Two phase III trials were conducted using docetaxel (Taxotere), administered every 3 weeks, as second-line treatment of non-small-cell lung cancer (NSCLC) in patients previously treated with platinum-based chemotherapy. In the TAX 317 trial, 204 patients were randomized to receive either docetaxel (49 received 100 mg/m2 and 55 received 75 mg/m2) or best supportive care (100 patients). Median survival was 7.5 months with docetaxel at 75 mg/m2 (D75) vs 4.6 months for best supportive care (P = .010); and 1-year survival was 37% for D75 vs 11% for best supportive care (P = .010). Quality-of-life analysis also showed statistically significant improvement in disease-related symptoms with docetaxel vs best supportive care. In the TAX 320 study, 373 patients were randomized to receive docetaxel at 100 mg/m2 (D100), docetaxel at 75 mg/m2 (D75), or a control arm of either vinorelbine (Navelbine) or ifosfamide (Ifex) (V/I). Partial response rates were 11.9% with D100 and 7.5% with D75 vs 1% with V/I (P values: .001 [D100] and .036 [D75]). Median response duration was over 7 months. One-year survival was 32% with D75 vs 19% in V/I (P = .025). Prior paclitaxel exposure had no bearing on the response rate and survival advantage of second-line treatment with docetaxel. Response rates to docetaxel were equivalent in the cohort of patients who had received prior paclitaxel (10.5%) and the group ofpatients who had not received prior paclitaxel (8.5%). The 1-year survival rates for patients with no prior paclitaxel therapy were 33% (D75) vs 20% (V/I); and the 1-year survival rates for patients who had received prior paclitaxel were 30% (D75) vs 17% (V/I). In conclusion, two large randomized phase III trials of second-line chemotherapy for NSCLC have shown significant differences favoring docetaxelfor response rate, time to progression, survival, and quality of life. Prior paclitaxel did not decrease the likelihood of response to docetaxel, nor did it lessen the survival advantage seen with docetaxeL Docetaxel offers a clinically meaningful benefit in this setting, with manageable toxicity. Based upon the observed response rates, survival, impact on quality of life, and toxicity profile, the optimal dose of docetaxel in this pretreated population is 75 mg/m2 every 3 weeks.