Cisplatin history

Cisplatin, (ds-[PtCl2(NH3)2], also known as cis-DDP) ((1), Figure 2) is perhaps the best known example of a small molecule metal-containing drug. The clinically used platinum complexes are shown in Figure 2. The history of the discovery and development of cisplatin remains a remarkable scientific story.33 Its use and effectiveness in cancer chemotherapy since the entry into the clinic in the late 1970s has been thoroughly documented.34-36 Cisplatin is cited for treatment of... 

Antitumor drugs cisplatin as, history, 37 175-179 platinum compounds future studies, 37 206-208 resistance to, 37 192-193 second-generation, 37 178 Antiviral agents, 36 37-38 AOR, see Aldehyde oxidoreductase Aphanothece sacrum, ferredoxins, amino acid sequence, 38 225-227 Apo-calcylin, 46 455 Apo-caldodulin, 46 449-450 Apoenzyme, 22 424 Apoferritin biosynthesis, 36 457 cystalline iron core, 36 423 Fe(III)distribution, 36 458-459 Fe(II) sequestration, 36 463-464 ferroxidase centers, 36 457-458 iron core reconstruction in shell, 36 457 mineralization, 36 25 Mdssbauer spectra, 36 459-460 optical absorbance spectra, 36 418-419 subunit conformation and quaternary structure, 36 470-471... 

Editor s comment This article is taken in large part from a review article published more than twenty years ago in Interdisciplinary Science Reviews, Vol. 3, No. 2, pp 134-147 (1978). It tells the story of the discovery of cisplatin and reflects on its possible mode of action as an antitumor agent. While some of the ideas may have been revised or discarded today, the article represents a unique personal account of the discovery and at the same time is a beautiful example of science history. The chapter on the clinical results has been deleted, since the present status is covered in an up-to-date manner in this book s contribution by O Dwyer and co-workers. The editor wishes to thank John Wiley Sons Limited for permission to reproduce this work. 

In 86 patients treated with cisplatin-based chemotherapy for testicular cancer, cumulative exposure (over 400 mg/m ) and a previous history of noise exposure were significant susceptibility factors for irreversible ototoxicity high doses of vincristine (greater than 6 mg/m ) significantly increased the risk of reversible ototoxicity (287). 

Lamivudine inhibits the intracellular phosphorylation of zalcitabine and antagonizes zalcitabine s antiretroviral activity in vitro, although the clinical significance of this interaction is unknown. Probenecid increases the zalcitabine AUC by about 50%, probably through inhibition of tubular secretion cimetidine increases the AUC by 36% via an unknown mechanism. Zalcitabine should be avoided in patients with a history of pancreatitis or neuropathy because the risk and severity of both complications increase. Coadministration of other drugs that cause pancreatitis or neuropathy also will increase the risk and severity of these symptoms. Ethambutol, isoniazid, vincristine, cisplatin, and pentamidine, as well as the antiretroviral drugs didanosine and stavudine, therefore, should be avoided. 

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