In medically suitable patients with stage III (locally advanced) nonsmall-cell lung cancer, the use of cisplatin(Drug information on cisplatin) (Platinol)-based chemotherapy as induction therapy prior to definitive local therapy has been shown to improve survival (J Natl Cancer Inst 86:673-680, 1994; Ann Intern Med 125:723-729, 1996). This is true regardless of whether the local treatment modality used is surgery or thoracic irradiation. However, because cisplatin therapy is particularly toxic, there is interest in studying other agents in the induction setting. Given its activity in nonsmall-cell lung cancer, docetaxel(Drug information on docetaxel) (Taxotere) is one logical agent to investigate.
Mattson and colleagues (abstract #1890) report the results of an international randomized trial comparing definitive local therapy alone to three cycles of induction chemotherapy with single-agent docetaxel, 100 mg/m² intravenously over 1 hour every 3 weeks, followed by local therapy. A total of 274 patients with stage IIIA or IIIB nonsmall-cell lung cancer were enrolled. Patients were stratified by stage and performance status. The two groups were well balanced for other relevant characteristics. Approximately 20% of patients in each arm underwent surgery, while the remainder had radiotherapy as their local treatment.
The overall response rate to docetaxel therapy was 26%; 39% of patients had stable disease, 20% of patients progressed while on chemotherapy, and 15% of patients were not evaluable. Eighty-one percent of patients received all three planned cycles; however, only 66% received their full treatment (at least two cycles of chemotherapy plus complete local therapy). In the control arm, 87% of patients received their full treatment (complete local therapy only). Reasons for failure to complete the assigned therapy are not given. Toxicity of the induction chemotherapy was relatively mild, although there were two treatment-related deaths from neutropenic sepsis.
In the intent-to-treat analysis, there was no difference in median survival between the two arms (15 months for the induction therapy arm vs 14 months, P = .3). An analysis comparing those patients who successfully received their assigned full treatment implies an advantage to the use of induction therapy with docetaxel (median survival: 21 vs 14 months, P = .0014), and this benefit was apparent in all stage subgroups. However, this type of analysis should be interpreted with caution. The full treatment cohort, by definition, is a group of patients who are selected to do well, compared to those patients who did not complete the induction therapy because of toxicity or progression of their disease following the first cycle of therapy.
This was the first trial to examine the use of a single agent in the induction setting. Despite the good activity of docetaxel in nonsmall-cell lung cancer, it may be that the use of two or more drugs is required to eradicate micrometastatic disease and produce a survival advantage. At the present time, cisplatin-based combination chemotherapy remains the standard of care for medically suitable patients in the induction setting.
Vincent A. Miller, MD