Chronotherapy of colorectal cancer
Chronotherapy of colorectal cancer
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DOI：
10.1081/cbi-120002602
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发表时间：
2002-01-01
影响因子：
2.8
通讯作者：
Giacchetti, S
中科院分区：
文献类型：
--
作者：
Giacchetti, S
时间疗法包括根据昼夜节律进行化疗。这些基于遗传的节律调节正常组织中的细胞代谢和细胞增殖。因此，与其他30种抗癌药物一样，5-氟尿嘧啶（5-FU）和奥沙利铂（L-OHP）的宿主耐受性和抗肿瘤疗效在实验室啮齿动物中的给药时间差异很大。将这一概念转移到临床的主要目的是通过调节药物递送至宿主耐受性的24小时节律来增加治疗的剂量强度。一种特定的技术（可编程的时间输液泵），使管理的时间治疗完全走动的患者。I-II期临床试验显示，时间疗法显著增加了转移性结直肠癌患者对高剂量抗癌药物的耐受性，并提高了抗肿瘤活性。这些安全的药物递送条件导致首次证明了5-FU-亚叶酸-L-OHP方案的高活性。这三种药物的时间疗法也允许手术切除以前不能切除的肝和肺转移瘤。这种新的内科-外科治疗方法为不可切除的结直肠癌转移患者的转移性疾病的治愈提供了希望。版权所有（C）2002 Marcel Dekker，Inc.
Chronotherapy consists of chemotherapy delivery according to circadian rhythms. These genetically based rhythms modulate cellular metabolism and cell proliferation in normal tissues. As a result, both the host tolerance and antitumor efficacy of 5-fluorouracil (5-FU) and oxaliplatin (L-OHP), like 30 other anticancer drugs, vary largely according to the dosing time in laboratory rodents. The transfer of this concept to the clinic is aimed primarily at increasing the dose-intensity of the therapy through adjustment of drug-delivery to 24h rhythms in host tolerance. A specific technology (programmable-in-time infusion pumps) enables administration of chronotherapy to fully ambulatory patients. Phase I-II clinical trials show chronotherapy significantly increases tolerance to high doses of cancer drugs and improves antitumor activity in patients with metastatic colorectal cancer. These safe conditions of drug-delivery led to the first demonstration of the high activity of the 5-FU-Ieucovorin-L-OHP protocol. Chronotherapy with these three drugs also allows surgical removal of previously unresectable liver and lung metastases. This novel medico-surgical management provides hope for the cure of metastatic disease in patients with unresectable colorectal cancer metastases. Copyright (C) 2002 by Marcel Dekker, Inc.