Platinum compounds-taxanes pharmacologic interactions

Taxoids and platinum derivatives display a true activity against many types of solid tumors. Their relatively non overlapping toxicity profiles and th eir different mechanisms of action made their combination attractive. Actua lly, the frequence and the severity of the toxicity appeared schedule-depen dent. Thus, cisplatin-paclitaxel combination generates more neutropenia, wh en cisplatin is delivered before paclitaxel. Cisplatin reduces paclitaxel p lasma clearance, bat the interference appears more due to pharmacodynamic i nteraction. Cisplatin-induced DNA adducts are more limited when paclitaxel is administered before cisplatin. Tolerance is better but we cannot conclud e in term of efficacy. Cisplatin and docetaxel interaction and schedule-dep endence appear much less obvious in term of toxicity. On the other hand, th rombopenia carboplatin-induced is significatively decreased when combined t o paclitaxel. In that case, the interaction is clearly pharmacodynamic. The correlation curve of thrombopenia and platinum in plasma area under the cu rve is modified and shows an increased tolerance of platelets to carboplati n. The cause remains unknown, to our knowledge. The interaction protects on ly the platelets. No data is available for docetaxel and carboplatin combin ation. A better knowledge of the metabolism and the interactions of these t wo drug families is quite necessary for better using them in combination, b oth in term of efficacy and tolerance.