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 noncomparative trials, continuous infusion of
paclitaxel 110 to 300 mg/m2 over 3 to 96 hours every 3 to 4 weeks produced a complete or partial response in 16 to 48% of patients with
ovarian cancer and 25 to 61.5% of patients with metastatic
breast cancer, many of whom were refractory to treatment with
cisplatin or
doxorubicin, respectively. 23 to 100% of patients with
ovarian cancer achieved complete or partial responses with
paclitaxel in combination with
cisplatin,
carboplatin,
cyclophosphamide,
altretamine and/or
doxorubicin. Similarly, response rates of 30 to 100% were observed with
paclitaxel plus
doxorubicin,
cisplatin,
mitoxantrone and/or
cyclophosphamide in patients with metastatic
breast cancer. Comparative trials in patients with advanced
ovarian cancer showed
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 more effective than
mitomycin in 50 patients with previously untreated
breast cancer (partial response in 20 vs 4% of patients).
Paclitaxel therapy also produced promising results in patients with advanced
squamous cell carcinoma of the head and neck,
malignant melanoma, advanced
non-small cell lung cancer (NSCLC),
small cell lung cancer (SCLC),
germ cell cancer, urothelial
cancer, oesophageal
cancer,
non-Hodgkin's lymphoma or
multiple myeloma, and was successfully combined with
cisplatin,
carboplatin and/or
etoposide in patients with NSCLC, SCLC or advanced
squamous cell carcinoma of the head and neck.
Hypersensitivity reactions were initially a concern with administration of
paclitaxel, although current dosage regimens have reduced the incidence of these events to less than 5%. The major dose-limiting adverse effects of
paclitaxel are leucopenia (
neutropenia) and
peripheral neuropathy. Other haematological toxicity was generally mild.
Cardiac toxicity was reported in small numbers of patients and most patients developed total
alopecia. Several aspects of
paclitaxel use remain to be clarified, including the optimal treatment schedule and infusion time, confirmation of the tolerability profile and efficacy of combination regimens in an expanded range of
malignancies. Long term follow-up of
paclitaxel recipients will also allow the effects of the
drug on patient survival to be determined. Nevertheless,
paclitaxel is a promising addition to the current
therapies available, with significant activity reported in patients with advanced ovarian or
breast cancer or other types of
tumors.(ABSTRACT TRUNCATED AT 400 WORDS)