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.

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