Commentary on Abstracts #976, #1008, and #1964

These abstracts examine the use of single-agent docetaxel (Taxotere), an antimicrotubule agent and one of the most active drugs against NSCLC currently available, in the first- and second-line settings.

Roszkowski (abstract #976) presents the results of a multicenter trial that enrolled 207 previously untreated patients with advanced NSCLC. These patients were randomized in a 2:1 fashion to receive either single-agent docetaxel 100 mg/m² every 3 weeks, or best supportive care (BSC). The response rate of docetaxel was 20%; no toxicity data are presented. Results of this study revealed a survival advantage for docetaxel-treated patients at 12 and 20 months, but not at 6 months. The magnitude of the survival benefit at 1 year (9%) is comparable to that seen with cisplatin (Platinol)-based combination chemotherapy in the meta-analysis described above. However, median survival data are not presented, so caution is indicated in interpreting the results. Patients receiving docetaxel had symptomatic improvement, with statistically significant reductions in dyspnea, pain, and requirements for analgesics and palliative radiotherapy.

Phase II trials have consistently demonstrated that docetaxel has activity in the second-line treatment of NSCLC (J Clin Oncol 18:131-135, 2000). Shepherd et al (J Clin Oncol 18[10]:2095-2103, 2000) reported the results of the first randomized trial comparing chemotherapy to BSC in the second-line setting, and Fossella et al (J Clin Oncol 18[12]:2354-2362, 2000) compared docetaxel to the investigators' choice of vinorelbine or ifosfamide in this setting. Taken together, these three randomized studies (abstract #976

and the studies of Shepherd et al and Fossella et al) support the use of single-agent docetaxel to improve survival, quality of life, and disease-related symptoms in both the first- and second-line settings in medically suitable patients. Although toxicity data are not presented by Roszkowski, the trials by Shepherd and Fossella, and prior experience, have shown that single-agent docetaxel is well tolerated.

The data presented by Wilke et al (abstract #1008) describe the experience with docetaxel from over 100 centers on several continents, and confirm high activity, a reproducible toxicity profile, and good tolerability. Although no survival data are presented, the available data are reassuring that the results obtained in other trials with more rigid eligibility criteria are generalizable to the wider lung cancer population seen in practice.

A large proportion of patients with non–small-cell lung cancer have comorbid conditions that make them poor candidates for combination chemotherapy. It is unclear how best to treat these patients. Historically, they have often been offered best supportive care.

McKay and colleagues present the results of a study using weekly docetaxel in patients older than 65 and/or with poor performance status (abstract #1964). When given weekly, docetaxel has minimal myelosuppression and an altered toxicity profile compared to every-3-week dosing, and is generally well tolerated. A total of 39 previously untreated patients were enrolled in this phase II study. Their median age was 71 years, and 41% had performance status 2. Dexamethasone premedication was used. The regimen was only mildly toxic. No grade 4 hematologic toxicity was seen, with grade 3 anemia and leukopenia seen in 13% and 8%, respectively. Grade 3/4 nonhematologic toxicity was rare, with neuropathy and a hypersensitivity reaction each seen in only one patient; no fluid retention was observed.

One complete and six partial responses were seen, for an overall response rate of 19%. An additional 13 patients (36%) had stabilization of their disease. The median duration of response was 8 months, the median survival 5 months, and the 1-year overall survival proportion was 28%. Although these results appear roughly comparable to every-3-week dosing of docetaxel, confirmatory studies are needed before widespread use of weekly docetaxel is recommended.