TORINO, Italy-Combination therapy with gefitinib (Iressa) and gemcitabine (Gemzar) produced disease control in 45.7% of elderly patients with advanced non-small-cell lung cancer (NSCLC), according to Giorgio V. Scagliotti, MD, of the University of Turin, Torino, Italy, reporting results of a phase II Italian multicenter study (abstract 7081). The study also found that patients were better able to tolerate gefitinib/gemcitabine than a gefitinib/vinorelbine (Navelbine) combination. The study included 59 elderly patients with chemonaive stage IIIB/IV NSCLC. All patients were treated with gefitinib (250 mg/day orally until progression), plus either vinorelbine (30 mg/m² IV, arm A) or gemcitabine (1,200 mg/m² IV, arm B). For unexplained reasons, the two study arms differed in a number of characteristics. Male patients accounted for 58% of arm A vs 80% of arm B, and squamous histology characterized 17% of arm A vs 31% of arm B. Drugs were given on days 1 and 8 every 21 days for six cycles. The primary endpoint was response rate. Arm A was closed after 21 of the first 24 patients (87.5%) had grade 3 or 4 adverse events, Dr. Scagliotti re ported. These included 72% grade 3 or 4 neutropenia and treatment-related deaths (one sudden cardiac arrest, one grade 4 neutropenia with septic shock and cerebral infarction, and one grade 4 diarrhea followed by cardiac arrest). "Of the 12 nonevaluable patients, 6 had withdrawn from the study, 5 had died, and 1 had an unconfirmed diagnosis of NSCLC," Dr. Scagliotti said. In both arms, the most common gefitinib-related adverse event was skin toxicity, mainly grade 1-2. In arm B, 11.4% of patients experienced grade 3- 4 neutropenia and 8.6% had thrombocytopenia , compared with 0 in arm A. Grade 3-4 asthenia and diarrhea were more common in arm A, with both those adverse events occurring among 12% in arm A vs 5.7% in arm B. Dr. Scagliotti also reported one case of grade 4 elevated transaminase levels. Responses and Duration Among the 27 patients in arm A (gefitinib/vinorelbine) 1 (4%) had a complete response (CR), 3 (12%) had partial responses (PR), 7 (28%) had stable disease (SD), 6 had progressive disease (PD), and 7 patients were not evaluable (see Table 1). Median duration of response on arm A was 274 days; median time to progression (TTP) was 91 days; median survival was 371 days; and 63% of patients were alive at 6 months. Responses and Duration Among the 27 patients in arm A (gefitinib/vinorelbine) 1 (4%) had a complete response (CR), 3 (12%) had partial responses (PR), 7 (28%) had stable disease (SD), 6 had progressive disease (PD), and 7 patients were not evaluable (see Table 1). Median duration of response on arm A was 274 days; median time to progression (TTP) was 91 days; median survival was 371 days; and 63% of patients were alive at 6 months. "In elderly patients with advanced NSCLC, vinorelbine plus gefitinib was active but toxicity was unacceptable, while gemcitabine plus gefitinib was safe, and a remarkable percentage of patients achieved disease control," Dr. Scagliotti concluded.