PACLITAXEL - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES AND THERAPEUTIC POTENTIAL IN THE TREATMENT OF CANCER

Paclitaxel is a new anticancer agent with a novel mechanism of action. It promotes polymerisation of tubulin dimers to form microtubules and stabilises microtubules by preventing depolymerisation. In noncompara tive trials, continuous infusion of paclitaxel 110 to 300 mg/m(2) over 3 to 96 hours every 3 to 4 weeks produced a complete or partial respo nse in 16 to 48% of patients with ovarian cancer and 25 to 61.5% of pa tients with metastatic breast cancel, many of whom were refractory to treatment with cisplatin or doxorubicin, respectively. 23 to 100% of p atients with ovarian cancer achieved complete or partial responses wit h paclitaxel in combination with cisplatin, carboplatin, cyclophospham ide, altretamine and/or doxorubicin. Similarly, response sates of 30 t o 100% were observed with paclitaxel plus doxorubicin, cisplatin, mito xantrone and/or cyclophosphamide in patients with metastatic breast ca ncer. Comparative trials in patients with advanced ovarian cancer show ed paclitaxel therapy to produce greater response rates than treatment with parenteral hydroxyurea (71 vs 0%) or cyclophosphamide (when both agents were combined with cisplatin) [79 vs 63%]. Paclitaxel was also move effective than mitomycin in 50 patients with previously untreate d breast cancer (partial response in 20 vs 4% of patients). Paclitaxel therapy also produced promising results in patients with advanced squ amous cell carcinoma of the head and neck, malignant melanoma, advance d non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), g erm cell cancer, urothelial cancer oesophageal cancer, non-Hodgkin's l ymphoma or multiple myeloma, and was successfully combined with cispla tin, carboplatin and/or etoposide in patients with NSCLC, SCLC or adva nced squamous cell carcinoma of the head and neck.