Anticancer drugs carboplatin

The kinetic behavior of the anticancer drug Carboplatin, [Pt(NH3)2(biL)] (biL = 1,1-cyclobutanedicarboxylate), has been examined. In the absence of acid and other nucleophiles, the complex is quite inert. With addition of chloride. 

O Dwyer, P. J. Stevenson, J. P. Johnson, S. W. Clinical Status of Cisplatin, Carboplatin, and Other Platinum-based Antitumor Drugs. In Cisplatin Chemistry and Biochemistry of a Leading Anticancer Drug Lippert, B., Ed. Wiley-VCH New York 1999, pp 31-72. 

In 1965 Rosenberg et al. (8, 9) accidentally discovered the antiproliferative effect of cis-diammine platinum complexes, which led to the first clinical trials of cis-[PtCl2(NH3)2] 1 in 1971 and resulted in the clinical use of cisplatin worldwide. Cisplatin and carboplatin 2 are the most widely used anticancer drugs, and two other analogs, nedaplatin 3 and oxaliplatin 4 (chiral centers indicated), have recently been approved for clinical use in Japan and France, respectively. 

O. Rixe, W. Ortuzar, M. Alvarez, R. Parker, E. Reed, K. Pauli, T. Fojo, Oxaliplatin, Tet-raplatin, Cisplatin, and Carboplatin Spectrum of Activity in Drug-Resistant Cell Lines and in the Cell Lines of the NCI s Anticancer Drug Screen Panel , Biochem. Pharmacol. 1996, 52, 1855 - 1865. 

Two of the most important platinum anticancer drugs are cisplatin (2.13) and carboplatin (2.14). Cisplatin is effective against testicular tumours, ovarian carcinoma and some other types of cancer, but relatively inactive against breast and lung cancers it is also a very toxic compound. Side effects include loss of high-frequency hearing, neuropathy and nausea. Kidney damage may also result, but is minimised... 

Cisplatin [SIS pla tin] is a member of the platinum coordination complex class of anticancer drugs. Because of cisplatin s severe toxicity, carboplatin [KAR bow pla tin] was developed. The therapeutic effectiveness of the two drugs is similar but their pharmacokinetics, patterns of distribution and dose-limiting toxicities differ. Cisplatin has synergistic cytotoxicity with radiation and other chemotherapeutic agents. 

Chemotherapy refers to drug administration with highly serious side effects, such as nausea, hand and foot rashes, mouth sores, and increased risk of infection, easy bruising, and so on. Therefore, liposomal carriers have been used in order to improve the drug s biodistribution and protect the patient from those side effects. The main anticancer drugs used to treat ovarian cancer are carboplatin and cisplatin, paclitaxel, topotecan, and lurtotecan. PEGylated liposomal doxorubicin has been approved as a regimen for patients with metastatic ovarian cancer refractory to both paclitaxel and platinum based-therapy [449],... 

Rixe O, Ortuzar W, Alvarez M et al. Oxaliplatin, tetraplatin, cisplatin, and carboplatin Spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute s Anticancer Drug Screen panel. Biochem Pharmacol 1996 52 1855-65. 

Safirstein R, Deray G. Anticancer Cisplatin/carboplatin. in DeBroe ME, Porter GA, Bennett WM, Verpooten GA (eds) Clinical Nephrotoxins. Renal injury from drugs and chemicals. Kluwer Academic, Dordrecht, 261-271,1998. 

From the animal screens emerged the set of structure-activity relationships enumerated earlier (Section IV.E.l). Both cisplatin and carboplatin conform to these rules, and to date no compounds with demonstrably better antitumor activity have been tested in humans. The decision to move an experimental drug into the clinic is a difficult one, however, and it may be that molecules such as cis-[Pt(NH3)2(4-Br-py)Cl]Cl (see Section V.D.V.c) would be effective for tumors that are refractive to cisplatin chemotherapy. In any case, the foregoing chain of events, from studying the effects of a compound on cells in culture through animal screens and eventually to humans, constitutes the principal route for introducing a new anticancer drug. The process can take more than a decade. 

This potent anticancer drug is now widely used in chemotherapy in association with several other drugs (e.g., vinblastine, methotrexate, carboplatine, ifosfamide, or etoposide) in the treatment of Hodgkin s disease (9), of head and neck cancers (JO, 11), of disseminated germ cell tumors (12), and of poor-prognosis epidemic Kaposi s sarcoma (13) (for previous articles on the clinical use of BLM, see references listed in Refs. 9-13). 

Platinum-containing alkylating anticancer drug. Used for solid tumors (eg, testes, lung). Tox Neurotoxic and nephrotoxic. Carboplatin is similar. 

Fig.1 Selected platinum-based anticancer compoimds a cisplatin second generation anticancer drugs b carboplatin, c nedaplatin and d oxaliplatin and novel complexes with interesting dinical properties such as the orally administered e satraplatin and complexes designed to overcome cisplatin resistance f trans-dipyridine dichloroplatinum and g a platinum amino phosphine complex...

Next to cisplatin (Scheme 8.22), carboplatin (Scheme 8.23) is the most widely used metal-containing anticancer drug. Although it is similar to cisplatin in its cell-killing ability, it shows moderate effectiveness with some malignancies that... 

A number of platinum(II) complexes such as cisplatin and carboplatin Fig. 4.14 are important anticancer drugs. For example, cisplatin (4.12) is effective in the treatment of ovarian and testicular cancers. 

Fig. 2.1 Platlnum(ll) complexes approved for clinical use as anticancer drugs (1) dsplatin, (2) carboplatin, (3) nedaplatin, (4) oxaliplatin.

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