title: Prospective phase II trial of a combination of fixed dose rate infusion of gemcitabine with cisplatin and UFT as a first-line treatment in patients with advanced non-small-cell lung carcinoma.
abstract: OBJECTIVE
  The standard chemotherapy for non-elderly patients with advanced non-small-cell lung cancer (NSCLC) is platinum-based doublet combination therapy. Preclinical and clinical evidence indicates that infusion at the fixed dose rate (FDR) of 10mg/(m(2)min) may be more effective than a standard 30-min infusion of gemcitabine. In addition, oral uracil-tegafur (UFT) was associated with a survival advantage in the adjuvant setting. Therefore, we performed a phase II study using the combination of gemcitabine, cisplatin and UFT as first-line therapy in patients with advanced NSCLC.
  
  
  METHODS
  Eligible patients had histologically or cytologically confirmed stage IIIB or IV NSCLC with a performance status of 0-2 and were chemotherapy-naive. Gemcitabine (1,250 mg/m(2), 10mg/(m(2)min) on days 1 and 8, respectively) and cisplatin (75 mg/m(2) on day 1) were injected intravenously and UFT (400mg/day) was administered orally on days 1-14. Treatment was repeated every 3 weeks for up to six cycles. Primary endpoint was overall response rate and secondary endpoints were overall survival, time to progression and safety profile.
  
  
  RESULTS
  Thirty-seven patients were enrolled. The median age was 60 years (range: 44-72 years). The performance status was 0 in 4, 1 in 30, and 2 in 3 patients. Twenty-three patients completed six cycles. Complete response was achieved in one (3%) patient, partial response in 17 (46%) patients, and stable disease in 10 (27%) patients. The overall response rate was 48.6% on an intention-to-treat basis and 54.5% of patients in whom a response evaluation was possible (n=33). The median survival time was 14.7 months (95% confidence interval [CI] 11.2-18.2), the 1-year survival rate was 54% and the median time to progression was 5.4 months (95% CI 4.3-6.4). Toxicities were moderate and mostly hematological adverse events. Grade 3/4 neutropenia occurred in 37% of patients and four patients experienced febrile neutropenia. Grade 3/4 anemia and thrombocytopenia occurred in 19% and 5% of patients, respectively. Non-hematological toxicities were mild.
  
  
  CONCLUSIONS
  The combination of gemcitabine, cisplatin and UFT is an active and well-tolerated first-line regimen in patients with advanced NSCLC.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714, Republic of Korea.
authors.forename: Hawk
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714, Republic of Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Baek
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Jong-Joon
authors.initials: JJ
authors.lastname: Ahn
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Yangjin
authors.initials: Y
authors.lastname: Jegal
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Kwang Won
authors.initials: KW
authors.lastname: Seo
authors.affiliation: Department of Thoracic and Cardiovascular surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Chang Ryul
authors.initials: CR
authors.lastname: Park
authors.affiliation: Department of Thoracic and Cardiovascular surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Je Kyoun
authors.initials: JK
authors.lastname: Shin
authors.affiliation: Department of Thoracic and Cardiovascular surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Jong Pil
authors.initials: JP
authors.lastname: Jung
authors.affiliation: Department of Thoracic and Cardiovascular surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Woon Jung
authors.initials: WJ
authors.lastname: Kwon
authors.affiliation: Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Ae Kyung
authors.initials: AK
authors.lastname: Jeong
authors.affiliation: Department of Radiation Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Noh
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714, Republic of Korea.
authors.forename: Jae-Hoo
authors.initials: JH
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714, Republic of Korea. Electronic address: yjmin@uuh.ulsan.kr.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Min
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D005641:Tegafur; D014498:Uracil; D002945:Cisplatin; D000093542:Gemcitabine