Phase II study of exatecan mesylate (DX-8951f) as first line therapy for advanced non-small cell lung cancer

Background: Exatecan mesylate (DX-8951f) is a water soluble analogue of camptothecin that inhibits topoisomerase I. This multi-centre phase II study evaluated the activity of single agent exatecan in previously untreated patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Patients with histologically or cytologically proven stage IIIb or IV NSCLC were treated with exatecan 0.5 mg/m2 per day by 30 min intra-venous (i.v.) infusion for 5 days every 3 weeks to a maximum of six cycles. Measurable disease was documented prior to study entry and patients were re-staged every two cycles. Pharmacokinetic (PK) sampling was performed during cycle one. Results: 39 patients (32 patients ECOG performance status 0 or 1; 29 male and ten female; mean age 63 years) were entered into the study. Thirty-three completed at least two cycles of exatecan and 11 completed six cycles. Two patients (5.1%, 95% C.I. 0.3–21.3%) had a partial response, 7 (18.0%) minor response and 8 (20.5%) stable disease. Median time to tumour progression (TTP) was 88 days and median overall survival 262 days. The main toxicity was reversible neutropenia. PK analysis of exatecan demonstrated a mean clearance of 2.28 l/h per m2, volume of distribution 18.2 l/m2 and mean elimination half-life of 7.9 h. Conclusions: Exatecan mesylate has limited activity in advanced NSCLC and is not recommended for further evaluation as a single agent in this tumour type. PK data from this trial supports results established in phase I studies.