[Interferon-alpha in adjuvant treatment of colorectal carcinoma].

L Staib, K H Link, D Henne-Bruns
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引用次数: 0

Abstract

Unlabelled: Based on preclinical and clinical studies, in this German three-arm adjuvant multicenter trial the FOGT (Forschungsgruppe Onkologie Gastrointestinale Tumoren) studied whether one of the 5-FU modulations with either folinic acid(FA) or Interferon alpha-2a (IFNa) is superior to the recommended standard of adjuvant treatment in R0-resected colon cancer, 5-fluorouracil (5-FU) plus levamisole (LEV) for 12 months, in terms of overall survival rates.

Patients/methods: From 7/92 to 10/99 813 patients with resected colon cancer stage II (only T4N0M0, 63 pts.) and stage III (750 pts.) were randomized into three treatment groups and stratified according to N-stage and participating centers (64 hospitals). The patients received a postoperative loading course with 5-FU [450 mg/m2 d1-5 (arms A and C)] or 5-FU [450 mg/m2 plus folinic acid (Rescuvolin, medac, Hamburg, Germany), 200 mg/m2 d1-5 (arm B)]. After completion of the first chemotherapy cycle LEV was administered orally at 150 mg/d d1-3, every 2 weeks. After a 4-week chemotherapy-free interval the treatment was continued weekly for up to 52 weeks. The standard group, arm A (279 pts.) was treated with 5-FU i.v. (450 mg/m2 at d 1, q 1 w) plus LEV. 5-FU plus LEV was modulated in arm B (283 pts.) with FA (200 mg/m2 d1, q 1 w), and in arm C (251 pts.) with IFNa at 6 million units 3x/week, q 1 w. Chemotherapy doses were adjusted to toxicity if toxic events > WHO 2 occurred. The patients were followed-up to determine relapse rates and--patterns and survival. Survival rates were calculated according to Kaplan-Meier, and treatment costs and immune effects were analysed.

Results: Toxic event(s) > WHO2, mainly leukopenia, diarrhea and nausea, occurred in 113 pts. (14%), in arms A (8%), B (13%) and C (32%). Discontinuance rates were 28% (all), 29% (A), 21% (B), 34% (C), but 80% of patients received > or = 6 months treatment. Overall relapse rates were 27% (all), 30% (A), 24% (B) and 28% (C). Tumors relapsed either locally (2% each) or distant (A: 22%, B: 20%, C: 22%). 4-year overall survival rates in arms A, B and C were 66%, 77%, 66%, respectively. The 4-year survival rate in arm B was significantly superior to arms A and C (p < 0.02, log-rank). There were no signs of a superior immune function in either treatment arm (skin test, proliferation, cytotoxicity, flow cytometry). Treatment costs per patient were 2,500 [symbol: see text](arm A), 3,500 [symbol: see text](arm B) or 10,850 [symbol: see text](arm C), respectively.

Conclusion: Adjuvant therapy with 5-FU plus FA plus LEV for 12 months is superior to the recommended standard (5-FU + LEV, 12 m). IFNa-modulation of 5-FU (plus LEV) adds toxicity and high treatment costs without therapeutic benefit.

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[干扰素在大肠癌辅助治疗中的应用]。
未标记:基于临床前和临床研究,FOGT (Forschungsgruppe Onkologie gastro胃肠道肿瘤)在这项德国三组辅助多中心试验中研究了叶酸(FA)或干扰素α -2a (IFNa)的5-FU调节是否优于r0切除结肠癌辅助治疗的推荐标准,即5-氟尿嘧啶(5-FU)加左咪唑(LEV)治疗12个月的总生存率。患者/方法:从7月92日至10月99日,813例切除的结肠癌II期(仅T4N0M0, 63例)和III期(750例)患者随机分为三个治疗组,并根据n期和参与中心(64家医院)进行分层。患者接受5-FU [450 mg/m2 d1-5 (a组和C组)]或5-FU [450 mg/m2 +亚叶酸(Rescuvolin, medac, Hamburg, Germany), 200 mg/m2 d1-5 (B组)]的术后负荷疗程。第一个化疗周期结束后,每2周口服150 mg/d d1-3给药LEV。在4周的无化疗间隔后,每周继续治疗至52周。标准组,A组(279名患者)给予5-FU静脉注射(450 mg/m2,第1天,第1周)加LEV。5-FU加LEV在B组(283例)用FA (200 mg/m2, d1, q 1 w)调节,在C组(251例)用IFNa(600万单位,3次/周,q 1 w)调节。如果毒性事件> WHO 2发生,化疗剂量调整为毒性。对患者进行随访,以确定复发率、模式和生存率。根据Kaplan-Meier法计算生存率,并分析治疗费用和免疫效果。结果:113例患者发生WHO2以上毒性事件,主要为白细胞减少、腹泻和恶心。(14%), A (8%), B(13%)和C(32%)。停药率分别为28%(全部)、29% (A)、21% (B)、34% (C),但80%的患者接受了>或= 6个月的治疗。总体复发率为27%(全部),30% (A), 24% (B)和28% (C)。肿瘤局部复发(各2%)或远处复发(A: 22%, B: 20%, C: 22%)。A、B、C组4年总生存率分别为66%、77%、66%。B组4年生存率显著优于A组和C组(p < 0.02, log-rank)。在两个治疗组(皮肤试验、增殖、细胞毒性、流式细胞术)均未发现免疫功能优越的迹象。每位患者的治疗费用分别为2,500[符号:见文](A组),3,500[符号:见文](B组)或10,850[符号:见文](C组)。结论:5-FU + FA + LEV辅助治疗12个月优于推荐标准(5-FU + LEV, 12 m), ifna调节5-FU (+ LEV)增加毒性,治疗费用高,无治疗效果。
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[120th Congress of the German Surgical Society. 29 April-2 May 2003, Munich, Germany. Abstracts]. [Clinical application--suture materials]. [Inguinal hernia: TAPP--future standard?]. [Preservation of the recurrent laryngeal nerve]. [Surgery of euthyroid nodular goiter: special considerations in surgery of recurrent struma].
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