Taxanes as first-line therapy for advanced non-small cell lung cancer: A systematic review and practice guideline

This evidence-based practice guideline on the use of paclitaxel (Taxol) or docetaxel (Taxotere) as first-line treatment for patients with advanced non-small cell lung cancer who are candidates for palliative first-line chemotherapy is based on a systematic search and review of literature published in full or in abstract form between 1985 and April 2005. Forty-five randomized trials, including 11 abstracts, were reviewed and clinicians in the province of Ontario, Canada, provided feedback on a draft version of the guideline. Two phase III trials detected a statistically significant survival advantage for a taxane (paclitaxel or docetaxel) with best supportive care versus best supportive care alone. Among the nine fully published phase III trials comparing platinum-based chemotherapies, taxane-platinum combinations achieved higher response rates compared with older chemotherapy combinations, although significantly longer survival was observed only for docetaxel-cisplatin compared with vindesine-cisplatin. Response rates and survival were generally not significantly different for taxane-platinum combinations compared with other current chemotherapy combinations, although the toxicity profile of the regimens varied. However, in one large trial, improved tumor response and modest survival and quality of life benefits were associated with docetaxel-cisplatin compared with vinorelbine-cisplatin. No statistically significant survival differences were detected in the three fully published phase III trials comparing a taxane-gemcitabine combination with a taxane-platinum regimen. RECOMMENDATIONS: (i) paclitaxel or docetaxel combined with cisplatin is recommended as one of a number of chemotherapy options for the first-line treatment of advanced non-small cell lung cancer in patients with a good performance status; (ii) carboplatin may be combined with a taxane if a patient is unable or unwilling to take cisplatin; (iii) a taxane-gemcitabine combination may be considered for patients with a contraindication to cisplatin and carboplatin; (iv) no firm recommendation can be made on the optimal dose and schedule of taxane-based chemotherapy; however, commonly used regimens include cisplatin 75 mg/m2 combined with either docetaxel 75 mg/m2 or paclitaxel 135 mg/m2 (24-h infusion) and carboplatin AUC 6 combined with paclitaxel 225 mg/m2 (3-h infusion); (v) a single-agent taxane may be used if combination chemotherapy is considered inappropriate.