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Regional Cancer Therapy. Cancer Drug Discovery and by Peter M. Schlag, Ulrike S. Stein, M.M. Eggermont

By Peter M. Schlag, Ulrike S. Stein, M.M. Eggermont

This quantity presents a organic and pharmacological history for neighborhood melanoma remedy, thoughts and strategies for local treatments, and particular symptoms and effects for various tumor entities. scientific trial strategies and precise therapy protocols also are awarded. This booklet is vital interpreting for researchers and clinicians engaged in looking complicated healing recommendations for melanoma sufferers world wide.

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Raymond E, Chaney SG, Taamma A, Cvitkovic E. Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol 1998;9:1053–1071. 22. Hertzberg RP, Caranfa MJ, Holden KG, et al. Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. J Med Chem 1989;32:715–720. 23. Chabot GG, Abigerges D, Catimel G, et al. Population pharmacokinetics and pharmacodynamics of irinotecan (CPT-11) and active metabolite SN-38 during phase I trials.

5. Gelderblom H, Verweij J, Nooter K, Sparreboom A. Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer 2001;37:1590–1598. 6. Sparreboom A, Van Zuylen L, Brouwer E, et al. Cremophor EL-mediated alteration of paclitaxel distribution in human blood: clinical pharmacokinetic implications. Cancer Res 1999;59:1454–1457. 7. Knemeyer I, Wientjes MG, Au JLS. Cremophor reduces paclitaxel penetration into bladder wall during intravesical treatment. Cancer Chemother Pharmacol 1999;44:241–248.

It might be worthwhile to test the active metabolite SN-38 directly. Oxaliplatin is rapidly absorbed and transformed by nonenzymatic pathways to its biologically active species (24). It mainly exerts its cytotoxic effect by formation of DNA intra- and interstrand crosslinks, hampering DNA replication (29). Substantial dosedependent DNA adduct formation occurs within 1 h. In most studies in which oxaliplatin is administered systemically, hematological toxicity and nephrotoxicity are dose limiting, whereas hepatotoxicity is rarely mentioned.

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