Bulletin du cancer
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About forty years ago, immuno-targeting of antitumor drugs has been addressed as a way to improve their selectivity towards tumor cells. Despite the wide display of researches to solve inherent problems within this approach, rare were the immuno-conjugates which reached the clinical level. In any case, none of them was introduced in chemotherapy. ⋯ It was also due to the design of the Adept concept. This antibody-directed enzyme prodrug therapy is based upon the use of monoclonal antibody to target an enzyme at the tumor cell surface which ultimately is expected to selectively deliver an antitumor drug from a suitable inactive prodrug. In both cases, clinical trials are in progress and one can expect that, at least, some immuno-conjugates will be soon introduced in cancer chemotherapy.
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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.