Randomized, double-blind trial of F14512, a polyamine-vectorized anticancer drug, compared with etoposide phosphate, in dogs with naturally occurring lymphoma.

F14512 is an epipodophyllotoxin derivative from etoposide, combined with a spermine moiety introduced as a cell delivery vector. The objective of this study was to compare the safety and antitumor activity of F14512 and etoposide phosphate in dogs with spontaneous non-Hodgkin lymphoma (NHL) and to investigate the potential benefit of F14512 in P-glycoprotein (Pgp) overexpressing lymphomas. Forty-eight client-owned dogs with intermediate to high-grade NHL were enrolled into a randomized, double-blind trial of F14512 etoposide phosphate.

A randomised, multicentre open-label phase II study to evaluate the efficacy, tolerability and pharmacokinetics of oral vinorelbine plus cisplatin versus intravenous vinorelbine plus cisplatin in Chinese patients with chemotherapy-naive unresectable or metastatic non-small cell lung cancer.

Background: A phase II study to evaluate the efficacy, tolerability and pharmacokinetics of oral or intravenous vinorelbine (VRL) plus cisplatin (CDDP) in Chinese patients with non-small cell lung cancer (NSCLC).

Methods: One hundred and thirty-one patients were randomised to oral VRL 60 mg/m (arm A) or intravenous VRL 25 mg/m (arm B) on days 1 and 8, plus CDDP 80 mg/m on day 1 (both arms). VRL was increased to 80 mg/m (arm A) or 30 mg/m (arm B) in cycles 2-4 in the absence of toxicity.

Effect of ethnicity on vinorelbine pharmacokinetics: a population pharmacokinetics analysis.

Background: Pharmacokinetics of vinorelbine is mainly known from studies conducted in European patients. Interethnic differences in drug disposition may, however, induce interethnic variation in drug exposure. This paper aimed to evaluate the effect of ethnicity on the bioavailability and clearance of oral and intravenous vinorelbine.

Phase I dose-escalation study of F14512, a polyamine-vectorized topoisomerase II inhibitor, in patients with platinum-refractory or resistant ovarian cancer.

Purpose To determine the maximum tolerated dose (MTD) of F14512, a topoisomerase II inhibitor designed to target cancer cells through the polyamine transport system, (three-hour daily infusion given for 3 consecutive days every 3 weeks) in platinum-refractory or resistant ovarian cancer. Other objectives were safety, pharmacokinetics (PK), PK/pharmacodynamics relationship, and efficacy. Methods This was an open-label, dose-escalation, multicenter phase I study.

Better characterization of vinflunine pharmacokinetics variability and exposure/toxicity relationship to improve its use: Analyses from 18 trials.

Aims: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted as yet.

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma.

Purpose: F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in a phase I/II clinical trial in patients with acute myeloid leukemia. The aim of this study was to investigate F14512 potential in a new clinical indication.

New insights into the pharmacokinetics of intravenous busulfan in children with sickle cell anemia undergoing bone marrow transplantation.

Background: Busulfan (Bu) is an integral part of conditioning regimens for patients with sickle cell anemia (SCA) undergoing transplantation. Patients with SCA might predispose to transplant-related neurological and pulmonary toxicities due to pre-existing disease-related cerebrovascular and lung injury. Bu therapy appears to be an important contributing factor in this context.

How to manage intravenous vinflunine in cancer patients with renal impairment: results of a pharmacokinetic and tolerability phase I study.

Aims: Vinflunine (VFL) ditartrate, a novel tubulin-targeted inhibitor, is registered for the treatment of patients with advanced or metastatic urothelial transitional cell carcinoma. This phase I study assessed the effect of renal impairment on the pharmacokinetics and tolerability of VFL.

Methods: VFL was infused in patients with advanced/metastatic solid tumours once every 3 weeks with anticipated dose reduction on the first cycle stratified according to the creatinine clearance (CLcr ) values.

Pharmacokinetic behavior and appraisal of intravenous busulfan dosing in infants and older children: the results of a population pharmacokinetic study from a large pediatric cohort undergoing hematopoietic stem-cell transplantation.

Background: Intravenous (IV) busulfan (Bu) dosing approved in Europe based on 5 body weight (BW) strata has been validated for targeting Bu exposures in children undergoing hematopoietic stem-cell transplantation and with mostly malignant diseases. The authors conducted an observational study aiming to investigate the behavior and ontogeny of IV Bu pharmacokinetic (PK) disposition, and to reevaluate the consistency of the BW-based dosing in very young children with rare diseases.

Methods: The observational study comprised 115 patients, mostly infants with immunodeficiencies and metabolic inherited disorders and with altered liver function and/or iron overload.

[Anticancer drug dose individualisation: from body surface area to physiology].

The doses of anticancer drugs are usually calculated according to the body surface area. This practice is based on the hypothesis that clearance is proportional to this morphologic parameter. That is rarely true, thus the pharmacodynamic effects (particularly haematological toxicity) are often better correlated with plasma drug concentrations than with doses.

Population pharmacokinetics and pharmacogenetics of imatinib in children and adults.

Purpose: The aim of this study was to explore the effect of several demographic, biological, and pharmacogenetic covariates on the disposition of imatinib and its main metabolite (CGP74588) in both adults and children.

Experimental Design: Thirty-three children with solid malignancies included in a phase II exploratory study and 34 adults with gastrointestinal stromal tumors received 340 mg/m(2) and 400 mg imatinib, respectively. Plasma imatinib and CGP74588 concentrations observed on day 1 and at steady-state were analyzed by a population pharmacokinetic method (NONMEM) to evaluate the effect of age, body weight, age, sex, albuminemia, plasma alpha1-acid glycoprotein (AGP), and eight polymorphisms corresponding to ABCB1, ABCG2, CYP3A4, CYP3A5, and AGP (pharmacogenetic data available for 46 of 67 patients).