Mani S, Kugler J W, Sciortino D F, Garcia J C, Ansari R H, Humerickhouse R, Michelassi F, Posner M C, Shulman K L, Schilsky R L, List M, Vokes E E, Benner S
Section of Hematology/Oncology, University of Chicago Pritzker School of Medicine, IL, USA.
Ann Oncol. 1998 Sep;9(9):1035-7. doi: 10.1023/A:1008427231049.
BACKGROUND/OBJECTIVES: Uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) has broad anti-tumor activity for cancers arising from the gastrointestinal tract. However, there are no published data regarding the efficacy of leucovorin-modulated UFT in patients with pancreatic cancer. The objective of this trial was to determine the activity and evaluate the toxicity of UFT plus oral calcium leucovorin in patients with advanced pancreatic adenocarcinoma.
Fourteen patients with advanced measurable adenocarcinoma of the pancreas were enrolled onto the trial. Patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided doses every eight hours for 28 days repeated every 35 days. Objective tumor response was evaluated after two courses of therapy.
Fourteen patients were evaluable for response and toxicity. No objective responses were seen. The median (range) time to progression and survival were 14 (1.6-37), and 15 (1.9-62) weeks, respectively. Toxicity was mild with severe (grade 3 or 4) hyperbilirubinemia, pain, diarrhea, transaminitis, venous thrombus, weakness, renal failure, confusion, and edema/ascites seen in three (21%), one (7%), two (14%), one (7%), one (7%), one (7%), one (7%), one (7%), and two (14%) patients, respectively.
In the 14 patients evaluable, UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate anti-tumor activity against advanced pancreatic adenocarcinoma; however, this oral regimen was well tolerated and devoid of neutropenia, significant oral mucositis or diarrhea.
背景/目的：尿嘧啶与替加氟按4:1摩尔浓度比组成的复方制剂（优福定；百时美施贵宝公司，美国康涅狄格州沃灵福德）对胃肠道癌症具有广泛的抗肿瘤活性。然而，关于亚叶酸钙调节的优福定在胰腺癌患者中的疗效尚无公开数据。本试验的目的是确定优福定联合口服亚叶酸钙对晚期胰腺腺癌患者的活性并评估其毒性。
14例晚期可测量胰腺腺癌患者入组本试验。患者接受300mg/m²/d的优福定加90mg/d的亚叶酸钙，分剂量每8小时口服一次，共28天，每35天重复一次。两个疗程治疗后评估客观肿瘤反应。
14例患者可评估反应和毒性。未观察到客观反应。进展时间和生存时间的中位数（范围）分别为14（1.6 - 37）周和15（1.9 - 62）周。毒性较轻，分别有3例（21%）、1例（7%）、2例（14%）、1例（7%）、1例（7%）、1例（7%）、1例（7%）、1例（7%）和2例（14%）患者出现严重（3或4级）高胆红素血症、疼痛、腹泻、转氨酶升高、静脉血栓、虚弱、肾衰竭、意识障碍和水肿/腹水。
在可评估的14例患者中，300mg/m²/d的优福定加90mg/d的口服亚叶酸钙治疗28天对晚期胰腺腺癌未显示出抗肿瘤活性；然而，这种口服方案耐受性良好，且无中性粒细胞减少、严重口腔黏膜炎或腹泻。
