Abstract

Many anti-cancer drugs induce formation of lipid peroxidation products that are toxic for lung cancer cells in vitro. We tested whether changes of serum thiobarbituric acid reactive substances (TBARs) and Schiff's bases (SB) are associated with treatment efficacy in 37 small cell lung cancer (SCLC) patients. Subjects received carboplatin (350 mg/m2, i.v.-Day 1), vincristine (1.3 mg/m2, i.v.-Day 1), and etoposide (120 mg/m2, oral dose-Days 1-4). Then 5 subsequent cycles were repeated at 21-day intervals. Serum TBARs and SB were measured fluorimetrically before and 6, 24h after introduction of the 1st, 3rd and 6th cycles. TBARs and SB levels rose 24 h after 1st chemotherapy in the whole group (2.5+/-1.4 vs. 4.2+/-2.0 micromol/dl, P<0.001 and 26.3+/-16.7 vs. 29.7+/-9.8U(430)/ml, P<0.01, respectively) and the highest increments were in 19 patients with complete or partial response after 1st, 3rd and 6th cycles. In 9 subjects with progressive disease occurring before the 2nd cycle (early progression) TBARs and SB decreased 6 and 24h after the 1st cycle (4.3+/-1.2 vs. 3.4+/-1.4, P<0.05 vs. 2.7+/-0.9 micromol/dl, P<0.05 and 50.2+/-17.0 vs. 36.7+/-13.2, P<0.05 vs. 36.5+/-13.4 U(430)/ml, P<0.01, respectively). Patients survival correlated with the 1st cycle-induced TBARs (r=0.49, P<0.001) and SB (r=0.56, P<0.002) increments. Subjects with negative SB and TBARs increments (n=8) had shorter survival than those (n=29) with positive increments in lipid peroxidation products (log rank test P<0.005). Monitoring of circulatory TBARs and SB may be helpful for screening of SCLC patients with high risk of early disease progression and chemotherapy failure.

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