Phase II trial with ISIS 5132 in patients with small-cell (SCLC) and non-small cell (NSCLC) lung cancer. A European Organization for Research and Treatment of Cancer (EORTC) Early Clinical Studies Group Report

Two multicentre phase II trials were designed to determine if tumour respon ses can be achieved in progressive small-cell lung cancer (SCLC) or non-sma ll cell lung cancer (NSCLC) patients treated with ISIS 5132, an inhibitor o f C-nif kinase mRNA expression (CGP 69846A; ISIS Pharmaceuticals Inc, Carls bad, CA), and to further characterise the safety of the compound. Between A ugust 1998 and November 1999, 26 patients (18 NSCLC, 8 SCLC) were entered. Out of these, 23 were eligible, 22 (18 NSCLC, 4 SCLC) were treated with ISI S 5132 (2 mg/kg/day, 21 days continuous intravenous (i.v.) infusion every 4 weeks) and were evaluable for toxicity and 18 (15 NSCLC, 3 SCLC) were eval uable for efficacy. For the whole group haematological toxicity did not exc eed grade 2. One patient experienced a grade 4 increased prothrombin time. Non-haematological toxicity was mild to moderate, with the observation of a sthenia. and nausea and vomiting. Progressive disease (PD) was diagnosed in 10 patients (8 NSCLC and 2 SCLC). 8 more patients (7 NSCLC, 1 SCLC) were c onsidered as treatment failures. In conclusion, this study using ISIS 5132 with this dose and schedule of administration excludes a 20% response rate with 95% confidence intervals for NSCLC and cannot draw any conclusions for SCLC patients as only a few were involved in the study. (C) 2001 Elsevier Science Ltd. All rights reserved.