The 1-year survival for patients with metastatic non-small-cell lung cancer is only around 35%. We are evaluating the combination of irinotecan (Camptosar) and carboplatin (Paraplatin) in patients with stage IIIB and IV non-small-cell lung cancer. The first five patients received irinotecan, 250 mg/m2 over 90 minutes followed by carboplatin at an area under the concentration-time curve of 5 over 1 hour1 The dose of irinotecan was subsequently reduced to 200 mg/m2 in view of febrile neutropenia in one of five patients. Chemotherapy cycles are repeated every 21 days. Patients are reevaluated every two cycles. Of a planned 42 patients, 37 have been enrolled so far. Of the 37 enrolled patients, 25 received at least two cycles, 20 received at least four cycles, and 12 received all six planned cycles. Grade 4 neutropenia (absolute neutrophil count <500) occurred in 10 patients and 19 treatment cycles. Two of these patients also had grade 4 diarrhea. Thirty-six cycles (30%) were delayed for neutropenia, six of which occurred among the first five patients who received irinotecan at 250 mg/m2. Best response to therapy included 7 partial responses (23%), 11 stable disease (37%), with 12 patients having progressive disease (40%). The regimen of irinotecan and carboplatin administered once every 3 weeks is tolerable and convenient, with early evidence of activity. The main toxicity is hematologic. This study is ongoing and actively accruing patients.