A phase II study of 9-aminocamptothecin in advanced non-small-cell lung cancer

Background: 9-Aminocamptothecin (9-AC) is a synthetic analogue of camptothecin. Phase I studies, identified the maximum tolerated dose as 1416 mu g/m(2)/day x 3 as continuous intravenous infusion (CVI) with dose-limiting neutropenia. Patients and methods. Eligible patients had stage IIIB or IV non-small-cell lung cancer (NSCLC) with measurable disease. Patients were initially treated at 1416 mu g/m(2)/d x 3 by CVI followed by granulocyte-colony stimulating factor (G-CSF) support. This dose was decreased to 1100 mu g/m(2)/d after the first 13 patients. Cycles were repeated every 14 days until tumor progression. Results: Fifty-eight patients were treated, thirteen at 1416 mu g/m(2)/d and 45 at 1100 mu g/m(2)/d. Fifty percent had adenocarcinoma and 17% squamous cell carcinoma. Seventy-one percent had stage IV disease. Five patients had a partial response (response duration 9-28 weeks) for an overall response rate of 8.6%, (95% confidence intervals (CI): 2.9%-19%). Median time to progression was 2.3 months and the median survival for the entire study population 5.4 months with a one-year survival rate of 30%. The one-year survival rate for 27 patients who received second line chemotherapy was 56.7%. Toxicities at 1416 mu g/m(2)/d included grade 4 neutropenia and thrombocytopenia in six and five of 13 patients, respectively; at 1100 mu g/m(2)/d these toxicities were observed in 12 and three of 45 patients, respectively. Conclusion. 9-AC has modest single-agent activity in previously untreated NSCLC. Its further evaluation at the dose and schedule employed in this study does not seem indicated. Exploration of more prolonged administration schedules may be warranted.