arroyo, C. Blajman, Luis Fein, M. Chacón, P. QuintanaAbstract:13549 Background: ANX-530 is an oil-in-water emulsion formulation of Vinorelbine that has demonstrated less vein irritation, equivalent antitumor activity, and similar pharmacokinetic profiles to Vinorelbine solution in preclinical studies. Pharmacokinetic equivalence to Vinorelbine solution was recently reported in patients treated with each agent in a randomized clinical study. Methods: Thirty-one patients were enrolled in this single-dose 2-period crossover study, randomized for sequence. Patients had an advanced cancer potentially sensitive to Vinorelbine after failure of standard treatments. Patients were randomly assigned to receive a single intravenous dose of either ANX-530 or Vinorelbine in the first study period, then 1 week later, were crossed over to the other Vinorelbine formulation. Both drugs were infused over 10 minutes at a dose of 30 mg/m2 using a calibrated syringe pump. Adverse events were analyzed by a logistic regression model with factors for treatment (ANX-530 vs. Vinorelbine), per...
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Pharmacokinetic equivalence observed between an emulsion formulation of Vinorelbine (ANX-530) and Vinorelbine solution in a clinical study of patients with advanced cancer.
Cancer Research, 2008Co-Authors: H. Requejo, L. Arboit, G. Arroyo, C. Blajman, Luis Fein, M. Chacón, P. Quintana, Mark J. Cantwell, Daryl Smith, Jennifer EllisAbstract:207 Background: An oil-in-water emulsion formulation of Vinorelbine, ANX-530, was evaluated for bioequivalence with Vinorelbine solution in a multi-center, open label, randomized, crossover study. Vinorelbine is a semisynthetic derivative of vinblastine and is approved for use in patients with non-small cell lung cancer. However, Vinorelbine solution is a vesicant and venous irritant, and these adverse effects can limit its tolerability. Preclinical studies demonstrated less venous irritation, decreased hemolysis, equivalent antitumor activity, and similar pharmacokinetic profiles for ANX-530 and Vinorelbine solution. Methods: A clinical trial was performed to determine the bioequivalence of ANX-530 and Vinorelbine solution. The bioequivalence study enrolled cancer patients in a standard 2-period crossover design randomized for sequence. Patients were eligible with an advanced cancer potentially sensitive to Vinorelbine after failure of standard treatments for the tumor. Patients requiring concomitant chemotherapeutic agents or having prior Vinorelbine or mitomycin treatment were excluded. The patients were randomly assigned to receive a single intravenous dose of either ANX-530 or Vinorelbine solution in the first study period, then one week later, crossover to the other Vinorelbine formulation. All drug administrations were given as 10 minute infusions at a dose of 30 mg/m2. Blood samples for pharmacokinetic analysis were collected predose, 10, 20, and 40 min, and 1, 3, 6, 24, 48, 72, and 144 hr after the end of the infusion. Hematology, serum chemistry, and adverse event reporting were performed throughout the study period. The primary endpoint of pharmacokinetic equivalence was assessed by analysis of variance comparison of the log transformed values of Vinorelbine area under the curve (AUC) and maximum plasma concentration (Cmax). Results: A total of 31 patients were enrolled. The median age was 60 years (range 31-83) and 26 patients (84%) were female. 20 patients (64%) had breast cancer, 3 patients (10%) had lung cancer, and 8 patients (26%) had other cancer types. All patients had been previously treated with chemotherapy. All 31 patients received both formulations and had adequate pharmacokinetic data. The geometric mean ratio percentage (90% confidence interval) of Cmax was 104% (87% - 123%), of AUClast was 106% (99% - 112%), and of AUCinfinity was 106% (100% - 112%). Complete safety results will be presented. Conclusion: The 90% confidence intervals of the ratio for Cmax and AUC parameters were within the 80-125% predefined interval for bioequivalence based on FDA guidelines. As such, pharmacokinetic equivalence was observed between ANX-530 and Vinorelbine solution.
