title: Pretreatment fibrinogen levels are associated with response to chemotherapy in patients with small cell carcinoma of the lung: Department of Veterans Affairs Cooperative Study 188.
abstract: Small cell carcinoma of the lung (SCCL) responds commonly to combination chemotherapy but resistance to therapy follows. Prior reports have suggested that a relationship may exist between plasma fibrinogen levels and response to therapy in SCCL. This study was designed to determine the possible predictive value of the fibrinogen level for tumor response (chemoresistance) in SCCL. Pretreatment fibrinogen levels were correlated with outcome and response to therapy in a cohort of 119 previously untreated patients with SCCL who were admitted to VA Cooperative Study 188. Higher pretreatment fibrinogen levels at diagnosis correlated significantly with more advanced stage of disease at entry (P < 0.001) and with reduced overall survival (P = 0.030). In addition, higher pretreatment fibrinogen levels were correlated significantly with a reduced likelihood of achieving subsequent disease regression with combination chemotherapy (P = 0.005). Because several clinical trials have shown that anticoagulant therapy improves tumor response rates and survival of SCCL, we postulate that tumor cell thrombin generation not only promotes SCCL growth but may also be primarily responsible for both increased fibrinogen levels and for resistance to chemotherapy. These findings provide incentive for studies of thrombin effects on the development of multidrug resistance, and for new clinical trials of more potent and specific inhibitors of thrombin that may further improve tumor response and survival in SCCL.
authors.affiliation: Department of Veterans Affairs Medical & Regional Office Center, White River Junction, Vermont 05009-0001, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Meehan
authors.forename: L R
authors.initials: LR
authors.lastname: Zacharski
authors.forename: T E
authors.initials: TE
authors.lastname: Moritz
authors.forename: F R
authors.initials: FR
authors.lastname: Rickles
mesh_terms: D018288:Carcinoma, Small Cell / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D015331:Cohort Studies; D004351:Drug Resistance; D005340:Fibrinogen / Q000032:analysis*; D005341:Fibrinolysin / Q000032:analysis; D005344:Fibrinopeptide A / Q000032:analysis; D005345:Fibrinopeptide B / Q000032:analysis; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D009012:Mopidamol / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D013917:Thrombin / Q000032:analysis
chemical_list: D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D009012:Mopidamol; D005340:Fibrinogen; D013917:Thrombin; D005341:Fibrinolysin