Abstract

PURPOSE:

A phase I study was conducted to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of a CPT-11 plus cisplatin combination as salvage treatment in patients with advanced non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS:

Twenty-two patients with histologically confirmed NSCLC, who had failed taxotere-based front-line chemotherapy, were enrolled. The patients' median age was 61 years, 19 (86%) were male, 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/m2 on day 1 and at escalating doses on day 8, starting from 100 mg/m2 with increments of 10 mg/m2; cisplatin was administered at a fixed dose of 80 mg/m2 on day 8, 2 h after CPT-11 administration. Treatment was repeated every 3 weeks.

RESULTS:

At the dose of CPT-11 120 mg/m2, 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 thrombocytopenia 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 observed in six (29%) patients and grade 3 in one (5%). Other toxicities were mild. The MTD was CPT-11 100 mg/m2 on day 1 and 110 mg/m2 on day 8 in combination with CDDP 80 mg/m2 on day 8. Among 12 patients evaluable for response, partial response was achieved in two (16.7%) patients and stable disease in five (41.7%).

CONCLUSION:

The combination of CPT-11 and cisplatin has substantial but manageable toxicity and marginal activity as salvage treatment of patients with NSCLC who have failed taxotere-based front-line chemotherapy: further investigation is warranted to define its precise role in the second-line setting.