Lutz M P, Königer M, Muche R, Ellenrieder V, Steinkamp M, Adler G, Gress T M
Abteilung Innere Medizin I, Universität Ulm.
Z Gastroenterol. 1999 Oct;37(10):993-7.
No single agent or combination chemotherapy protocol, with the exception of gemcitabine, has so far proven superior to standard bolus 5-fluorouracil regimes for the treatment of advanced pancreatic cancer. The present phase II trial was designed to study whether the effectivity of 5-fluorouracil can be improved with a weekly high-dose 5-fluorouracil schedule. 26 patients with cytologically or histologically verified, metastasized (n = 21) or locally advanced (n = 5) previously untreated adenocarcinoma of the pancreas were included in this study. Treatment consisted of weekly applications of 2,600 mg/m2 5-fluorouracil as 24-h infusion on days 1, 8, 15, 22, 29, 36. Treatment was repeated at day 50 and was continued until disease progression. Primary endpoints of the study were response rates and toxicity, secondary endpoints were survival and clinical benefit in terms of performance status, body weight and analgesia consumption. Toxicity of the regimen was mild with only four instances of grade-3 toxicity. Response rates were 8% (95% CI = 1.2-13.7) with two partial remissions. Improvement of at least one parameter of clinical benefit for > or = four weeks was observed for 11.5% of the study patients. The most prominent effect was a transient stabilization of objective tumor measurements (48% [95% CI = 27.8-68.7]) and individual parameters of clinical benefit (50-75%). Median survival was 248 days (95% CI = 164-459) for all patients included in the study. The present study indicates that the high-dose 5-fluorouracil regimen shows weak activity in advanced pancreatic cancer which seems comparable to gemcitabine.
除吉西他滨外，目前尚无单一药物或联合化疗方案被证明在治疗晚期胰腺癌方面优于标准推注5-氟尿嘧啶方案。本II期试验旨在研究每周高剂量5-氟尿嘧啶方案是否能提高5-氟尿嘧啶的疗效。本研究纳入了26例经细胞学或组织学证实的、转移性（n = 21）或局部晚期（n = 5）的未经治疗的胰腺腺癌患者。治疗方案为在第1、8、15、22、29、36天每周应用2600 mg/m² 5-氟尿嘧啶，持续24小时静脉输注。在第50天重复治疗，并持续至疾病进展。该研究的主要终点是缓解率和毒性，次要终点是生存率以及在体能状态、体重和镇痛药物消耗方面的临床获益。该方案的毒性较轻，仅有4例3级毒性反应。缓解率为8%（95% CI = 1.2 - 13.7），有2例部分缓解。11.5%的研究患者在至少一个临床获益参数上有≥4周的改善。最显著的效果是客观肿瘤测量值的短暂稳定（48% [95% CI = 27.8 - 68.7]）以及个体临床获益参数的稳定（50 - 75%）。纳入本研究所有患者的中位生存期为248天（95% CI = 164 - 459）。本研究表明，高剂量5-氟尿嘧啶方案在晚期胰腺癌中显示出较弱的活性，似乎与吉西他滨相当。
