PHASE-II AND PHARMACOKINETIC STUDY OF PACLITAXEL THERAPY FOR UNRESECTABLE HEPATOCELLULAR-CARCINOMA PATIENTS

Hepatocellular carcinoma (HCC) is a common lethal disease in Asia and there is no effective chemotherapy. Identification of new effective dr ugs in the treatment of inoperable HCC is urgently need. This is a pha se II clinical study to investigate the efficacy, toxicity and pharmac okinetics of paclitaxel in HCC patients. Twenty patients with measurab le, unresectable HCC, normal serum bilirubin, normal bone marrow and r enal functions were studied. Paclitaxel 175 mg m(-2) was given intrave nously over 3 h every 3 weeks, No complete or partial responses were o bserved. Five patients had stable disease. Major treatment toxicities (grade 3-4) were neutropenia (25%), thrombocytopenia (15%), infection (10%) and allergy (10%). Treatment-related deaths occurred in two pati ents. The median survival was 12 weeks (range 1-36). Paclitaxel is met abolized by the liver and the pharmacokinetics of paclitaxel in cancer patients with liver involvement or impairment may be important clinic ally. Pharmacokinetic study was completed in 13 HCC patients. The pacl itaxel area under the curve was significantly increased (P < 0.02), cl earance decreased (P < 0.02) and treatment-related deaths increased (P = 0.03) in patients with hepatic impairment. In conclusion, paclitaxe l in this dose and schedule has no significant anti-cancer effect in H CC patients. Paclitaxel should be used with caution in cancer patients with liver impairment.