Bulletin du cancer
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The epothilones are a new class of non-taxane tubulin polymerization agents obtained by natural fermentation of the myxobacteria Sorangium cellulosum. The cytotoxic activities of the epothilones, like those of the taxanes, have been linked to stabilization of microtubules, but they also have important differences. ⋯ Ixabepilone was evaluated in vivo in a panel of human and rodent tumour models, the majority of which were chosen because of their known, well-characterized resistance to paclitaxel, and seems able to overcome the over-expression of multidrug resistance and to be unaffected by mutations in the beta tubulin gene. The interest of ixabepilone was clinically confirmed in clinical studies of phase II which demonstrated a strong activity at the patients with metastatic breast cancer resistant to taxanes and in patients suffering of other types of chemoresistant tumors.
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Review Meta Analysis
[Systematic review 2007: Primary treatments of testicular germ cell tumors after radical orchydectomy].
The "Standards, Options and Recommendations" (SOR)program in oncology, has been initiated in 1993 by the Federation of French Cancer Centres and is realised in collaboration with public and private clinicians,professional federations, scientific societies and since 2005 with National cancer institute. Its aims are to develop clinical practice guidelines (CPG), health technologic assessment reports and systematic reviews. By preparing the latter, it provides support to the scientific societies for the update of their CPG. In this context, the SOR, in collaboration with the French Association of Urology (AFU), has developed a systematic review on the management of nonseminomatous (NSTGC) or seminomatous(STGC) testicular germ cell cancer treated with primary radiotherapy (RT), chemotherapy (CT) or surveillance (SV) after radical orchidectomy. Today, 80 % of patients with testicular germ cell cancer, including metastatic stage, can be cured. Actual challenges are to limit morbidity and late sequels of treatments while maintaining their therapeutic efficacy. Following this goal, surveillance, considered as a therapeutic option, is being broadly developed particularly for localised tumours. ⋯ The choice of risk-adapted treatment for patients with locally NSTGC of the testis seems to be appropriate: SV for low risk patients and CT for others. For advanced stage, the suppression of bleomycine remains questionable. For local STGC, the choice of SV or CT versus RT needs to be confirmed by RCT with prolonged follow-up according to promising results in term of toxicity obtained with carboplatine or lower irradiation dose (20 Gy instead of 30 Gy). Finally, for advanced STGC, the utility of carboplatine single agent treatment versus cisplatin-based combination chemotherapy has not been proved.
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The development of molecular targeted therapies requires some specific methodological approaches. Dose-limiting toxicities are rare in phase I studies the maximal tolerated dose is rarely established. ⋯ All of them are indicated in specific situations. The discontinuation treatment studies and the validation of biomarkers (as surrogate endpoints or as classifiers) are the two main particularities of phase III studies designed for the assessment of molecular targeted therapies.