Bulletin du cancer
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Trastuzumab (Herceptin), a recombinant, humanised, monoclonal-antibody that targets human epidermal growth factor receptor 2 (HER2), has been approved as an adjuvant therapy for HER2-positive early breast cancer. The aim of this study was to assess the incremental cost-effectiveness ratio of this treatment compared with adjuvant therapy alone in the French setting. A cost-effectiveness analysis was performed using a Markov state transition model. ⋯ For 1 000 patients with a 10-year follow-up, an adjuvant therapy with trastuzumab would avoid 49.7 loco-regional recurrences, 179.5 distant recurrences and 133.4 deaths. The incremental discounted cost of trastuzumab therapy over a lifetime horizon was estimated at 27594 euro per patient in association with a discounted gain of 2.27 life-years. In accordance with the techniques of economical evaluation, the utilization of trastuzumab as an adjuvant therapy in patients with early HER2 positive breast cancer improves patient survival with an acceptable cost-effectiveness ratio in the French setting (incremental cost-effectiveness ratio of 12,148 euros /LYG).
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Dosing of anticancer drugs in adults is mostly adjusted to estimated body surface area or body weight. Dose normalisation to body size is assumed to decrease the interindividual pharmacokinetic and pharmacodynamic variability. This approach is rarely validated before approval. ⋯ Moreover, the abandon of body surface area in dosing of new drugs in phase I trials has been recommended. At the present time, body size continues to be used in the dosing of new agents in adult patients. This review presents the concepts and the limits of weight and body surface area-based dosing of anticancer drugs in adult patients.
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The detection of overexpression of human epidermal growth factor receptor 2 (HER2) in some breast cancer tumors has led to the development of a targeted treatment that is tumor selective, effective at extending life expectancy in the patients with advanced or early breast cancers. Trastuzumab (Herceptin), a humanized monoclonal antibody to HER2 is indicated for patients whose tumor demonstrates an amplified copy number for the HER2 oncogene and/or overexpresses the HER2 oncoprotein. Despite a high level of efficacy in combination with chemotherapy, trastuzumab as single agent has limited effectiveness (up to 30% response rates) and patients who respond to trastuzumab will relapse despite continued treatment. ⋯ Thus, the co-expression of growth factor receptors (EGFR family, IGF-1 R), and the activation of PI3K-Akt pathway, mainly by loss of PTEN function may be responsible for the resistance phenotype. It would be interesting to identify the mechanisms of trastuzumab resistance in breast tumors in order to reverse or prevent it. The characterization of these mechanisms would also provide novel strategies for alternative treatments.
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Review Practice Guideline
[Postmastectomy pain syndrome evidence based guidelines and decision trees].
A multidisciplinary expert group had reviewed all scientific data available of post mastectomy pain syndrome. Seventy six publications were retained and thirty evidence based diagnosis, treatment and follow-up recommendations are listed. ⋯ Evaluation and closer follow-up are necessary. Several decisional trees are proposed.