[Phase II studies of gemcitabine for non-small cell lung cancer in Japan]

To determine the activity and toxicity of gemcitabine in non-small cell lung cancer, three phase II studies of single agent gemcitabine have been conducted between 1990 and 1994. In an early phase II study, gemcitabine was administered of 800 mg/m2 on day 1, 8, 15 every four weeks (step I), and 1,000 mg/m2 (step II). Response was observed in 3 of 13 patients with previously untreated non-small cell lung cancer, although there was no responders in the previously treated patients. Late phase II studies were performed at 20 (group A) and 24 (group B) Japanese institutions to confirm the efficacy and safety of gemcitabine administered alone in patients with non-small cell lung cancer. Seventy-three patients (group A) and 67 patients (group B) were entered into these studies. All patients had no previous chemotherapy and had measurable disease. Gemcitabine was administered at a starting dose of 1,000 mg/m2/wk for 3 weeks followed by a week of rest. The dose was escalated to 1,250 mg/m2 if severe toxicity was not seen in the previous course. Nineteen of 73 patients (26%) had a partial response in group A. Of 67 patients, 14 (20.9%) showed a partial response in group B. Grade 3 or greater toxicities included anemia (20.5%) and leukopenia (9.6%) in group A, and in 13.4% and seven 10.4% in group B, respectively. And grade 3 thrombocytopenia was observed in 1.4%. Other toxicities including hepatic toxicity, fatigue, nausea/vomiting, and fever were mild and transient. Pulmonary toxicity was observed in five patients, two of whom died of ARDS. The median durations of response were 19.6 weeks in group A and 20 weeks in group B, and median survival times were 44 and 39 weeks, respectively. In conclusion, gemcitabine is an active agent against non-small cell lung cancer with very mild toxicities. These results suggest that gemcitabine has potential utility in advanced non-small cell lung cancer on an outpatient basis. Further trials in combination with other active agents are warranted.