Circadian chemotherapy for gynecological and genitourinary cancers
Circadian chemotherapy for gynecological and genitourinary cancers
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DOI：
10.1081/cbi-120002600
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发表时间：
2002-01-01
影响因子：
2.8
通讯作者：
Hrushesky, WJM
中科院分区：
文献类型：
--
作者：
Kobayashi, M;Wood, PA;Hrushesky, WJM
手术、抗癌药物、放射治疗和生物制剂的昼夜节律时间可以改善毒性特征、肿瘤控制和宿主存活。多柔比星或吡拉西坦（06：00 h）和顺铂（18：00 h）的最佳时间癌症化疗增强了对晚期卵巢癌的控制，同时最大限度地减少了副作用，并增加了转移性子宫内膜癌的缓解率。采用相同的昼夜节律方法使阿霉素-顺铂治疗转移性膀胱癌的耐受性更好，客观缓解率为57%。这种最佳时机的治疗在辅助治疗中也是有效的，降低了局部晚期膀胱癌转移的预期频率。昼夜节律氟脱氧尿苷（FUDR）连续输注（15：00至21：00之间给予日剂量的70%）已被证明对转移性肾细胞癌有效，在大多数患者中，客观缓解率为29%，病情稳定持续时间超过1年。当FUDR输注调节为昼夜节律时，毒性显著降低。在转移性肾细胞癌患者中进行的一项多中心试验中，患者被随机分配至平坦或昼夜调节的FUDR输注组。这项研究证实了毒性和剂量强度的显著差异，有利于昼夜节律调整组。激素难治性转移性前列腺癌已经用昼夜定时FUDR化疗治疗;然而，没有客观反应。生物制剂如干扰素-α和IL-2在转移性肾细胞癌中显示出低但有效的疾病控制，然而，具有很大的毒性。这些细胞因子中的每一种在模型系统中显示出昼夜节律阶段依赖性毒性和功效。总之，24小时内蒽环类、铂类和氟嘧啶类药物治疗的时间与这些药物治疗妇科和泌尿生殖系统癌症的毒性治疗比相关。版权所有（C）2002 Marcel Dekker，Inc.
The circadian timing of surgery, anticancer drugs, radiation therapy, and biologic agents can result in improved toxicity profiles, tumor control, and host survival. Optimally timed cancer chemotherapy with doxorubicin or pirarubicin (06:00h) and cisplatin (18:00h) enhanced the control of advanced ovarian cancer while minimizing side effects, and increased the response rate in metastatic endometrial cancer. Therapy of metastatic bladder cancer with doxorubicin-cisplatin was made more tolerable by this same circadian approach resulting in a 57% objective response rate. This optimally timed therapy is also effective in the adjuvant setting, decreasing the expected frequency of metastasis from locally advanced bladder cancer. Circadian fluorodeoxyuridine (FUDR) continuous infusion (70% of the daily dose given between 15:00h and 2 1: 00h) has been shown effective for metastatic renal cell carcinoma resulting in 29% objective response and stable disease of more than 1 yr duration in the majority of patients. Toxicity is reduced markedly when FUDR infusion is modulated to circadian rhythms. In a multicenter trial in patients with metastatic renal cell cancer, patients were randomized to a flat or a circadian-modified FUDR infusion. This study confirmed a significant difference in toxicity and dose intensity, favoring the circadian-modified group. Hormone refractory metastatic prostate cancer has been treated with circadian-timed FUDR chemotherapy; however, without objective response. Biological agents such as interferon-alpha and IL-2 have shown low but effective disease control in metastatic renal cell cancer, however, with much toxicity. Each of these cytokines shows circadian stage dependent toxicity and efficacy in model systems. In summary, the timing of anthracycline, platinum, and fluoropyrimidine-based drug therapies during the 24h is relevant to the toxic therapeutic ratio of these agents in the treatment of gynecologic and genitourinary cancers. Copyright (C) 2002 by Marcel Dekker, Inc.