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

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2008-04, Vol.60 (1), p.83-91
• Main Authors: Shin, Su Jin, Kim, Hawk, Baek, Jin Ho, Ahn, Jong-Joon, Jegal, Yangjin, Seo, Kwang Won, Park, Chang Ryul, Shin, Je Kyoun, Jung, Jong Pil, Kim, Jeong Won, Cha, Hee Jeong, Kwon, Woon Jung, Jeong, Ae Kyung, Noh, Young Ju, Park, Jae-Hoo, Min, Young Joo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Female; Fixed dose rate; Gemcitabine; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - drug therapy; Male; Medical sciences; Middle Aged; Non-small-cell lung cancer; Pneumology; Prospective Studies; Pulmonary/Respiratory; Tegafur - administration & dosage; Tumors; Tumors of the respiratory system and mediastinum; Uracil - administration & dosage; Uracil-tegafur
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2007.09.013

Summary Purpose 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 10 mg/(m2 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. Patients and 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 (1250 mg/m2 , 10 mg/(m2 min) on days 1 and 8, respectively) and cisplatin (75 mg/m2 on day 1) were injected intravenously and UFT (400 mg/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. Result 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. Conclusion The combination of gemcitabine, cisplatin and UFT is an active and well-tolerated first-line regimen in patients with advanced NSCLC.