Taxotere: from preclinical to clinical pharmacology

Taxotere (Docetaxel) (TXT) is the first active hemisynthetic taxane with specific properties in part related to the hydrophobic domain (3’ phenyl group) and the polar functions of the C13 lateral chain. In the purified tubulin test as well as in experimental tumors TXT (1) is 2–12 times more active than paclitaxel (TAX); (2) retains activity in some tumors overexpressing Gp 170; (3) shows only partial cross resistance with TAX. In humans 100 mg/m2/3 weeks has been defined as the optimal schedule with > 80% neutropenia, anaphylactoid type reactions, and cumulative skin toxicity and fluid retention syndrome. The latter are in part prevented by corticoseroid premedication. A striking activity was observed in patients with advanced breast cancer in pts with prior chemotherapy (CT) for metastatic progression RR was 50%; it was 48% in anthracyclin resistant pts and 39% in anthracyclin refractory pts with a response duration of 25–28 weeks in these studies. In pts with NSCLC whether previously treated or not RR were close to 20%. Other tumors (Head and Neck, pancreatic, NHL) appeared sensitive although confirmation is required. Taxotere appears a promising new agent which should be part of combination regimens in particular for breast cancer patients.