Tsavaris N, Kosmas C, Gennatas K, Vadiaka M, Skopelitis E, Xila V, Rokana S, Margaris E, Zografos G, Papastratis G, Kouraklis G
Department of Pathophysiology, University of Athens, School of Medicine, Laikon General Hospital, Greece.
J Chemother. 2002 Aug;14(4):406-11. doi: 10.1179/joc.2002.14.4.406.
In the present study, we evaluated the efficacy and safety of the weekly combination of etoposide, leucovorin (LV) and 5-fluorouracil (5-FU) when administered as second-line chemotherapy in patients with relapsed/refractory advanced colorectal cancer (ACC), previously treated with weekly LV+5-FU. Etoposide was administered at 3 different dose levels (DLs), in 3 groups of 20 patients each (total: 60); DL-I: etoposide 80 mg/m2, DL-II: etoposide 120 mg/m2, and DL-III: etoposide 180 mg/m2, in 45 min i.v. infusion, and followed in all levels by LV 100 mg/m2 i.v. over 1 hour and 5-FU 500 mg/m2 i.v. bolus. Treatment was administered weekly until disease progression or unacceptable toxicity. No patients at DL-I responded, while 2 patients at DL-II and 3 at DL-III had a partial response (PR). Stable disease (SD) rates were as follows; at DL-I: 2, DL-II: 8 and DL-III: 9. More patients in DL-I progressed (n = 19) compared to DL-II (n=10) and DL-II (n = 8) (p < 0.0007). Time to progression was for DL-I, -II, -III: 17, 15, and 14 weeks, respectively. Median survival was DL-I, -II, -III: 30, 30, and 32.5 weeks, respectively. Toxicity consisted mainly of neutropenia, diarrhea and mucositis at all DLs, and was significantly more severe in DL-III. No difference was noted in responses between DL-II and DL-III. The authors conclude that the combination of etoposide with LV+5-FU has limited activity when administered after failure of weekly LV+5-FU in patients with ACC and should not be recommended for further evaluation.
在本研究中，我们评估了依托泊苷、亚叶酸钙（LV）和5-氟尿嘧啶（5-FU）每周联合方案作为二线化疗用于复发/难治性晚期结直肠癌（ACC）患者的疗效和安全性，这些患者此前接受过每周一次的LV + 5-FU治疗。依托泊苷以3种不同剂量水平（DLs）给药，每组20例患者，共3组（总计60例）；DL-I：依托泊苷80mg/m²，DL-II：依托泊苷120mg/m²，DL-III：依托泊苷180mg/m²，静脉输注45分钟，随后在所有剂量水平下，LV 100mg/m²静脉输注1小时，5-FU 500mg/m²静脉推注。每周进行治疗，直至疾病进展或出现不可接受的毒性。DL-I组无患者有反应，而DL-II组有2例患者、DL-III组有3例患者获得部分缓解（PR）。疾病稳定（SD）率如下：DL-I组为2例，DL-II组为8例，DL-III组为9例。与DL-II组（n = 10）和DL-III组（n = 8）相比，DL-I组更多患者出现疾病进展（n = 19）（p < 0.0007）。疾病进展时间方面，DL-I组、DL-II组、DL-III组分别为17周、15周和14周。中位生存期方面，DL-I组、DL-II组、DL-III组分别为30周、30周和32.5周。毒性主要包括所有剂量水平下的中性粒细胞减少、腹泻和黏膜炎，且DL-III组毒性明显更严重。DL-II组和DL-III组在反应方面未观察到差异。作者得出结论，对于ACC患者，在每周一次的LV + 5-FU治疗失败后给予依托泊苷联合LV + 5-FU方案的活性有限，不应推荐进一步评估。
