Commentary on Abstract #1916

The Southwest Oncology Cooperative Group (SWOG) conducted a study in which single-agent docetaxel (Taxotere) was used as “consolidation” therapy following concurrent chemoradiotherapy (abstract #1916). A previous SWOG study (S90-19) (Proc Am Soc Clin Oncol 16: 446a [abstract 1600], 1997) established that chemotherapy with cisplatin (Platinol)/etoposide could be given concurrently with definitive thoracic irradiation both safely and effectively. In this earlier trial, following the completion of irradiation, two additional cycles of cisplatin/etoposide were given.

The current study utilizes the concurrent chemoradiotherapy schedule from S90-19, but substitutes three cycles of single-agent docetaxel as the consolidation chemotherapy. The rationale for this is the good single-agent activity of docetaxel in both the first- and second-line setting, and the hypothesis that the introduction of a new drug may eradicate cells resistant to cisplatin and etoposide. Docetaxel was to be given as a 1-hour intravenous infusion every 3 weeks. The dose for the first cycle was 75 mg/m², with escalation to 100 mg/m² for the final two cycles. The current phase II trial (S95-04) enrolled 83 patients with pathologically documented stage IIIB (either T4 or N3) disease who were suitable for an attempt at combined-modality curative therapy.

Toxicity of the induction chemoradiotherapy included grade 4 neutropenia (18%), thrombocytopenia (5%), and esophagitis (6%), but was not greater than past SWOG experience with this regimen. No fatalities were seen during this phase of therapy. Sixty-nine of 83 patients (83%) went on to receive consolidation with docetaxel. Overall, docetaxel was well tolerated. The majority of patients could not tolerate an escalation of the docetaxel dose above 75 mg/m2. Grade 4 neutropenia was seen in 56% of patients, but only one episode of febrile neutropenia occurred, consistent with the brief period of neutropenia caused by docetaxel. However, three deaths from pneumonitis occurred during the consolidation phase. Whether this is attributable to radiation, docetaxel, or the combination of the two cannot be ascertained.

The overall response rate to the entire protocol was 63%, with 4% complete responses. Only 9% of patients had progressive disease at the completion of therapy. The median progression-free survival was 15 months, and the median overall survival was 22 months. The 1- and 2-year survivals were 78% and 50%, respectively. When compared to patients treated on S90-19, who were a comparable population in terms of age, sex, performance status, and stage, the current protocol resulted in superior median, 1-, and 2-year survival proportions (22 vs 15 months, 78% vs 50% and 50% vs 34%, respectively).

Overall, this trial has demonstrated very promising results in a group of patients with a historically poor prognosis, and it appears to be generally well-tolerated. Given the recent data implying that there may be an advantage to concurrent chemoradiotherapy vs sequential chemotherapy and irradiation (J Clin Oncol 17: 2692-2699, 1999), this approach offers the possibility of improved outcomes in this patient population. Additional study of this promising and creative strategy, to better define efficacy and toxicity, is warranted before it is adopted as a standard.