Pantazis P
The Stehlin Foundation for Cancer Research, St. Joseph Hospital, Houston, Texas 77003, USA.
Clin Cancer Res. 1995 Nov;1(11):1235-44.
Water-insoluble camptothecin (CPT) congeners are rapidly establishing themselves as promising anticancer drugs. In vitro, they have exhibited: (a) insensitivity to elevated levels of P-glycoprotein that confers multidrug resistance; (b) selective killing of malignant cells traversing the S-phase of the cell cycle, while leaving viable normal cells, which either are arrested at the S-G2 boundary or continue to divide; (c) no cross-resistance with several other anticancer drugs; and (d) potentiation or enhancement of cytotoxicity when appropriately used in combination with tumor necrosis factor, ionizing radiation, and hyperthermia. In addition, development of cell resistance to water-insoluble CPT congeners in vitro is accompanied by increased sensitivity to other anticancer drugs. Furthermore, water-insoluble CPT congeners have exhibited an unprecedented activity against a wide variety of human tumors xenografted in nude mice by inhibiting growth and inducing regression of carcinomas of the lung, breast, ovary, colon, stomach, pancreas, and prostate, as well as malignant melanoma, lymphoma, and leukemia. More importantly, oral administration of the water-insoluble CPT congeners in clinical studies with cancer patients makes other route(s) of administration unnecessary.
水不溶性喜树碱（CPT）类似物正迅速成为有前景的抗癌药物。在体外，它们表现出：（a）对赋予多药耐药性的高水平P-糖蛋白不敏感；（b）选择性杀死处于细胞周期S期的恶性细胞，而使存活的正常细胞保持活力，这些正常细胞要么停滞在S-G2边界，要么继续分裂；（c）与其他几种抗癌药物无交叉耐药性；（d）与肿瘤坏死因子、电离辐射和热疗联合使用时，可增强细胞毒性。此外，体外对水不溶性CPT类似物产生细胞耐药性的同时，对其他抗癌药物的敏感性增加。此外，水不溶性CPT类似物通过抑制生长并诱导肺癌、乳腺癌、卵巢癌、结肠癌、胃癌、胰腺癌和前列腺癌以及恶性黑色素瘤、淋巴瘤和白血病的消退，对裸鼠体内移植的多种人类肿瘤表现出前所未有的活性。更重要的是，在癌症患者的临床研究中口服水不溶性CPT类似物使得无需其他给药途径。
