6 results on '"Puozzo, C."'
Search Results
2. 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]
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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)
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- 2009
3. 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
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- 2008
4. Influence on Busilvex® pharmacokinetics of clonazepam compared to previous phenytoin historical data
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Carreras, E., Cahn, J. Y., Puozzo, C., Kröger, N., GUILLERMO SANZ, Buzyn, A., Bacigalupo, A., Vernant, J. P., TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut de Recherche Pierre Fabre, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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Male ,Transplantation Conditioning ,MESH: Busulfan ,MESH: Drug Interactions ,MESH : Transplantation Conditioning ,MESH : Prospective Studies ,MESH : Alkylating Agents ,Clonazepam ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,MESH: Clonazepam ,Drug Interactions ,MESH : Female ,Prospective Studies ,MESH : Busulfan ,MESH : Immunosuppressive Agents ,MESH : Cyclophosphamide ,MESH: Transplantation Conditioning ,MESH : Seizures ,MESH: Middle Aged ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,MESH : Adult ,MESH: Seizures ,MESH: Alkylating Agents ,MESH: Young Adult ,Hematologic Neoplasms ,Anticonvulsants ,Female ,MESH: Immunosuppressive Agents ,MESH : Hematologic Neoplasms ,Immunosuppressive Agents ,Adult ,MESH : Anticonvulsants ,Alkylating Agents ,Adolescent ,MESH : Male ,MESH : Young Adult ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Young Adult ,MESH: Anticonvulsants ,Seizures ,MESH : Adolescent ,MESH : Hematopoietic Stem Cell Transplantation ,Humans ,MESH : Middle Aged ,Busulfan ,Cyclophosphamide ,MESH: Hematopoietic Stem Cell Transplantation ,MESH: Adolescent ,MESH: Humans ,MESH : Humans ,MESH: Cyclophosphamide ,MESH: Adult ,MESH: Male ,MESH: Prospective Studies ,MESH : Clonazepam ,MESH : Drug Interactions ,MESH: Phenytoin ,Phenytoin ,MESH: Female ,MESH : Phenytoin ,MESH: Hematologic Neoplasms - Abstract
International audience; 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.
5. Oral vinorelbine in the treatment of non-small cell lung cancer: rationale and implications for patient management
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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
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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.
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- 2007
6. Oral versus intravenous vinorelbine: clinical safety profile
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Christian Puozzo, Vittorio Gebbia, GEBBIA V, and PUOZZO C
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Adult ,Nausea ,Administration, Oral ,Biological Availability ,Pharmacology ,Vinblastine ,Vinorelbine ,Absorption ,Eating ,Therapeutic index ,Cytochrome P-450 Enzyme System ,Pharmacokinetics ,Oral administration ,Neoplasms ,medicine ,Humans ,Pharmacology (medical) ,Infusions, Intravenous ,Aged ,breast cancer, non-small cell lung cancer (NSCLC), oral vinorelbine ,business.industry ,Standard treatment ,Age Factors ,General Medicine ,Middle Aged ,Antineoplastic Agents, Phytogenic ,Liver ,Vomiting ,medicine.symptom ,business ,Drug metabolism ,Half-Life ,medicine.drug - Abstract
The availability of chemotherapeutic drugs administrable by oral route represents a step forward in the management of cancer patients. Among oral agents, vinorelbine is particularly interesting for its pharmacological characteristics and clinical efficacy. Oral vinorelbine is rapidly absorbed (1.5-3 hours) with an elimination half-life of approximately 40 hours. It shows a low level of binding to plasma proteins (13%), is highly bound to platelets (78%) and has a hepatic metabolism and an absolute bioavailability of 40% with a moderate and similar interpatient variability for the two forms. Food has no influence on the pharmacokinetic profile of oral vinorelbine even if nausea/vomiting is less frequent and less severe in the fed patients than in the fasting patients. Therefore, to ensure patient comfort, it is recommended that oral vinorelbine is administered with a snack. All the metabolites of oral vinorelbine have been identified and, among these, only deacetyl-vinorelbine presented activity demonstrating that for both oral and intravenous (i.v.) routes of administration the drug has the same metabolism pattern. Oral vinorelbine is eliminated mainly in a unconjugated form via the bile. In this process, the CYP 3A4 isoform of cytochrome P450 is mostly involved. Absorption of oral vinorelbine is not delayed in elderly patients. After oral administration, blood concentrations of vinorelbine in elderly patients are within the range of values observed in younger patients. The absolute bioavailability is close to 38% in elderly whereas it is close to 40% in younger patients. This difference is not significant. As compared to the intravenous drug, oral vinorelbine demonstrated linear pharmacokinetics as well an absolute bioavailability of approximately 40%, and a reliable dose-correspondence of 80 mg/m2 oral form --> 30 mg/m2 i.v. and 60 mg/m2 oral --> 25 mg/m2 i.v. Therefore, i.v. and oral forms show similar interindividual variability, same metabolism pattern, reproducible intra-patient blood exposure, and same pharmacokinetic-pharmacodynamic relationship. Oral vinorelbine has shown significant activity in advanced non-small cell lung cancer. Given at 60 mg/m2/week for the first 3 administrations and then increased to 80 mg/m2/week achieved the same efficacy as i.v. vinorelbine in terms of progression-free survival, overall survival, objective response. Mild-to-moderate gastrointestinal toxicity, easily manageable with standard treatment was recorded. Reproducible efficacy compared to previously reported results with vinorelbine i.v. Also, in advanced breast cancer, oral vinorelbine has shown significant activity with a good therapeutic index. Albeit no formal comparison between the oral and the intravenous formulations of vinorelbine has been made, however, the oral route seems to offer major advantages to patients who are faced with a clear decrease in the frequency of hospital admissions as compared to that needed to give intravenous chemotherapy.
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- 2005
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