A feasibility study of continuous etoposide infusion combined with thoracic radiation for non-small cell lung cancer

We conducted a feasibility study of continuous etoposide infusion, which wa s 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 m g/m(2)/day etoposide was infused continuously for a mean of 19 days (range 14-26). Patients tolerated a mean total dose of accelerated hyperfractionat ed thoracic radiotherapy (1.5 Gy twice per day) of 52.6 Gy (ran,ae 33-60). The primary tumors of 7 patients showed partial responses and distant metas tasis progression occurred before primary tumor progression in all 7 respon ders. The hematological adverse effects of chemoradiotherapy were grade 3 o r 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 th em died of pneumonia. The major nonhematological adverse effect was esophag itis, which was grade 3 in 3 patients, one of whom died of renal dysfunctio n. The serum etoposide concentrations were 1.6-2.0 mu g/ml, except in one p atient, who had liver dysfunction due to B-type hepatitis. DNA repair gene XRCC1 mRNA expression in peripheral blood mononuclear cells was analyzed, u sing the reverse transcriptase-polymerase chain reaction, in 8 patients and was suppressed during etoposide infusion in 2. No relationship was observe d between serum etoposide concentration and XRCC1 expression and clinical o utcome. In conclusion, continuous etoposide infusion combined with thoracic radiation induces severe toxicity and should be gives only after careful c onsideration.