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 correlation with tumor response and patient survival, we undertook the present study in 20 small cell lung cancer (SCLC) patients. All patients underwent the same treatment based on CT courses of carboplatin and etoposide. Blood samples were taken before and immediately after CT and every 12 weeks during follow-up. Nuclear DNA damage was determined through the variations in three mitochondrial pseudogene mutations in DNA of peripheral blood mononuclear cells. They were detected by mutation-specific PCR and assessed by a semiquantitative method. The relative level of mutation rose after chemotherapy in all cases. Among the 11 patients (55%) with higher relative levels of mutations, 9 (82%) of them achieved a complete response. In contrast, of the 9 patients (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 18 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 chemotherapy treatment correlates positively with tumor response and patient survival.
Silva
J M
JM
Department of Medical Oncology, Clinica Puerta de Hierro, Madrid, Spain.
Garcia
J M
JM
Dominguez
G
G
Silva
J
J
Rodriguez
R
R
Portero
J L
JL
Corbacho
C
C
Provencio
M
M
España
P
P
Bonilla
F
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D016190:Carboplatin / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000235:genetics*; D004249:DNA Damage; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011544:Pseudogenes
D017931:DNA Primers; D004273:DNA, Neoplasm; D005047:Etoposide; D016190:Carboplatin