We conducted a feasibility study of continuous etoposide infusion, which was expected to suppress DNA repair after radiation, combined with radiation in patients with advanced non-small cell lung cancer (NSCLC). Between July 1995 and January 1997, 10 patients with NSCLC were registered. Thirty-six mg/m2/day etoposide was infused continuously for a mean of 19 days (range 14-26). Patients tolerated a mean total dose of accelerated hyperfractionated thoracic radiotherapy (1.5 Gy twice per day) of 52.6 Gy (range 33-60). The primary tumors of 7 patients showed partial responses and distant metastasis progression occurred before primary tumor progression in all 7 responders. The hematological adverse effects of chemoradiotherapy were grade 3 or 4 leukopenia in all 10 patients, grade 3 anemia developed in 3, and 2 had grade 3 thrombocytopenia. Six patients contracted infections and one of them died of pneumonia. The major non-hematological adverse effect was esophagitis, which was grade 3 in 3 patients, one of whom died of renal dysfunction. The serum etoposide concentrations were 1.6-2.0 microgram/ml, except in one patient, who had liver dysfunction due to B-type hepatitis. DNA repair gene XRCC1 mRNA expression in peripheral blood mononuclear cells was analyzed, using the reverse transcriptase-polymerase chain reaction, in 8 patients and was suppressed during etoposide infusion in 2. No relationship was observed between serum etoposide concentration and XRCC1 expression and clinical outcome. In conclusion, continuous etoposide infusion combined with thoracic radiation induces severe toxicity and should be given only after careful consideration.

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