11 results on '"Puozzo, C."'
Search Results
2. Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors
- Author
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Marty, M., Fumoleau, P., Adenis, A., Rousseau, Y., Merrouche, Y., Robinet, G., Senac, I., and Puozzo, C.
- Published
- 2001
3. Influence on Busilvex (R) Pharmacokinetics of Clonazepam Compared to Previous Phenytoin Historical Data
- Author
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Carreras, E., Cahn, J. Y., Puozzo, C., Kroeger, N., Sanz, G., Buzyn, A., Bacigalupo, A., and Vernant, J. P.
- Published
- 2010
4. Dose-ranging study of metronomic oral vinorelbine in patients with advanced refractory cancer
- Author
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Briassoulis, E. Ch, Pappas, P., Puozzo, C., Ch, F. Tolis, Fountzilas, George, Dafni, U., Marselos, M., Pavlidis, Nicholas, and Pavlidis, Nicholas [0000-0002-2195-9961]
- Subjects
Male ,Cancer Research ,Peripheral neuropathy ,Blood sampling ,Administration, Oral ,Pharmacology ,Interleukin 8 ,Treatment response ,Gastroenterology ,Steady state ,Feasibility studies ,chemistry.chemical_compound ,Oral administration ,Phytogenic ,Neoplasms ,Antineoplastic agents ,Regulator protein ,80 and over ,Antineoplastic Agents, Phytogenic/*administration & dosage/adverse effects ,Disease course ,Middle aged ,Drug safety ,Priority journal ,Aged, 80 and over ,Vinblastine/administration & dosage/adverse effects/*analogs & ,Nausea ,Kidney cancer ,Vinorelbine ,Middle Aged ,Dose-ranging study ,Vascular endothelial growth factor ,Epistaxis ,Oncology ,Toxicity ,Administration ,Hypertension ,Female ,Sarcoma ,Cohort analysis ,medicine.drug ,Human ,Diarrhea ,Oral ,Adult ,medicine.medical_specialty ,Vomiting ,Navelbine ,Major clinical study ,derivatives/pharmacokinetics ,Vinblastine ,Article ,Treatment duration ,Drug Administration Schedule ,Pharmacokinetics ,Internal medicine ,Advanced cancer ,medicine ,Humans ,Antineoplastic activity ,Aged ,Basic fibroblast growth factor ,Thyroid medullary carcinoma ,Vasculotropin ,Drug dose escalation ,business.industry ,Drug administration schedule ,Cancer ,Kaposi sarcoma ,Drug evaluation ,Leukopenia ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Neoplasms/*drug therapy ,Drug efficacy ,Biological marker ,chemistry ,Drug metabolite ,Drug Evaluation ,Feasibility Studies ,Angiogenesis ,business ,Controlled study - Abstract
Aim: To determine the safe dose range and pharmacokinetics of metronomic oral vinorelbine and obtain preliminary data on biomarkers and efficacy in patients with advanced cancer. Methods: Successive cohorts of patients received escalated doses of oral vinorelbine given thrice a week until disease progression, unacceptable toxicity (UT), or consent withdrawal. UT was any grade 4 toxicity, or grade 2 or 3 toxicity that would result to longer than 2-week break during the first 2 months of treatment. Blood samples were collected for pharmacokinetics and quantification of angiogenesis regulatory proteins. Results: Sixty-two patients (median age, 60 years) enrolled at six dose levels from 20 to 70 mg and received treatment for median 12.25 weeks (range, 2-216+). Unacceptable toxicity occurred in two of six patients treated at 60 mg (leucopenia grade 4 and epistaxis grade 2) and in one at 70 mg (leucopenia grade 2). The upper metronomic dose was 50 mg. Objective antitumor response documented in eight cases and 32% of patients experienced disease stability for minimum 6 months. Three responders (renal cancer, medullary thyroid carcinoma, and Kaposi sarcoma) received nonstop treatment for over 3 years without overt toxicity. Low pretreatment levels of circulating interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor were found predictors of efficacy. Steady-state concentrations of vinorelbine and its active metabolite ranged from 0.5 to 1.5 ng/mL. Conclusions: Metronomic administration of oral vinorelbine is feasible at doses up to 50 mg thrice a week and can yield sustainable antitumor activity without overt toxicity, probably through antiangiogenic mechanism. Further clinical investigation is warranted. (Clin Cancer Res 2009;15(20):6454–61)
- Published
- 2009
5. Metronomic Oral Vinorelbine in Patients with Recurrent Breast, Prostate or Non-Small Cell Lung Cancer: Optimal Dose-Finding Trial of the Hellenic Cooperative Oncology Group
- Author
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Briasoulis, E., Kalofonos, H., Samantas, E., Varthalitis, I., Syrigos, K. N., Fountzilas, G., Pappas, P., Sainis, I., Puozzo, C., and Pavlidis, N.
- Abstract
Annals of Oncology
- Published
- 2008
6. Oral vinorelbine in the treatment of non-small cell lung cancer: rationale and implications for patient management
- Author
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Christian Puozzo, Vittorio Gebbia, Mary O'Brien, Rudolf M. Huber, Richard J. Gralla, Ulrich Gatzemeier, GRALLA RJ, GATZEMEIER U, GEBBIA V, HUBER R, O'BRIEN M, and PUOZZO C
- Subjects
medicine.medical_specialty ,Lung Neoplasms ,medicine.drug_class ,Administration, Oral ,Pharmacology ,Vinorelbine ,Vinblastine ,Route of administration ,chemistry.chemical_compound ,Oral administration ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Antiemetic ,Humans ,Pharmacology (medical) ,Randomized Controlled Trials as Topic ,business.industry ,Combination chemotherapy ,Antineoplastic Agents, Phytogenic ,Combined Modality Therapy ,Gemcitabine ,Carboplatin ,Bioavailability ,Surgery ,chemistry ,Oral vinorelbine, small cell lung cancer ,business ,medicine.drug - Abstract
Vinorelbine is an established treatment for advanced non-small cell lung cancer (NSCLC), both as a single agent and in combination chemotherapy. Recently, an oral form of this agent has been developed. Before accepting an established agent in a different administration form, rigorous testing is required to answer such questions as reliable bioavailability, continued safety and preservation of efficacy. In addition, an oral agent must provide patient convenience and acceptance, while being an economically sound approach. Oral vinorelbine was found to have acceptable and reliable pharmacokinetic profiles at clinically relevant dosage levels. Oral vinorelbine was found to have approximately 40% bioavailability; thus, a dose of 80 mg/m(2) orally is the equivalent of 30 mg/m(2) intravenously, and 60 mg/m(2) orally is the equivalent of 25 mg/m(2) intravenously. Studies also concluded a lack of food effect on the administration of oral vinorelbine. In addition, no drug-drug interactions were found with a variety of commonly used antineoplastic agents.Vinorelbine, either orally or intravenously, has been investigated in randomised phase II trials as a single agent and in combination with cisplatin or carboplatin in patients with NSCLC. In general, response and survival results with oral vinorelbine appeared similar to the intravenous agent. Adverse-effect profiles were also similar for the two formulations. Clearly, the issue of venous irritation does not exist with oral vinorelbine; however, nausea and vomiting were more frequent when vinorelbine was administered orally compared with intravenously when no planned antiemetic therapy is given.
- Published
- 2007
7. Influence on Busilvex pharmacokinetics of clonazepam compared to previous phenytoin historical data.
- Author
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Carreras E, Cahn JY, Puozzo C, Kröger N, Sanz G, Buzyn A, Bacigalupo A, and Vernant JP
- Subjects
- Adolescent, Adult, Alkylating Agents administration & dosage, Alkylating Agents pharmacokinetics, Busulfan administration & dosage, Busulfan adverse effects, Busulfan blood, Clonazepam administration & dosage, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Drug Interactions, Female, Hematologic Neoplasms metabolism, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation methods, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents pharmacokinetics, Male, Middle Aged, Prospective Studies, Seizures prevention & control, Transplantation Conditioning methods, Young Adult, Anticonvulsants pharmacokinetics, Busulfan pharmacokinetics, Clonazepam pharmacokinetics, Phenytoin pharmacokinetics
- Abstract
This study investigated the effect of seizure prophylaxis on busulfan (Bu) plasma exposure. Twenty-four adult patients received an intravenous Bu-cyclophoshamide conditioning regimen prior to bone marrow transplantation. Busilvex (0.8 mg/kg) was administered every six hours during four consecutive days. Clonazepam (0.025 to 0.03 mg/kg/day as a continuous 12-h i.v. infusion) was administered at least 12 hours prior to i.v. Bu dosing and continued until 24 hours after the last dose. Pharmacokinetic (PK) data were compared with those previously collected in patients (n=127) treated with phenytoin for seizure prophylaxis. Through population PK analysis, a 10% average increase (coefficient of variation, RSE=5.35%) in total clearance of Bu was quantified when Bu was associated with clonazepam as compared to phenytoin, which was considered as not being clinically relevant. The suspected induction on Bu metabolism by phenytoin should have resulted in the opposite effect. The patient efficacy and safety profiles were comparable between the two cohorts.
- Published
- 2010
8. Novel pharmacokinetic behavior of intravenous busulfan in children with thalassemia undergoing hematopoietic stem cell transplantation: a prospective evaluation of pharmacokinetic and pharmacodynamic profile with therapeutic drug monitoring.
- Author
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Gaziev J, Nguyen L, Puozzo C, Mozzi AF, Casella M, Perrone Donnorso M, Gravina P, Sodani P, Marziali M, Isgrò A, Simone MD, Andreani M, Formosa A, Testi M, Federici G, Bernardini S, and Lucarelli G
- Subjects
- Adolescent, Adult, Base Sequence, Busulfan pharmacology, Child, Child, Preschool, DNA Primers genetics, Disease-Free Survival, Drug Monitoring, Female, Genotype, Glutathione Transferase genetics, Graft Survival, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents pharmacokinetics, Immunosuppressive Agents pharmacology, Infant, Injections, Intravenous, Male, Metabolic Clearance Rate, Prospective Studies, Thalassemia drug therapy, Treatment Outcome, Young Adult, Busulfan administration & dosage, Busulfan pharmacokinetics, Hematopoietic Stem Cell Transplantation, Thalassemia metabolism, Thalassemia therapy
- Abstract
We prospectively studied the pharmacokinetics (PK) and clinical outcomes of intravenous busulfan (Bu) in 71 children with preexisting liver damage who underwent hematopoietic stem cell transplantation for thalassemia. Intravenous Bu was administered every 6 hours as part of a conditioning regimen with PK-based dose adjustment to target a conservative area under the concentration-versus-time curve (AUC) range (900-1350 microMol*min). The first-dose Bu clearance (CL) was significantly higher than the subsequent daily CL that remained unchanged in the ensuing days. One-third of patients required dose escalation based on dose 1 AUC, whereas dose reduction was needed in the subsequent days. At doses 5, 9, and 13, 78%, 81%, and 87% of patients, respectively, achieved the target range of AUC. A population PK analysis confirmed that the first-dose CL was 20% higher and that body weight was the most important covariate to explain PK variability. Patients with variant GSTA1*B had a 10% lower Bu CL than wild-type. These results suggest that the disease-specific behavior of intravenous Bu PK should be considered for PK-guided dose adjustment in patients with thalassemia, and the use of a conservative AUC range resulted in low toxicity, good engraftment, and good survival rate.
- Published
- 2010
- Full Text
- View/download PDF
9. Dose-ranging study of metronomic oral vinorelbine in patients with advanced refractory cancer.
- Author
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Briasoulis E, Pappas P, Puozzo C, Tolis C, Fountzilas G, Dafni U, Marselos M, and Pavlidis N
- Subjects
- Administration, Oral, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Phytogenic adverse effects, Drug Administration Schedule, Drug Evaluation, Feasibility Studies, Female, Humans, Male, Middle Aged, Vinblastine administration & dosage, Vinblastine adverse effects, Vinblastine pharmacokinetics, Vinorelbine, Antineoplastic Agents, Phytogenic administration & dosage, Neoplasms drug therapy, Vinblastine analogs & derivatives
- Abstract
Aim: To determine the safe dose range and pharmacokinetics of metronomic oral vinorelbine and obtain preliminary data on biomarkers and efficacy in patients with advanced cancer., Methods: Successive cohorts of patients received escalated doses of oral vinorelbine given thrice a week until disease progression, unacceptable toxicity (UT), or consent withdrawal. UT was any grade 4 toxicity, or grade 2 or 3 toxicity that would result to longer than 2-week break during the first 2 months of treatment. Blood samples were collected for pharmacokinetics and quantification of angiogenesis regulatory proteins., Results: Sixty-two patients (median age, 60 years) enrolled at six dose levels from 20 to 70 mg and received treatment for median 12.25 weeks (range, 2-216+). Unacceptable toxicity occurred in two of six patients treated at 60 mg (leucopenia grade 4 and epistaxis grade 2) and in one at 70 mg (leucopenia grade 2). The upper metronomic dose was 50 mg. Objective antitumor response documented in eight cases and 32% of patients experienced disease stability for minimum 6 months. Three responders (renal cancer, medullary thyroid carcinoma, and Kaposi sarcoma) received nonstop treatment for over 3 years without overt toxicity. Low pretreatment levels of circulating interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor were found predictors of efficacy. Steady-state concentrations of vinorelbine and its active metabolite ranged from 0.5 to 1.5 ng/mL., Conclusions: Metronomic administration of oral vinorelbine is feasible at doses up to 50 mg thrice a week and can yield sustainable antitumor activity without overt toxicity, probably through antiangiogenic mechanism. Further clinical investigation is warranted.
- Published
- 2009
- Full Text
- View/download PDF
10. Combination chemotherapy of vinorelbine and cisplatin: a phase I pharmacokinetic study in patients with metastatic solid tumors.
- Author
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Delord JP, Puozzo C, Lefresne F, and Bugat R
- Subjects
- Administration, Oral, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols blood, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cisplatin administration & dosage, Cisplatin adverse effects, Cisplatin blood, Cisplatin pharmacokinetics, Drug Interactions, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Neoplasms blood, Neoplasms drug therapy, Vinblastine administration & dosage, Vinblastine adverse effects, Vinblastine analogs & derivatives, Vinblastine blood, Vinblastine pharmacokinetics, Vinorelbine, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Neoplasms metabolism
- Abstract
Background: Vinorelbine (VRL)-cisplatin (CDDP) is an active doublet for advanced non-small cell lung cancer. CDDP has a narrow therapeutic index and may produce a cumulative nephrotoxicity over the treatment period. This study was to assess the risks of drug-drug interaction (DDI) over 3 consecutive cycles of VRL-CDDP combined treatments., Patients and Methods: An open-label, nonrandomised, phase I study was carried out. Patients with normal hepatic/renal functions. D1: CDDP 100 mg/m2--D1, D8: oral VRL 60 mg/m2 q3w. Pharmacokinetics (PK) over the first 3 cycles. PK comparison between cycles and between study vs. literature., Results: Thirteen patients were evaluable for safety and PK. Adverse events were those frequently observed with CDDP or VRL, and consisted of hematological toxicities, nausea, vomiting and constipation. Concerning VRL and CDDP PK, no difference was detected between the 3 administrations nor between the study and reference values., Conclusion: The absence of DDI between CDDP and oral VRL was demonstrated over 3 consecutive cycles of therapy.
- Published
- 2009
11. Population pharmacokinetics model and limited sampling strategy for intravenous vinorelbine derived from phase I clinical trials.
- Author
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Nguyen L, Tranchand B, Puozzo C, and Variol P
- Subjects
- Adult, Aged, Antineoplastic Agents, Phytogenic blood, Bayes Theorem, Clinical Trials, Phase I as Topic, Female, Humans, Injections, Intravenous, Male, Middle Aged, Models, Biological, Retrospective Studies, Sampling Studies, Vinblastine blood, Vinorelbine, Antineoplastic Agents, Phytogenic pharmacokinetics, Vinblastine analogs & derivatives, Vinblastine pharmacokinetics
- Abstract
Aims: a) To characterize the pharmacokinetics of intravenous vinorelbine, b) to use a population analysis for the identification of patient covariates that might appreciably influence its disposition and c) to define a limited sampling strategy for further Bayesian estimation of individual pharmacokinetic parameters., Methods: All data were collected from 64 patients (99 courses) entered in three different phase I trials that have been previously reported. All patients received vinorelbine as a 20 min infusion with dose levels ranging from 20-45 mg m-2. The population pharmacokinetic model was built in a sequential manner on a subset of two-thirds of the data, starting with a covariate-free model then progressing to a covariate model using the nonlinear-mixed effect methodology. The remaining one-third of the data were used to validate several sparse sampling designs., Results: A linear three-compartment model characterized vinorelbine blood concentrations (n=1228). Two primary pharmacokinetic parameters (total clearance and volume of distribution) were related to various combinations of covariates. The relationship for total clearance (CLtotal (l h-1)=29.2xBSAx(1-0.0090 Plt)+6.7xWt/Crs) was dependent on the patient's body surface area (BSA), weight (Wt), serum creatinine (Crs) and platelet count before administration (Plt). The optimal limited sampling strategy consisted of a combination of three measured blood concentrations; the first immediately before the end of infusion or 20 min later, the second at either 1 h, 3 h or 6 h and the third at 24 h after drug administration., Conclusions: A population pharmacokinetic model and a limited sampling strategy for intravenous vinorelbine have been developed. This is the first population analysis performed on the basis of a large phase I database that has identified clinical covariates influencing the disposition of i.v. vinorelbine. The model can be used to obtain accurate Bayesian estimates of pharmacokinetic parameters in situations where extensive pharmacokinetic sampling is not feasable.
- Published
- 2002
- Full Text
- View/download PDF
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