Angiogenesis and the efficacy of postoperative administration of UFT in pathologic stage I non-small cell lung cancer.
UFT is an oral 5-fluorouracil derivative drug that may improve postoperative survival in non-small cell lung cancer (NSCLC), and experimental studies have shown that UFT inhibits tumor angiogenesis. In the present study, therefore, the correlation between tumor angiogenesis (intratumoral microvessel density, IMVD) and the efficacy of UFT in 162 patients with pathologic stage I NSCLC was examined. For higher IMVD tumors (IMVD > or = 20, n = 80), the 5-year survival rate of UFT-treated patients (82.5%) was significantly higher than that of surgery-alone patients (61.8%, P = 0.032). For lower IMVD tumors (n = 82), however, there was no difference in the survival between these groups (5-year survival rates, 84.9% and 82.6%, respectively; P = 0.657). Multivariate analyses confirmed that postoperative UFT administration was effective for higher IMVD tumors (P = 0.046; relative risk [RR] and the 95% confidence interval [CI], 0.288 [0.084-0.979]), but not for lower IMVD tumors (P = 0.616; 0.726 [0.208-2.539]). Moreover, vascular endothelial growth factor (VEGF) status was also a predictive factor. For tumor showing strong VEGF expression (n = 63), UFT administration improved the survival (5-year survival rates of UFT-treated patients and surgery-alone patients, 84.6% and 60.0%, respectively; P = 0.048); for weakly VEGF-expressing tumors (n = 99), UFT administration did not influence the survival (5-year survival rates, 83.4% and 79.1%, respectively; P = 0.455). Multivariate analyses demonstrated that UFT administration seemed to be effective for strong VEGF tumors (P = 0.063; RR and the 95% CI, 0.234 [0.051-10.81]), but not for weak VEGF tumors (P = 0.456; 0.673 [0.293-1.900]). In conclusion, the efficacy of postoperative UFT administration in NSCLC was correlated with tumor angiogenesis.
Tanaka
Fumihiro
F
Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. ftanaka@kuhp.kyoto-u.ac.jp
Yanagihara
Kazuhiro
K
Otake
Yosuke
Y
Miyahara
Ryo
R
Wada
Hiromi
H
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D015993:Life Tables; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011013:Pneumonectomy; D011184:Postoperative Period; D011355:Prodrugs / Q000008:administration & dosage / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D004338:Drug Combinations; D009363:Neoplasm Proteins; D011355:Prodrugs; C096910:UFT(R) drug; D042461:Vascular Endothelial Growth Factor A; D005641:Tegafur; D014498:Uracil