A dose-escalation study of irinotecan (CPT-11) in combination with cisplatin in patients with advanced non-small cell lung cancer previously treated with a docetaxel-based front line chemotherapy

Purpose: A phase I study was conducted to determine the maximum-tolerated d ose (MTD) and the dose-limiting toxicities (DLTs) of a CPT-11 plus cisplati n combination as salvage treatment in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Twenty-two patients with histol ogically confirmed NSCLC, who had failed taxotere-based front-line chemothe rapy, were enrolled. The patients' median age was 61 years, 19 (86%) were m ale, and 17 (77%) had a performance status (World Health Organization (WHO) ) 0-1. CPT-11 was administered as a 60-min i.v. infusion at a fixed dose of 100 mg/m(2) on day 1 and at escalating doses on day 8, starting from 100 m g/m(2) with increments of 10 mg/m(2); cisplatin was administered at a fixed dose of 80 mg/m(2) on day 8, 2 h after CPT-11 administration. Treatment wa s repeated every 3 weeks. Results: At the dose of CPT-11 120 mg/m(2), three out of four enrolled patients presented DLTs (grade 4 neutropenia, febrile neutropenia and delayed diarrhea); the addition of G-CSF at this level did not permit further dose-escalation. Grade 3/4 neutropenia was observed in 12 (18%) cycles, febrile neutropenia in four (6%), and grade 3/4 thrombocyt openia in four (6%). Grade 3/4 diarrhea was seen in six (29%) patients, and grade 2/3 nausea and vomiting in 12 (57%), Neurotoxicity grade 2 was obser ved in six (29%) patients and grade 3 in one (5%). Other toxicities were mi ld. The MTD was CPT-11 100 mg/m(2) on day 1 and 110 mg/m(2) on day 8 in com bination with CDDP 80 mg/m2 on day 8. Among 12 patients evaluable for respo nse, partial response was achieved in two (16.7%) patients and stable disea se in five (41.7%). Conclusion: The combination of CPT-11 and cisplatin has substantial but manageable toxicity and marginal activity as salvage treat ment of patients with NSCLC who have failed taxotere-based front-line chemo therapy; further investigation is warranted to define its precise role in t he second-line setting. (C) 2000 Elsevier Science Ireland Ltd. All rights r eserved.