SEATTLE-The largest prospective trial of patients with bronchoalveolar carcinoma (BAC) showed that gefitinib(Drug information on gefitinib) (Iressa) shows single-agent activity and that women tend to survive longer on the drug than men. Howard L. West, MD, of the Swedish Cancer Institute in Seattle reported results of the Southwest Oncology Group (SWOG) study S0126 (abstract 7014). Although considered to be poorly responsive to conventional chemotherapy, BAC had not been widely studied despite the fact that it is becoming more common, especially among young, nonsmoking women, Dr. West noted. "But there were anecdotal reports of rapid and remarkable radiographic responses to gefitinib, some quite long-lasting," he said. The study included 145 patients (136 evaluable) with advanced BAC, including 102 who had no prior chemotherapy. There was no requirement that the patients' tumors express the epithelial growth factor receptor (EGFR), the drug's target. The main study objective was to determine potential clinical, radiographic, pathologic, and molecular markers predictive of outcome under the influence of gefitinib therapy. The primary study endpoint was overall survival. Secondary endpoints included progression-free survival (PFS), the response rate by RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and toxicity. Patients were treated with daily oral doses of gefitinib (500 mg) until there was evidence of progression or prohibitive toxicity. Dr. West reported that the response rates were 19% in previously untreated patients (including 6% complete responses) and 9% in previously treated patients. "The clinical benefit rate (complete responses, partial responses, and stable responses) approached 50% in both groups," he said. Median survival was similar in both groups (10 to 12 months), as was median PFS (3 to 4 months). "There was a subset of patients with BAC who experienced prolonged survival with gefitinib. One of the most important variables was gender. Women had a median survival of 19 months compared to 8 months for men," Dr. West said. "This relationship was present for both previously treated and untreated patients." One year survival was about 50% in each subgroup. "A small group of patients continue to have no progression beyond 1 year," Dr. West said. Better Survival With Rash Development of any type of rash was associated with significantly better survival, and patients with grade 1 rash had survival similar to those with grade 2 or 3 rash. "There were no responses among patients who did not develop a rash," Dr. West said. Patients who had never smoked also had better survival. Median survival of nonsmokers has not yet been reached. Toxicity was predominantly an acneiform rash (82%; 11% grade 3 or 4) and diarrhea (69%; 20% grade 3, no grade 4). Fifteen patients (11%) came off trial because of toxicity. Just over one-third had dose reduction to 250 mg/day. Pulmonary toxicity has been a concern with this drug, and there were three deaths among patients in this study that were considered to be probably treatment-related. "In each case, the patient had a worsening of diffuse pulmonary infiltrates and had toxemia of unclear etiology, although it may represent interstitial lung disease," Dr. West told Oncology News International.