Furue H
Fourth Dept. of Internal Medicine, Teikyo University.
Gan To Kagaku Ryoho. 1993 Jan;20(1):42-9.
Irinotecan hydrochloride (CPT-11), topotecan, sobuzoxane, NC-190, and IST-622 are unique topoisomerase inhibitors and are investigational in Japan. CPT-11 is a water-soluble, semisynthetic derivative of camtothecin. CPT-11 shows its anticancer activity by inhibiting topoisomerase I activity, now a target of anticancer agents with major interest. Recent clinical trials reveal that CPT-11 is very effective in the treatment of cancer including lung cancer, cervical cancer, ovary cancer, stomach cancer, colon cancer, and non-Hodgkin's lymphoma. Major dose limiting toxicities are leukopenia and diarrhea, and are dose related. Topotecan is an another semisynthetic derivative of camtothecin and is also topoisomerase I inhibitor. Topotecan has undergone phase I clinical evaluations in USA, europe, and recently in Japan. DLF are leukopenia and neutropenia. Topotecan is more hydrophilic than its parent compound and shows lesser protein binding. Renal excretion appears to be the major route of elimination. Sobuzoxane (MST-16) is a unique derivative of dioxopiperazine, an inhibitor of topoisomerase II. In phase II studies, definite anticancer effects are observed in patients with non-Hodgkin's lymphoma and adult T-cell leukemia/lymphoma. Responses are seen even in pretreated cases. Leukopenia is also dose-limiting. Non-hematologic toxicities are mild and include alopecia and G.I. toxicities. NC-190 is a novel benzophenazine derivative with excellent antitumor activities against murine tumors. NC-190 also inhibits topoisomerase II. Now the drug is an early clinical phase II studies in Japan. Toxicities include bone marrow suppression, transient mild to moderate liver enzyme elevation, alopecia and mild G.I. toxicities. Tumor responses are occasionally encountered. IST-622 is a semisynthetic derivative of chartreusin. The drug is an inhibitor of topoisomerase II (and I in high concentration). IST-622 shows excellent, broad anticancer activity against murine tumors. The drug is well absorbed from small intestine. IST-622 is now in phase I clinical trial in Japan.
盐酸伊立替康（CPT - 11）、拓扑替康、sobuzoxane、NC - 190和IST - 622是独特的拓扑异构酶抑制剂，目前正在日本进行研究。CPT - 11是喜树碱的水溶性半合成衍生物。CPT - 11通过抑制拓扑异构酶I的活性发挥抗癌作用，而拓扑异构酶I目前是备受关注的抗癌药物靶点。近期的临床试验表明，CPT - 11在治疗包括肺癌、宫颈癌、卵巢癌、胃癌、结肠癌和非霍奇金淋巴瘤在内的多种癌症方面非常有效。主要的剂量限制性毒性是白细胞减少和腹泻，且与剂量相关。拓扑替康是喜树碱的另一种半合成衍生物，也是拓扑异构酶I抑制剂。拓扑替康在美国、欧洲以及最近在日本都进行了I期临床评估。剂量限制性毒性是白细胞减少和中性粒细胞减少。拓扑替康比其母体化合物更具亲水性，且蛋白结合率较低。肾脏排泄似乎是主要的消除途径。Sobuzoxane（MST - 16）是二氧哌嗪的独特衍生物，是拓扑异构酶II的抑制剂。在II期研究中，在非霍奇金淋巴瘤和成人T细胞白血病/淋巴瘤患者中观察到了明确的抗癌效果。即使是预处理过的病例也有反应。白细胞减少也是剂量限制性毒性。非血液学毒性较轻，包括脱发和胃肠道毒性。NC - 190是一种新型二苯并吩嗪衍生物，对小鼠肿瘤具有优异的抗肿瘤活性。NC - 190也抑制拓扑异构酶II。目前该药物正在日本进行早期II期临床研究。毒性包括骨髓抑制、短暂的轻度至中度肝酶升高、脱发和轻度胃肠道毒性。偶尔会出现肿瘤反应。IST - 622是金丝菌素的半合成衍生物。该药物是拓扑异构酶II（高浓度时也是拓扑异构酶I）的抑制剂。IST - 622对小鼠肿瘤显示出优异的、广泛的抗癌活性。该药物从小肠吸收良好。IST - 622目前正在日本进行I期临床试验。
