[Pharmacology of platinum analogs-taxanes interactions]

Taxoids and platinum derivatives display a true activity against many types of solid tumors. Their relatively non overlapping toxicity profiles and their different mechanisms of action made their combination attractive. Actually, the frequency and the severity of the toxicity appeared schedule-dependent. Thus, cisplatin-paclitaxel combination generates more neutropenia, when cisplatin is delivered before paclitaxel. Cisplatin reduces paclitaxel plasma clearance, but the interference appears more due to pharmacodynamic interaction. Cisplatin-induced DNA adducts are more limited when paclitaxel is administered before cisplatin. Tolerance is better but we cannot conclude in term of efficacy. Cisplatin and docetaxel interaction and schedule-dependence appear much less obvious in term of toxicity. On the other hand, thrombopenia carboplatin-induced is significatively decreased when combined to paclitaxel. In that case, the interaction is clearly pharmacodynamic. The correlation curve of thrombopenia and platinum in plasma area under the curve is modified and shows an increased tolerance of platelets to carboplatin. The cause remains unknown, to our knowledge. The interaction protects only the platelets. No data is available for docetaxel and carboplatin combination. A better knowledge of the metabolism and the interactions of these two drug families is quite necessary for better using them in combination, both in term of efficacy and tolerance.