Cancer chemotherapy cisplatin

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... 

The serendipitous discovery of the antitumor activity of cisplatin opened a huge field of research, leading to significant advances and successes in cancer chemotherapy [181]. Cisplatin and its analogues are reactive complexes that exhibit pharmacokinetic, pharmacodynamic, and toxicological behaviors so closely interdependent as to be all but impossible to untangle. Our focus here is and remains metabolism, but some considerations regarding activity and toxicity are also addressed. 

Zamble DB, Lippard SJ (1995) Cisplatin and DNA repair in cancer chemotherapy. Trends Biochem Sci 20(10) 435-439... 

This is an unusual drug in that it contains a metal atom, platinum (Pt) in this case. Cisplatin reacts with DNA to cross-link bases, disrupting normal DNA structure and function. This agent has found broad use in cancer chemotherapy, including efficacy in tumors of the testis, ovary, bladder, head and neck, thyroid, cervix, and endometrium. It is also active against neuroblastoma and osteogenic sarcoma. 

Antiemetic Aprepitant, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin. 

The earliest combination chemotherapy and radiation trials in nonsmall-cell lung cancer included cisplatin and 5-fluorouracil and concurrent radiation therapy and found survival results comparable to those for sequential chemotherapy and radiation or to daily cisplatin and radiation therapy without surgery (119,121). Phase II studies of stage Ilia and Illb nonsmall-cell lung cancer patients treated with the combination of cisplatin with etoposide and 5 -fluorouracil and either single daily radiation fractionation or twice daily radiation fractionation prior to surgery produced similar clinical results (119,121). Complete surgical resection was accomplished in 70% of the patients, the median survival was 22 mo and the 2-yr survival rate was 45%. 

Dabholkar M, Reed E. Cisplatin. In (Pinedo HM, Longo DL, Chabner BA, eds), Cancer Chemotherapy and Biological Response Modifiers Annual 16, Elsevier Sciences B.V., 1996, pp. 88-110. 

Weiden PL, Piantodosi S. Preoperative chemotherapy cisplatin and fluorouracil and radiation therapy in stage III non-small cell lung cancer A phase II study of the Lung Cancer Study Group. JNatl Cancer Oust 1991 83 266-272. 

E the introduction of different ligands in the amine complexes increases E according to the order I < CN < SCN < Br < Cl < NO2 [159, 160]. Finally, we mention the famous cisplatin, cis-Pt(NH3)Cl2, which is a very powerful cancer chemotherapy drug [161]. Its effect was discovered by Rosenberg [162] accidentally when he investigated the influence of electric field on living cells. He used supposedly inert platinum electrodes to study the suspension of live Escherichia coli bacteria. It was found that, as a consequence of dissolution of Pt, cisplatin was formed which had a devastating effect on the bacteria. 

Olaussen KA, Dunant A, Fouret P et al. lALT Bio Investigators. DNA repair by ERCCl in non-small cell lung cancer and cisplatin-based adjuvant chemotherapy. A Awg/JMed2006 355 983-991. 

Das, B., Yeger, H., Baruchel, H., Freedman, M., Koren, G., and Baruchel, S. (2003). In vitro cytoprotective activity of squalene on a bone marrow versus neuroblastoma model of cisplatin-induced toxicity Implications in cancer chemotherapy. Eur. f. Cancer 39, 2556-2565. 

Finally, the ability of aprepitant to block emesis, a therapeutically relevant endpoint for the ultimate clinical application of the drug, as discussed below, was tested in the presence of several emetogens in the ferret. This species is believed to be a valid animal model for cancer chemotherapy-induced emesis in humans. Aprepitant (1) effectively blocked retching and vomiting due to cisplatin, apomorphine, and morphine at a dose of 3.0 mg/kg p.o. and 0.3 mg/kg i.v. (in the case of cisplatin).8... 

Figure 22.11. Structures of platinum compounds. Cisplatin and carboplatin are active agents used in cancer chemotherapy. Transplatin is inactive against tumors.

It has recently been shown that 2,2-bipyridine forms the complex (11). The importance of this structure is that it demonstrates the possibility of carboxylatorhodium(II) complexes acting in the same way as the well-known cisplatin (m-[PtCl2(NH3)2]) in cancer chemotherapy see... 

Andrews P, Albright K. 1991. Role of membrane ion transport in cisplatin accumulation. Paper presented at the Platinum and other metal coordiantion compounds in cancer chemotherapy. 

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