Bulletin du cancer
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HER2 is a member of tyrosine kinase growth factor receptor family. When activated, it induces an intracellular phosphorylation cascade leading to an increased protein transcription and cellular growth. HER2 is overexpressed or amplified in 20 to 30% of invasive breast cancer where it plays an important role in the natural history of the disease. ⋯ For all those reasons, the tumor HER2 status should probably be "routinely" tested in order to optimize the management of breast cancer patients. Nevertheless, some points remain to be elucidated, including the optimal methods of detection of HER2 (immunohistochemistry, Fish). One of the priorities for future research is to standardize HER2 testing, in order to reduce false-positive results and false-negative results and to better identify patients who are most likely going to benefit from Herceptin.
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Platinum is the standard drug in the treatment of patients with ovarian cancer. The sample of more than 2,000 patients enrolled in randomised trials and 2 meta-analyses were largely sufficient to prove that carboplatin and cisplatin are equally effective. Carboplatin dose adaptation according to renal function and AUC decreases drug induced thrombopenia and has allowed carboplatin to be used widely and safely. ⋯ The carboplatin-paclitaxel regimen can be safely administered every 3 weeks in an outpatient setting assuring a better quality of life than the combination of cisplatin and paclitaxel with equal efficacy. Carboplatin-paclitaxel has thus recently become the standard chemotherapy regimen for patients with advanced ovarian cancer. Forthcoming results of ongoing trials will determine if high carboplatin doses with peripheral hematopoeitic stem cell support in consolidation after first line treatment can benefit patients with advanced disease.
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Carboplatin differs from cisplatin by its pharmacokinetics and toxicity profile. Carboplatin is mainly eliminated by the kidneys and its dose-limiting toxicity is the bone marrow suppression. Myelosuppression of carboplatin is more closely correlated with the area under the curve (AUC) of ultrafiltrable plasma concentration versus time to which a patient is exposed, than it is with the administered dose. ⋯ When carboplatin is given by reiterated administrations within each course, it is possible to adjust the last doses according to a limited number of blood samples following the first infusion and a Bayesian analysis of the observed plasma concentrations. These methodologies are more complex, but they may be useful for the intensification protocols. Carboplatin is still the only cytotoxic drug for which dose is individualised not according to the body surface area but according to pharmacokinetic parameters.
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Carboplatin is a cytotoxic drug used in non-small cell and small cell lung cancer. Its role in advanced disease, but also in combination with radiotherapy, in neoadjuvant treatment and in the treatment approach in elderly patients is reviewed. New cytotoxic drug combinations are described.
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The use of carboplatin has become frequent in children solid tumours because of lower renal and otologic risks as compared to cisplatin. The efficacy of carboplatin has mainly been demonstrated when used in combination with other cytotoxic drugs: few phase II studies of carboplatin alone have been published in children. ⋯ Formula have been developed specifically in children to allow a determination of the prescribed dose using a targeted "area under the curve" rather than dose in mg/m2, which allows a better individual therapeutic adaptation. Long term follow-up after carboplatin treatment in childhood is mandatory mainly because of the mutagenic and hypofecondity potential risks.