In the past several years, medical oncologists have become increasingly aware that a subset of patients with advanced non-small-cell lung cancer (NSCLC) may benefit from second-line chemotherapy after the failure of first-line therapy. Most of the data in support of the use of second-line chemotherapy has been with docetaxel(Drug information on docetaxel) (Taxotere).
Docetaxel as a first-line agent for advanced NSCLC showed consistent response rates in phase II trials that ranged from 23% to 38%.[1-5] Average median survival is 39 weeks and 1-year survival is 34%. Docetaxel also has been systematically evaluated in the second-line setting for NSCLC patients whose disease has progressed or failed to respond to first-line platinum-based chemotherapy. Objective radiographic responses were consistently seen in four phase II studies of docetaxel in the second-line setting, and ranged from 16% to 22%.[4-8] Favorable survival rates were noted as well in these trials; the median survival rate ranged from 5.8 to 9.8 months, and the estimated 1-year survival rate ranged from 25% to 44% (Table 1).[4,6-8]
The most compelling evidence to support docetaxel’s activity in the second-line treatment of NSCLC comes from two large randomized phase III trials that compared docetaxel with either best supportive care (TAX 317)  or a comparator regimen of chemotherapy (TAX 320)  (Figure 1).
The TAX 317 trial was a multicenter international trial of second-line chemotherapy with docetaxel reported by Shepherd.[9,11] Eligible patients had advanced NSCLC that had progressed during or after one or more platinum-containing chemotherapy regimens. There was no restriction on the number of prior chemotherapy cycles or regimens, and there was no restriction on the prior chemotherapy agents permitted (with the exception that patients with prior paclitaxel(Drug information on paclitaxel) exposure were excluded). Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Patients with treated brain metastases were included in the trial.
Eligible patients were stratified by their best response to prior platinum-based chemotherapy and performance status and then randomly assigned to receive either docetaxel every 3 weeks or best supportive care. The initial trial design called for a docetaxel dose of 100 mg/m² (D100) as a 1-hour IV infusion every 3 weeks. However, because of an unexpectedly high occurrence of adverse events occurring at this dose level, the protocol was subsequently modified to a docetaxel dose of 75 mg/m² (D75) every 3 weeks.
A total of 204 patients were enrolled in this trial: 49 received docetaxel at 100 mg/m², 55 received docetaxel at 75 mg/m², and 100 received best supportive care. Patient characteristics and updated results are summarized in Table 2. About 80% of patients had stage IV disease, and nearly 25% of patients had a performance status of 2. The demographics with regard to age and gender were typical for this patient population and were well balanced among the treatment groups. The predominant histology was adenocarcinoma. One-quarter of patients had received two or more prior chemotherapy regimens before enrollment.
Partial response was observed in 6% of patients treated with docetaxel (either dose level), and another 40% of patients had stable disease. The median response duration was 26 weeks. Time to progression favored treatment with docetaxel vs best supportive care. The median time to progression was 12.3 weeks with D75 vs 7 weeks with best supportive care (P = .004).