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Chemotherapy topoisomerase inhibitors

Risk factors for the development of AML include exposure to environmental toxins, Hispanic ethnicity, and genetics.6 Of greater concern is the increased prevalence of AML as a secondary malignancy, resulting from chemotherapy and radiation treatment for other cancers. Alkylating agents, such as ifosfamide and cyclophosphamide, and topoisomerase inhibitors, such as etoposide, are linked to an increased risk of myelodysplastic syndrome (MDS) and AML.8... [Pg.1399]

Topotecan hydrochloride is a DNA topoisomerase inhibitor. Topotecan hydrochloride is an antitumor drug with topoisomerase I-inhibitory activity. It is indicated in metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy small-cell-lung-cancer-sensitive disease after failure of first-line chemotherapy. [Pg.698]

Chemotherapy was first used for the treatment of advanced lymphomas in the 1940s [1], Since then several classes of chemotherapeutic compounds such as alkylating agents, antimetabolites, anthracyclines, plant alkaloids, and later topoisomerase inhibitors and taxanes have been identified or synthesized to treat various forms of cancer [2, 3], Although numerous in vitro and animal studies have demonstrated their effectiveness in inducing cancer cell death (cytotoxic) or cell growth arrest (cytostatic), these promising anticancer activities seen in the controlled environment of the laboratory frequently do not translate well into the expected clinical outcomes [4-8]. [Pg.121]

Hansch and Verma contribute to the quantitative structure-activity relationship (QSAR) analysis of heterocyclic topoisomerase I and II inhibitors. These inhibitors, known to inhibit either enzyme, act as antitumor agents and are currently used in chemotherapy and in clinical trials. [Pg.325]

Combination chemotherapy is the standard approach to stage III and stage IV disease. Randomized clinical studies have shown that the combination of paclitaxel and cisplatin provides survival benefit compared with the previous standard combination of cisplatin plus cyclophosphamide. More recently, several studies have shown that carboplatin and paclitaxel yields clinical results similar to what is achieved with the cisplatin plus paclitaxel combination however, because of reduced toxicity and greater ease of administration, carboplatin plus paclitaxel has now become the treatment of choice. In patients who present with recurrent disease, the topoisomerase I inhibitor topotecan, the alkylating agent altretamine, and liposomal doxorubicin are used as single agent monotherapy. [Pg.1320]

Cositecan (Karenitecin , BNP 1350) 54 (BioNumerik and ASKA Pharmaceutical) is currently being evaluated in a Phase III trial for the treatment of patients with advanced ovarian cancer who have become resistant to platinum and taxane drugs.110 Cositecan 54,111 114 which is also being evaluated against solid tumours in a Phase I trial, is an orally bioavailable, lipophilic 7-[2-(tri-methylsilyl)ethyl] derivative of camptothecin 55 which is less sensitive to both common and camptothecin-specific resistance mechanisms. Camptothecin 55 was first isolated in 1958 from Camptotheca acuminata (Nyssaceae) and its structure was reported in 1966.115 117 Camptothecin 55 was later shown to be a topoisomerase I inhibitor two camptothecin derivatives, topotecan and iri-notecan, are approved for chemotherapy use. [Pg.333]

Hande KR. Topoisomerase II inhibitors. In Giaccone G, Schilsky R, Sondel P, editors. Cancer Chemotherapy and Biological Response Modifiers. Amsterdam Elsevier, 2003 103-25. [Pg.3466]

The isoquinoline derivate camptothecin (115), a well known antineoplastic drug and a topoisomerase I inhibitor, showed antiprotozoal activity when tested against L. donovani, T. cruzi and T. b. brucei with EC50 values of 1.5, 1.6 and 3.6 fiM [132, 133]. For these parasites, camptothecin is an important lead for much-needed new chemotherapy, as well as being a valuable tool for further study of topoisomerase I activity. [Pg.825]

The podophyllotoxin (Fig. 20.22) was isolated from the American mandrake Podophyllum pelatum), which had been traditionally used by American Indians as a laxative and anthelmintic, in 1880. It was subsequently shown to be a potent cytotoxic agent but was too toxic for use in cancer chemotherapy. Chemists at Sandoz in the 1950s further investigated Podophyllum species for analogues of podophyllotoxin. This eventually led to the development of the semi-synthetic compounds tenipinoside and etoposide (Fig. 21.22). These agents are topoisomerase II inhibitors. Teniposide is more cytotoxic than etoposide although it is not orally bioavailable. ... [Pg.437]


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