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Nedaplatin

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General Features                  Clinical Study                  Chemical Intervention                 Pharmacological Aspects                 
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GENERAL FEATURES

Name: Nedaplatin
Generic Names: 254-S[1], [2],[3]
NSC 375101D[2]
(Glycolato-O, O')diammineplatinum(II)[4]
Trade Names:
IUPAC name: cis-diammine(glycolato)-platinum)(II)[1]
Molecular Formula:
Molecular Weight:
Structure: [5], [6], [7], [8]
Functional Group/
chemical
constitution:
nedaplatin possess glycolate ring bound to the platinum atom as a bidentate ligand[3]
nedaplatin has same ammine carrier ligands as in cisplatin, but has different leaving group, consisting of a five-membered ring structure in which glycolate is bound to the platinum ion as a bidentate ligand[8]
Chemical Nature: platinum complex[1], platinum analogue[3], cisplatin analogue[7]
It has been reported to be about 10-fold more soluble in water than cisplatin[9]
Actions
& Indications:
Pharmcological Action-
second-generation antineoplastic platinum complex[10]
Therapeutic benefits/Indications:
Response rates for nedaplatin(100 mg/m2 repeated every 4 weeks) in phase II study obtained were 42.2% for head & neck cancer, 40.9% for small cell lung cancer (SCLC), 20.5% for non-SCLS (NSCLC), 12.5% for breast cancer, 51.7% for esophageal cancer, 8.3% for stomach cancer. 0 for colon cancer, 38.1% for bladder cancer, 14.3% for pyelo-ureter tract ca., 18.8% for prostatic cancer, 80.0% for testicular tumor, 37.3% for ovarian cancer, 46.3% for cervical cancer[11].
nedaplatin is used as an effective anti-tumor agent with reduced toxicities in patients with esophageal cancer, uterine cervical cancer, head and neck cancer, urothelial cancer [8]
Preclinical study-
nedaplatin showed less renal and gastrointestinal, non-hematological toxicities as compared to cisplatin with superior therapeutic indices in preclinical stiudies[1]
Of 36 human ovarian tumor samples studied, 28% of cancers resistant to cisplatin were sensitive to nedaplatin, that is, nedaplatin was shown to be crossresistant with cisplatin in vitro[5]
nedaplatin is claimed to be useful as alternative to cisplatin for treatment of esopaheal cancer as its shows low nephro- and digestive toxicity[12]
Notes: concurrent nedaplatin with or without taxanes against weekly cisplatin needs to be tested in futurein welll designed phase III trials, as suggested by a review[13]
Nedaplatin can cause nephrotoxicity at human therapeutic dose without hydration and which can be ameliorated by pre- and post-hydration[10]
Creatinine clearance was found to be a significant covariate of clearance and body weight was found to be a significant covariate of volume of distribution, in a study with adult patients given nedaplatin IV infusion[14]
nedaplatin is developed in Japan[3], in 1983 by Shionogi pharmaceutical company[8]
reduced nephrotoxicity of nedapatin is said to be due to reduced accumulation in the proximal tubules due to its lower affinity for transporters(Oct2 and MATE family)[15]
REFERENCES
1. Ota K et al, Phase I study of a new platinum complex 254-S, cis-diammine (glycolato)-platinum (II). Gan To Kagaku Ryoho. 1992;19(6):855-61.
http://www.ncbi.nlm.nih.gov/pubmed/1605663
2. Sasaki Y et al, Prediction of the antitumor activity of new platinum analogs based on their ex vivo pharmacodynamics as determined by bioassay. Cancer Chemother Pharmacol. 1991;27(4):263-70.
http://dx.doi.org/10.1007/BF00685110
3. Candelaria M et al, Radiosensitizers in cervical cancer. Cisplatin and beyond. Radiat Oncol. 2006;8(1):15.
http://dx.doi.org/10.1186/1748-717X-1-15
4. Kameyama Y et al, Nephrotoxicity of a new platinum compound, 254-S, evaluated with rat kidney cortical slices. Toxicol Lett. 1990;52(1):15-24.
http://dx.doi.org/10.1016/0378-4274(90)90161-E
5. Alberts DS et al, In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human ovarian cancers. Cancer Chemother Pharmacol. 1997;39(6):493-7.
http://dx.doi.org/10.1007/s002800050604
6. Tsuda H et al, Phase I–II study of irinotecan (CPT-11) plus nedaplatin (254-S) with recombinant human granulocyte colony-stimulating factor support in patients with advanced or recurrent cervical cancer. Br J Cancer. 2004;91(6):1032-7.
http://dx.doi.org/10.1038/sj.bjc.6602076
7. Monk BJ et al, In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human cervical cancers. Gynecol Oncol. 1998;71(2):308-12.
http://dx.doi.org/10.1006/gyno.1998.5140
8. Shimada M, Itamochi H, Kigawa J, Nedaplatin: a cisplatin derivative in cancer chemotherapy. Cancer Manag Res. 2013;5:67-76.
http://dx.doi.org/10.2147/CMAR.S35785
9. Yamanaka H et al, Nedaplatin and 5-FU combined with radiation in the treatment for esophageal cancer. Jpn J Thorac Cardiovasc Surg. 1998;46(10):943-8.
http://dx.doi.org/10.1007/BF03217851
10. Uehara T et al, Time course of the change and amelioration of nedaplatin-induced nephrotoxicity in rats. J. Appl. Toxicol. 2008; 28: 388–398
http://dx.doi.org/10.1002/jat.1292
11. Ota K, Nedaplatin. Gan To Kagaku Ryoho. 1996;23(3):379-87.
http://www.ncbi.nlm.nih.gov/pubmed/8712835
12. Inaba H et al, Clinical study of the combination of small amount of nedaplatin (CDGP)/5-FU with radiation for the treatment of esophageal cancer. Nihon Shokakibyo Gakkai Zasshi. 2002;99(10):1191-6.
http://www.ncbi.nlm.nih.gov/pubmed/12415854
13. Gandhi AK, Novel agents and treatment techniques to enhance radiotherapeutic outcomes in carcinoma of the uterine cervix. Ann Transl Med. 2016;4(3):49.
http://dx.doi.org/10.3978/j.issn.2305-5839.2015.10.08
14. Ishibashi T, Yano Y, Oguma T, Population pharmacokinetics of platinum after nedaplatin administration and model validation in adult patients. Br J Clin Pharmacol. 2003;56(2):205-13.
http://dx.doi.org/10.1046/j.1365-2125.2003.01871.x
15. Uehara T et al, Comparative Nephrotoxicity of Cisplatin and Nedaplatin: Mechanisms and Histopathological Characteristics. J Toxicol Pathol. 2011;24(2):87-94.
http://dx.doi.org/10.1293/tox.24.87