Dose-dense adjuvant chemotherapy in node-positive breast cancer: docetaxel followed by epirubicin/cyclophosphamide (T/EC), or the reverse sequence (EC/T), every 2 weeks, versus docetaxel, epirubicin and cyclophosphamide (TEC) every 3 weeks. AERO B03 randomized phase II study.

BACKGROUND: Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive patients but optimal dose and schedule remain undetermined. This study aimed to select a dose-dense regimen for further assessment in phase III studies. PATIENTS AND METHODS: Ninety-nine patients with node-positive invasive breast adenocarcinoma were randomly assigned to docetaxel (Taxotere) (T) 75 mg/m2, epirubicin (E) 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 (TEC)x6, every 3 weeks; E 100 mg/m2, C 600 mg/m2 x 4, then T 100 mg/m2 x 4 (EC-->T) or the reverse sequence (T-->EC), every 2 weeks, with pegfilgrastim support. The primary end point was the incidence of grade 4 toxicity. RESULTS: Dose intensity was almost doubled with dose-dense regimens, compared with TEC. Twenty-seven patients experienced grade 4 toxicity: 26%, 40% and 18% with TEC, EC-->T and T-->EC, respectively, mainly neutropenia, but febrile neutropenia occurred only in 11%, 10% and 3%. Grade 3-4 nail disorders, hand-foot syndrome and peripheral neuropathy occurred in 46%, 73% and 68% of patients with TEC, EC-->T and T-->EC, respectively. CONCLUSIONS: Dose-dense regimens yield more frequent and severe nonhematological toxic effects than standard dose TEC regimen. Though grade 4 toxicity rates appear acceptable with the T-->EC regimen, the incidence of grade 3-4 events makes it difficult to recommend either dose-dense regimen for further investigation.

[Fatal acute encephalopathy due to 5-fluorouracil treatment]. / Encéphalopathie aiguë fatale secondaire à un traitement par 5-fluoro-uracile.

INTRODUCTION: Encephalopathies from 5 fluorouracil (5FU) are rare and generally resolve favorably. CASE: Six days after her first course of chemotherapy combining 5FU and cisplatin, a 45-year-old woman developed acute encephalopathy with altered consciousness and convulsions. MRI showed hyperintense signals of the white matter, mainly ventricular. Despite symptomatic treatment and thiamine perfusion in intensive care, the patient deteriorated and resuscitation failed. Blood tests confirmed 5FU toxicity. DISCUSSION: 5FU encephalopathies are rare and most often resolve favorably after treatment is stopped. Two pathophysiologic mechanisms may explain these encephalopathies: a deficit of dihydropyridine dehydrogenase, leading to an increased level of serum uracil with digestive and mucosal toxicity, or interaction of 5FU catabolites with various intracerebral metabolic pathways.

[Hormone therapy and breast cancer: a review]. / Hormonothérapies et cancers du sein: mise au point.

PURPOSE: Tamoxifen as adjuvant hormonal therapy after hormonosensitive-breast cancer surgery is well established nowadays, as well as its efficacy in first-line therapy of advanced hormonosensitive breast cancers. Research of drugs which could be effective, with little toxicity, and having a positive impact on cardiovascular disease or bone is an important issue. CURRENT KNOWLEDGE AND KEY POINTS: New drugs are in development or will soon be on the market to permit second or third lines of treatment with respect to effectiveness and quality of life, such as new anti-estrogens or selective estrogen receptors modulators or aromatase inhibitors. Their principal characteristics are reviewed through recent data. FUTURE PROSPECTS AND PROJECTS: Prevention of breast cancer is a pertinent question and major publications are presented. Finally, the controversy about the possible reintroduction of replacement hormonal therapy after breast cancer will be questioned through trials.

[Patients' rights during medical research and specifics in oncology (in France)]. / Droit des personnes dans les études de recherche clinique et particularités de l'oncologie (en France).

PURPOSE: Clinical research in oncology is part of the care, instead of being theoretical, because it can offer new drugs to patients who are suffering from severe illnesses, but also because it offers better practices. The vulnerability of patients suffering from cancers, at each stage of the disease, requires special protection. Because of its multiple aspects, clinical research in oncology asks ethical questions. Medical deontology and laws, national and supranational, allow research with respect to the subject. The present article reviews these texts. CURRENT KNOWLEDGE AND KEY POINTS: The rights of the person involved in clinical trials essentially consist of information and consent, but also the right to refuse, and the confidentiality of data collected. More subtle rights are now emerging because of new technologies, such as genetics. One of them is the right to be protected as a member of the human race, which is in continuity with human rights. FUTURE AND PROJECTS: Finally, medical responsibility during research is increasing. It responds to the right of each person to see that his dignity is respected, although this dignity may be difficult to define. One of the more pertinent questions in building 'evidence-based ethics' concerns research into the evaluation by the persons themselves involved in the research.