DNA damage after chemotherapy correlates with tumor response and survival in small cell lung cancer patients

To explore the induction of chemotherapy (CT) DNA damage and its correlatio n with tumor response and patient survival, we undertook the present study in 20 small cell lung cancer (SCLC) patients. All patients underwent the sa me treatment based on CT courses of carboplatin and etoposide. Blood sample s were taken before and immediately after CT and every 12 weeks during foll ow-up. Nuclear DNA damage was determined through the variations in three mi tochondrial pseudogene mutations in DNA of peripheral blood mononuclear cel ls. They were detected by mutation-specific PCR and assessed by a semiquant itative method. The relative level of mutation rose after chemotherapy in a ll cases. Among the 11 patients (55%) with higher relative levels of mutati ons, 9 (82%) of them achieved a complete response. In contrast, of the 9 pa tients (45%) with lower relative levels of mutations, only 2 (18%) achieved a complete response. displaying a statistically significant difference (P = 0.02). The overall survival for patients with marked genomic damage was 1 8 months (range 10-24), and for patients with low degree of DNA damage, it was 12 months (range 5-15) (P = 0.002). Genomic damage detected after chemo therapy treatment correlates positively with tumor response and patient sur vival. (C) 2000 Elsevier Science B.V. All rights reserved.