Cumulative experience with single-agent paclitaxel in advanced metastatic non-small cell lung cancer (NSCLC) suggests that it is a highly active cytotoxic agent. The consistent finding of a 35% to 40% 1-year survival rate is notable. The major toxicities include neutropenia, neuropathy, and myalgia/arthralgia syndrome. Paclitaxel has been used in combination with several other nonplatinum agents for the treatment of NSCLC. Order of administration and schedule are clearly relevant in these combinations. For example, in one study, etoposide and paclitaxel given simultaneously proved ineffective, with substantial grade IV neutropenia Another schedule with an identical dose of etoposide, given daily for 3 days, followed by paclitaxel achieved a response rate of 41%, with markedly diminished neutropenia A variety of phase I studies have evaluated gemcitabine/paclitaxel, with response rates ranging from 22% to 30%. Paclitaxel/vinorelbine also has proven feasible in both small cell lung cancer and NSCLC, with a response rate of 17%. Investigators have combined paclitaxel with ifosfamide at full dose with response rates of 21% and 23%. The three-drug nonplatinum combination of paclitaxel/ifosfamide/vinorelbine also has been studied. The maximum tolerated dose for ifosfamide was 1.2 g/m2 on days 1 through 3, for vinorelbine 20 mg/m2 on days 1 through 3, and for paclitaxel 175 mg/m2 on day 1. The response rate of 16% was disappointing. Median survival was 6.1 months and toxicity was substantial. Paclitaxel/non-platinum combinations may prove to be reasonable alternatives for NSCLC patients who cannot tolerate cisplatin and for relapsed patients and patients with compromised performance status.