Oxidative stress in non-small cell lung cancer patients after chemotherapy: association with treatment response

Abstract

Levels of lipid peroxidation, nitric oxide and glutathione, as well as superoxide dismutase activity were evaluated in non-small cell lung cancer patients before and after chemotherapy. Oxidative stress was shown to influence treatment efficacy and survival of these patients.

Background and objective: The aim of this study was to assess the level of oxidative stress after chemotherapy in non-small cell lung cancer patients, and its association with treatment response and survival.

Methods: Two hundred and three previously untreated non-small cell lung cancer patients and 150 healthy subjects were selected for the study. Patients received cisplatin+etoposide, and were followed for up to six cycles, for evaluation of oxidative stress. Blood levels of lipid peroxidation products (LPO), glutathione (GSH) and nitric oxide (NO), and superoxide dismutase (SOD) activity were measured at day 0 and after the third and sixth cycles of chemotherapy. Response and survival were measured at the end of follow up. Survival was estimated by the Kaplan-Meier method using the log-rank test.

Results: In the patients, pretreatment levels of LPO and NO were low, while GSH and SOD levels were high compared with those after the third and sixth cycles of chemotherapy. Among the 203 patients, there were 51 deaths, 82 non-responders and 70 responders at the end of the sixth cycle. Overall mean survival was higher among responders than non-responders (24.6 vs 21.2 weeks, P<0.01). The hazard ratio was 2.4 (95% CI: 1.3-3.77). Pretreatment levels of oxidative stress were similar among responders and non-responders (P>0.05). After the third and sixth cycles of chemotherapy, LPO and NO levels were low (P<0.05 or P<0.01) and GSH levels and SOD activity were high (P<0.05 or P<0.01) in responders as compared with non-responders.

Conclusions: In lung cancer patients, oxidative stress increased and anti-oxidant enzymes decreased as the disease progressed. Chemotherapy may suppress oxidative stress and decreased anti-oxidant enzyme activity in responders as compared with non-responders. These effects may contribute to improved survival among responders.