Mani S, Schiano T, Garcia J C, Ansari R H, Samuels B, Sciortino D F, Tembe S, Shulman K L, Baker A, Benner S E, Vokes E E
Section of Hematology/Oncology, Cancer Research Center, Chicago, IL, USA.
Invest New Drugs. 1998;16(3):279-83. doi: 10.1023/a:1006104217137.
Although UFT 300 mg/m2/day and leucovorin 90 mg/day administered orally in divided doses administered every 8 hours for 28 days repeated every 35 days could be administered safely to patients with advanced hepatomas and good performance status, this combination and schedule has limited activity in treating advanced hepatoma.
BACKGROUND/PURPOSE: Biochemical modulation of 5-fluorouracil has yielded higher response rates in hepatoma when compared to treatment with 5-fluorouracil as a single agent, although the impact on survival has been negligible. This study was conducted to determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) plus oral calcium leucovorin in the treatment of patients with advanced hepatocellular carcinoma (hepatoma).
Sixteen patients with advanced measurable hepatocellular carcinoma were enrolled onto the trial. All patients had a Karnofski performance status > or = 60%, platelet count > or = 75,000/micro L, total bilirubin < or = 2.0 x institutional upper limit of normal but otherwise normal liver and kidney function profile and bidimensionally measurable disease by CT or ultrasound examination. None of these patients received prior cytotoxic chemotherapy or radiation therapy for advanced disease. Fourteen patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days repeated every 35 days. Two patients registered for the trial but did not receive study medication. Objective tumor response, the primary purpose of this trial, was evaluated after two courses of therapy. Other end-points included toxicity, time to progression, and overall survival.
Fourteen patients were evaluable for response and toxicity, respectively. No complete or partial responders were observed in this trial. Three patients had stable disease lasting 17 to 22 weeks. Toxicity was mild with severe (grade 3 or 4) liver pain, diarrhea, anorexia/nausea, fatigue, dyspnea, hyperbilirubinemia, anemia, and edema seen in 3 (21%), 2 (14%), 3 (21%), 2 (14%), 1 (7%), 1 (7%), 1 (7%) and 1 (7%) patients, respectively. The most frequent grade I and 2 toxic effects included fever of unknown origin, dyspnea, nausea, vomiting and diarrhea.
UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate antitumor activity against advanced hepatomas. Further treatment using this regimen is not recommended for this disease.
尽管对于晚期肝癌且身体状况良好的患者，可以安全地给予氟尿嘧啶替加氟300mg/m²/天和亚叶酸90mg/天，口服，分剂量，每8小时一次，共28天，每35天重复一次，但这种联合用药方案在治疗晚期肝癌方面的活性有限。
背景/目的：与单独使用5-氟尿嘧啶治疗相比，5-氟尿嘧啶的生化调节在肝癌治疗中产生了更高的缓解率，尽管对生存率的影响可以忽略不计。本研究旨在确定4:1摩尔浓度比的尿嘧啶和替加氟（UFT；百时美施贵宝公司，康涅狄格州沃灵福德）联合口服亚叶酸钙治疗晚期肝细胞癌（肝癌）患者的活性并评估其毒性。
16例晚期可测量肝细胞癌患者入组该试验。所有患者的卡氏评分≥60%，血小板计数≥75,000/μL，总胆红素≤2.0×机构正常上限，肝功能和肾功能其他方面正常，且通过CT或超声检查可进行二维测量。这些患者均未接受过针对晚期疾病的先前细胞毒性化疗或放疗。14例患者接受300mg/m²/天的UFT加90mg/天的亚叶酸钙，口服，分每日剂量，每8小时一次，共28天，每35天重复一次。2例患者登记参加试验但未接受研究药物治疗。在两个疗程治疗后评估本试验的主要目的——客观肿瘤反应。其他终点包括毒性、疾病进展时间和总生存期。
分别有14例患者可评估反应和毒性。本试验中未观察到完全缓解或部分缓解者。3例患者疾病稳定，持续17至22周。毒性较轻，分别有3例（21%）、2例（14%）、3例（21%）、2例（14%）、1例（7%）、1例（7%）、1例（7%）和1例（7%）患者出现严重（3级或4级）肝痛、腹泻、厌食/恶心、疲劳、呼吸困难、高胆红素血症、贫血和水肿。最常见的1级和2级毒性反应包括不明原因发热、呼吸困难、恶心、呕吐和腹泻。
300mg/m²/天的UFT加90mg/天的口服亚叶酸钙治疗28天未显示出对晚期肝癌的抗肿瘤活性。不推荐使用该方案进一步治疗这种疾病。
