Dorothée R Sémiond

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PURPOSE To assess the feasibility of administering XRP6258, a new taxane with a low affinity for the multidrug resistance 1 protein, as a 1-hour i.v. infusion every 3 weeks. The study also sought to determine the maximum tolerated dose and the recommended dose, to describe the pharmacokinetic (PK) behavior of the compound, and to seek preliminary evidence(More)
BACKGROUND Although the taxanes paclitaxel and docetaxel are among the most active agents for the treatment of a wide range of cancers, tumours often develop resistance to these treatments. Cabazitaxel is a novel taxane active in both preclinical models of chemotherapy-sensitive and -resistant human tumours and patients with advanced prostate cancer that(More)
To develop a population pharmacokinetic (PK) model for cabazitaxel in patients with advanced solid tumors and examine the influence of demographic and baseline parameters. One hundred and seventy patients who received cabazitaxel (10–30 mg/m2, 1-h IV infusion) every 7 or 21 days in five Phase I–III studies were analyzed by non-linear mixed-effect modeling(More)
1. TXD258, a new taxoid antitumor agent, is a poor substrate for the P-glycoprotein (P-gp) in Caco-2 cells. In this study, we investigated the amount of drug accumulating in the brains of rats and mice under a variety of conditions (dose and infusion time, species and plasma concentration) using conventional in vivo pharmacokinetic techniques and in situ(More)
PURPOSE Taxanes are important chemotherapeutic agents with proven efficacy in human cancers, but their use is limited by resistance development. We report here the preclinical characteristics of cabazitaxel (XRP6258), a semisynthetic taxane developed to overcome taxane resistance. EXPERIMENTAL DESIGN Cabazitaxel effects on purified tubulin and on(More)
Cabazitaxel is a semisynthetic taxane approved for the treatment of patients with hormone-refractory metastatic prostate cancer (now known as metastatic castration-resistant prostate cancer) treated previously with a docetaxel-containing treatment regimen. The human plasma pharmacokinetics of cabazitaxel have been described previously, but detailed analyses(More)
PURPOSE To define the maximum tolerated dose (MTD), the recommended phase II dose, the optimal infusion duration and pharmacokinetics of the semisynthetic taxoid derivative RPR 109881A, given as a 1-h or 3-h infusion every 3 weeks. PATIENTS AND METHODS RPR109881A was administered as a 1-h i.v. infusion to 34 patients (study 1) with oral steroids as(More)
PURPOSE To assess the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary antitumor activity of oral irinotecan given in combination with capecitabine to patients with advanced, refractory solid tumors. PATIENTS AND METHODS Patients were treated from day 1 with irinotecan capsules given once daily for 5 consecutive days (50(More)
While first-generation taxanes are valuable treatment options for many solid tumors, they are limited by an inability to cross the blood–brain barrier (BBB) and by limited efficacy in pediatric patients. Following promising preclinical data for the next-generation taxane cabazitaxel, including activity in tumor models fully sensitive, poorly sensitive or(More)
BACKGROUND Most patients with metastatic breast cancer (MBC) progress after chemotherapy. Cabazitaxel (XRP6258) is a new taxoid that is active in chemotherapy-resistant tumour cell lines. The objectives of this phase I/II study were to assess the maximum tolerated dose (MTD), safety profile, pharmacokinetics, and activity of cabazitaxel plus capecitabine in(More)