Dose intensity and toxicity associated with Taxotere formulation: a retrospective study in a population of breast cancer patients treated with docetaxel as an adjuvant or neoadjuvant chemotherapy.

Docetaxel is an antineoplastic drug from the taxane family that inhibits tubulin polymerization. Its brand name is Taxotere. In mid-2010, the formulation of Taxotere changed from a two-vial preparation needing a predilution (T2V) to a one-vial ready-to-use preparation (T1V). The aim of this study was to compare the toxicity profile of these two formulations. This retrospective observational and monocentric study included all patients who received Taxotere-based chemotherapy (100 mg/m) as an adjuvant or a neoadjuvant treatment for localized breast cancer, following initial treatment with anthracycline-based chemotherapy. Patients received either T2V or T1V Taxotere depending on the period of treatment. The main endpoint was the ratio of the dose of Taxotere received to that scheduled (R=docetaxel dose received/docetaxel dose scheduled). The secondary endpoint was tolerance. A total of 97 patients were included: 39 in the T2V group and 58 in the T1V group. The ratio of docetaxel received/docetaxel scheduled was significantly lower in the T1V than in the T2V group (0.83 vs. 0.95, respectively; P=0.028). A higher proportion of patients did not receive the totality of the scheduled dose in the T1V than in the T2V group (28 vs. 8%, respectively; P=0.03). Furthermore, the proportion of patients experiencing cutaneous toxicity was significantly higher in the T1V than in the T2V group (50 vs. 15%, respectively; P<0.001) as well as for neurological toxicity (31 vs. 15%, respectively; P=0.03). The frequency of grade 3 toxicities was higher in the T1V than in the T2V group (50 vs. 8%, P=0.016). The frequency of idiosyncratic toxicities was not affected by the change of formulation (4.7 vs. 5.4%, P=0.98). This study shows that patients treated with the T1V formulation received a significantly smaller dose of Taxotere than patients treated with T2V. In this small retrospective study, no conclusions can be drawn as to why a change in formulation would be associated with differences in dose tolerance. However, it does encourage caution and need for clinical data analysis when adopting even minor changes in the formulation of well-known anticancer drugs.

[Paediatric specificity of antifungals use]. / Spécificités pédiatriques de l'utilisation des antifongiques.

Specificity of antifungals use in paediatric patients is linked to mycoses epidemiology in this population. Pharmacokinetics vary with patient age. Although studies are in progress, pharmacokinetic data in children are limited in number for most antifungals. Among antifungal agents, those approved in France for use in children are rare. Adverse event frequency can differ in children, as compared to frequency in adults, and drug interaction should be a major worry. Relative interest and cost of available forms in the paediatric population in not always taken into account. For each different situation, an optimal strategy of antifungals use in children should be determined.

[Interaction of viruses with cellular response to hypoxia]. / Interaction des virus avec la voie cellulaire de réponse à l'hypoxie.

Recent studies show that low oxygen tension levels in cell culture up-regulate the replication of human B19 parvovirus, Kaposi's sarcoma, and human immunodeficiency viruses as well as the expression of viral oncogenic proteins. The mechanisms of this regulation proceed with the major hypoxia-related factor, HIF-1 (hypoxia inducible factor-1). HIF-1 misregulation is implicated in the oncogenesis potential of some of these viruses.

Hypoxia enhances human B19 erythrovirus gene expression in primary erythroid cells.

Human B19 erythrovirus replicates in erythroid progenitors present in bone marrow and fetal tissues where partial oxygen tension is low. Here we show that infected human primary erythroid progenitor cells exposed to hypoxia (1% O2) in vitro increase viral capsid protein synthesis, virus replication, and virus production. Hypoxia-inducible factor-1 (HIF-1), the main transcription factor involved in the cellular response to reduced oxygenation, is shown to bind an HIF binding site (HBS) located in the distal part of the B19 promoter region, but the precise mechanism involved in the oxygen-sensitive upregulation of viral gene expression remains to be elucidated.