Cheng A L, Yeh K H, Lin J T, Hsu C, Liu M Y
Department of Internal Medicine, National Taiwan University Hospital, Taipei.
Anticancer Res. 1998 Mar-Apr;18(2B):1267-72.
We have previously shown that weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin (HDFL), a regimen initially designed for the treatment of advanced colorectal cancer, is also effective in the treatment of gastric cancer. This HDFL regimen is unique in that it is virtually non-myelosuppressive, and thus provides a comerstone on which ideal protocols may be developed. In this prospective phase II study, we examined the efficacy and toxicity of PE (cisplatin, etoposide)-HDFL, a HDFL-based combination chemotherapy, in the treatment of advanced-gastric cancer. This regimen consisted of cisplatin 60 mg/m2, i.v., D1; etoposide 65 mg/m2, i.v., D1-3; and 5-fluorouracil 2600 mg/m2 plus leucovorin 300 mg/m2, 24-hour i.v. infusion by an ambulatory infusion pump, D2,9,16; repeated every 4 weeks. The major eligibility criteria of the patients included: a) a histologically confirmed, objectively measurable, recurrent or primary inoperable gastric adenocarcinoma; b) age > or = 75 years; c) a Karnofsky performance status > or = 50%; d) an absolute granulocyte count (AGC) > or = 2000/mm3, and a platelet count > or = 100,000/mm3; e) a serum bilirubin concentration < or = 2.0 mg/dl; f) a serum creatinine concentration < or = 1.5 mg/dl; and g) a signed informed consent. Between March 1992 and June 1996, a total of 42 patients were enrolled onto the study. There were 31 men and 11 women with a median age of 54 (24-75) years; these included 16 primary metastatic, 3 locally advanced and inoperable, and 23 postgastrectomy recurrent gastric cancer patients. ECOG (Eastern Cooperative Oncology Group) grade III/IV leukopenia and thrombocytopenia developed in 34.0% and 11.0% of a total of 229 courses given, respectively. There was no treatment-related death. Four patients developed a reversible neurotoxicity; and two of them refused further chemotherapy. Among the 40 patients evaluable for responses, 9 [22.5%; 12-38%, 95% confidence interval (C.I.)] patients achieved complete remission, and 20 [50.0%; 33-67%, 95% C.I.] patients achieved partial remission. The overall response rate was 72.5% [56-86%, 95% C.I.]. The overall median survival and median time to progression of the responders were 10 and 7 months, respectively. The overall median survival of the whole group was 9 months. We concluded that PE-HDFL is a highly effective treatment for advanced gastric cancer. The treatment-related toxicity was mild and the patients' compliance was satisfactory.
我们之前已经表明，每周24小时输注高剂量5-氟尿嘧啶和亚叶酸钙（HDFL），这种最初设计用于治疗晚期结直肠癌的方案，在治疗胃癌方面也有效。这种HDFL方案的独特之处在于它几乎没有骨髓抑制作用，因此为开发理想的方案提供了基石。在这项前瞻性II期研究中，我们研究了基于HDFL的联合化疗方案PE（顺铂、依托泊苷）-HDFL治疗晚期胃癌的疗效和毒性。该方案包括顺铂60mg/m²，静脉滴注，第1天；依托泊苷65mg/m²，静脉滴注，第1 - 3天；以及5-氟尿嘧啶2600mg/m²加亚叶酸钙300mg/m²，通过便携式输液泵进行24小时静脉输注，第2、9、16天；每4周重复一次。患者的主要入选标准包括：a）经组织学证实、客观可测量的复发性或原发性不可切除胃腺癌；b）年龄≥75岁；c）卡诺夫斯基体能状态≥50%；d）绝对粒细胞计数（AGC）≥2000/mm³，血小板计数≥100,000/mm³；e）血清胆红素浓度≤2.0mg/dl；f）血清肌酐浓度≤1.5mg/dl；g）签署知情同意书。1992年3月至1996年6月，共有42例患者纳入该研究。其中男性31例，女性11例，中位年龄54（24 - 75）岁；包括16例原发性转移、3例局部晚期且不可切除以及23例胃切除术后复发性胃癌患者。在总共229个疗程中，分别有34.0%和11.0%的患者出现了东部肿瘤协作组（ECOG）III/IV级白细胞减少和血小板减少。没有与治疗相关的死亡。4例患者出现了可逆性神经毒性；其中2例拒绝进一步化疗。在40例可评估疗效的患者中，9例[22.5%；12 - 38%，95%置信区间（C.I.）]患者达到完全缓解，20例[50.0%；33 - 67%，95% C.I.]患者达到部分缓解。总缓解率为72.5%[56 - 86%，95% C.I.]。缓解患者的总中位生存期和中位疾病进展时间分别为10个月和7个月。整个组的总中位生存期为9个月。我们得出结论，PE - HDFL是治疗晚期胃癌的一种高效疗法。治疗相关毒性较轻，患者依从性良好。
