Reference

Phase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia

Phase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia. Seiter, Karen; Feldman, Eric J.; Halicka, H. Dorota; Traganos, Frank; Darzynkiewicz, Zbigniew; Lake, Diana; Ahmed, Tauseef (Division of Oncology/Hematology, New York Medical College, Valhalla, NY, USA).In this study， 123948-87-8 and 147-94-4 are also used. Journal of Clinical Oncology, 15(1), 44-51 (English) 1997 Saunders. CODEN: JCONDN. ISSN: 0732-183X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The purpose of this study is to det. the maximal-tolerated dose (MTD) of topotecan with cytarabine in acute leukemia patients, and to evaluate leukemia cell apoptosis in these patients. Fifty-three patients with acute leukemia not responsive to std. therapy were treated at eight dose levels of topotecan (2.5 mg/M2/d to 7.75 mg/M2/d). Topotecan was given as a 30-min infusion daily with cytarabine 1 g/M2/d, both for 5 days. Using a flow-cytometric technique, the percent apoptotic cells in blood and bone marrow samples was detd., and the cell cycle distribution of the leukemic cells studied. Oropharyngeal mucositis was dose-limiting. The MTD of topotecan was 4.75 mg/M2/d for 5 days in high-risk patients and 7.0 mg/M2/d for 5 days in low-risk patients. The mean percent apoptotic cells in the peripheral blood reached a peak of 18.8%, a median of 48 h following the first dose of topotecan. Patients with higher S-phase fractions, either before treatment or following cytarabine, were more likely to achieve bone marrow aplasia than those with lower S-phase fractions (and, resp.). Clin. responses were seen in four of 39 patients with acute myelogenous leukemia (AML; of whom 32 had received prior high-dose cytarabine), three of six with acute lymphoblastic leukemia (ALL), and one of eight with chronic myelogenous leukemia in blast phase (CML-BP). The recommended phase II dose of topotecan with intermediate-dose cytarabine is 4.75 mg/M2/d for high-risk patients and 7.0 mg/M2/d for low-risk patients. The percentage of cells in S phase was important in detg. response to treatment. .

Potentiation of radiation response in human carcinoma cells in vitro and murine fibrosarcoma in vivo by topotecan, an inhibitor of DNA topoisomerase I

Potentiation of radiation response in human carcinoma cells in vitro and murine fibrosarcoma in vivo by topotecan, an inhibitor of DNA topoisomerase I. Kim, Jae Ho; Kim, Sang Hie; Kolozsvary, Andrew; Khil, Mark S. (Dep. Radiat. Oncol., Henry Ford Hosp., Detroit, MI 48202, USA). Int. J. Radiat. Oncol., Biol., Phys., 22(3), 515-18 (English) 1992. CODEN: IOBPD3. ISSN: 0360-3016. DOCUMENT TYPE: Journal CA Section: 8 (Radiation Biochemistry) Section cross-reference(s): 14 DNA topoisomerase I, a nuclear enzyme important for solving topol. problems arising during DNA replication, has been identified as a principal target of a plant alkaloid, 20(s)-camptothecin. In view of the profound biochem. effects of camptothecin and its analogs on DNA replication and the differential cytotoxic effects on human tumors in xenografts, expts. were performed to det. whether topotecan, a camptothecin analog, would potentiate the radiation effects on human carcinoma cells in culture and murine fibrosarcoma in mice. Cell culture studies showed that a dose dependent redn.There are some commonly used reagents with their cas registry numbers 123948-87-8 and 80449-01-0 in this article. in cell survival was obtained with a 4 h exposure of the drug following irradn. of cells. No enhancement of cell killing was seen when cells were treated with the drug before irradn. Preliminary in vivo tumor studies showed a significant radiosensitizing effect of topotecan that was both drug dose (20 mg/kg) and time sequence (4 h before irradn.) dependent. There was no enhanced skin reaction following the combined treatments. .