Alternate-day oral therapy with TS-1 for advanced gastric cancer
Alternate-day oral therapy with TS-1 for advanced gastric cancer
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TS-1 隔日口服疗法治疗晚期胃癌
DOI：
10.1007/s10147-004-0381-9
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发表时间：
2004
影响因子：
3.3
通讯作者：
T. Shirasaka
中科院分区：
文献类型：
--
作者：
W. Arai;Y. Hosoya;M. Hyodo;Taku Yokoyama;Y. Hirashima;Y. Yasuda;H. Nagai;T. Shirasaka
研究背景TS-1(1 M替加氟-0.4 M 5-氯-2，4-二羟基嘧啶-1- M氧酸钾)对胃癌的单药有效率高达40%以上，但推荐的4周给药间歇2周停药方案往往会产生不良反应。交替剂量的嘧啶氟化物抗癌药物可以在不影响其疗效的情况下减少其不良反应。我们尝试了TS-1的隔日治疗，目的是避免不良反应，并显著延长给药时间。方法观察隔日剂量TS-1的临床疗效和不良反应，并测定血5-氟尿嘧啶(5-FU)浓度。临床疗效评价依据实体瘤治疗反应新指南(RECIST)，不良反应评价依据美国国家癌症研究所NCI共同毒性标准(CTC)。结果在92例患者中，72例(78%)TS-1方案因不良反应改用隔日剂量。由于担心不良反应，20名患者从一开始就接受了隔日给药方案的治疗。隔日剂量在临床上是有效的，因为在相对根治切除的34例患者中，有28例仍然活着，没有复发。58例非根治性切除或不能切除或复发的癌症患者的中位生存期为332天。在这58例患者中，53%的患者在12周以上达到部分缓解和病情稳定。我们跟踪观察了36名接受隔日治疗的患者的血液5-FU水平随时间的变化，在这些患者中，TS-1在每隔一天之前每天服用一次。TS-1隔日给药的血药浓度谷值明显低于每日给药，且5-FU的血药浓度在隔日给药后2 h达到峰值。结论与每日给药相比，隔天给药可减少不良反应，同时保证有效血药浓度，并提供足够的临床疗效。
BackgroundTS-1 (1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyrimidine-1 M potassium oxonate) has a high single-agent response rate, of more than 40%, for gastric cancer; however, the recommended regimen of 4 weeks of administration interrupted by 2 weeks of drug withdrawal frequently causes adverse effects. The alternate-day dosage of pyrimidine fluoride anticancer drugs could reduce their adverse effects without compromising their effects. We attempted an alternate-day therapy with TS-1 aiming at the avoidance of adverse effects and significantly longer duration of administration.MethodsWe observed patients for clinical effects and adverse effects under alternate-day dosage of TS-1, and determined blood 5-fluorouracil (FU) levels. The judgment of clinical effects was based on the New Guidelines to Evaluate the Response to Treatment in Solid Tumors (RECIST), whereas the evaluation of adverse effects was based on the National Cancer Institute NCI-common toxicity criteria (CTC).ResultsIn 72 (78%) of 92 patients, the TS-1 regimen was converted to the alternate-day dosage because of adverse effects. Twenty patients were treated with the alternate-day dosage regimen from the start because of the fear of adverse effects. The alternate-day dosage was clinically effective, as 28 of 34 patients after relatively curative resection remained alive and free from recurrence. The median survival time of 58 patients after noncurative resection or with unresectable or recurrent cancer was 332 days. Fifty-three percent of these 58 patients achieved partial response and stable disease of more than 12 weeks’ duration. We followed time-dependent changes in blood 5-FU levels in 36 of the patients on alternate-day therapy, in whom TS-1 had been administered daily before being administered every other day. The trough level was significantly lower when TS-1 was administered on alternate days, and blood 5-FU reached a peak at sufficiently effective levels at 2 h even after administration on the alternate-day basis.ConclusionThis study demonstrated that, compared with daily administration, alternate-day administration of TS-1 reduces adverse effects, and simultaneously ensures effective blood levels and provides sufficient clinical effects.