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.
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.
Shin
Su Jin
SJ
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.
Kim
Hawk
H
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.
Baek
Jin Ho
JH
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.
Ahn
Jong-Joon
JJ
Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Jegal
Yangjin
Y
Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Seo
Kwang Won
KW
Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Park
Chang Ryul
CR
Department of Thoracic and Cardiovascular surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Shin
Je Kyoun
JK
Department of Thoracic and Cardiovascular surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Jung
Jong Pil
JP
Department of Thoracic and Cardiovascular surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Kim
Jeong Won
JW
Department of Thoracic and Cardiovascular surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Cha
Hee Jeong
HJ
Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Kwon
Woon Jung
WJ
Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Jeong
Ae Kyung
AK
Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Noh
Young Ju
YJ
Department of Radiation Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Park
Jae-Hoo
JH
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.
Min
Young Joo
YJ
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.
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
D003841:Deoxycytidine; D005641:Tegafur; D014498:Uracil; D002945:Cisplatin; D000093542:Gemcitabine