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Comparison of the Anti-tumor Effects of Two Platinum Agents (Miriplatin and Fine-Powder Cisplatin)

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Abstract

Purpose

This study was designed to evaluate the anti-tumor effects of miriplatin-lipidol and fine-powder cisplatin–lipiodol suspensions.

Methods

Assessment of the cytotoxicity of two drugs was performed: a soluble derivative of miriplatin (DPC) and fine-powder cisplatin. We randomly divided 15 rabbits with transplanted VX2 liver tumors into three equal groups. They were infused via the proper hepatic artery with a miriplatin-lipiodol suspension (ML), a fine-powder cisplatin-lipiodol suspension (CL), or saline (control) and the tumor growth rate was determined on MR images acquired before and 7 days after treatment. The concentration of platinum (PCs) in blood was assayed immediately, and 10, 30, and 60 min, and 24 h and 7 days after drug administration. Its concentration in tumor and surrounding normal liver tissues was determined at 7 days postadministration.

Results

At high concentrations, fine-powder cisplatin exhibited stronger cytotoxicity than DPC. At low concentrations, both agents manifested weak cytotoxicity. While there was no difference between the tumor growth rate of the ML and the CL groups, the difference between the controls and ML- and CL-treated rabbits was significant. The blood PCs peaked at 10 min and then gradually decreased over time. On the other hand, no platinum was detected at any point after the administration of ML. There was no difference between the ML and CL groups in the PCs in tumor tissues; however, in normal hepatic tissue, the PCs were higher in ML- than CL-treated rabbits.

Conclusions

We confirmed the anti-tumor effect of ML and CL. There was no significant difference between the anti-tumor effect of ML and CL at 7 days postadministration.

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References

  1. Kinami Y, Miyazaki I (1978) The superselective and the selective one shot methods for treating inoperable cancer of the liver. Cancer 41:1720–1727

    Article  PubMed  CAS  Google Scholar 

  2. Shibata J, Fujiyama S, Sato T, Kishimoto S et al (1989) Hepatic arterial injection chemotherapy with cisplatin suspended in an oily lymphographic agent for hepatocellular carcinoma. Cancer 64:1586–1594

    Article  PubMed  CAS  Google Scholar 

  3. Shimamura Y, Gunven P, Takenaka Y et al (1988) Combined peripheral and central chemoembolization of liver tumors. Experience with lipiodol-doxorubicin and gelatin sponge (L-TAE). Cancer 61:238–242

    Article  PubMed  CAS  Google Scholar 

  4. Ohnishi K, Sugita S, Nomura F et al (1987) Arterial chemoembolization with mitomycin C microcapsules followed by transcatheter hepatic artery embolization for hepatocellular carcinoma. Am J Gastroenterol 82:876–879

    PubMed  CAS  Google Scholar 

  5. Okusaka T, Okuda S, Ueno H et al (2002) Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma. Oncology 62:228–233

    Article  PubMed  CAS  Google Scholar 

  6. Okita K (2006) Clinical aspects of hepatocellular carcinoma in Japan. Intern Med 45(5):229–233

    Article  PubMed  Google Scholar 

  7. Lau WY, Lai EC (2008) Hepatocellular carcinoma: current management and recent advances. Hepatobiliary Pancreat Dis Int 7(3):237–257

    PubMed  Google Scholar 

  8. Achenbach T, Seifert JK, Pitton MB et al (2002) Chemoembolization for primary liver cancer. Eur J Surg Oncol 28(1):37–41

    Article  PubMed  CAS  Google Scholar 

  9. Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37(2):429–442

    Article  PubMed  CAS  Google Scholar 

  10. Watban JA, Rodesch G, Alvarez H et al (1995) Transarterial embolization of vein of Galen aneurysmal malformation after unsuccessful stereotactic radiosurgery. Report of three cases. Childs Nerv Syst 11(7):406–408

    Article  PubMed  CAS  Google Scholar 

  11. Hyare H, Desigan S, Brookes JA, Guiney MJ et al (2007) Endovascular management of major arterial hemorrhage as a complication of inflammatory pancreatic disease. J Vasc Interv Radiol 18(5):591–596

    Article  PubMed  Google Scholar 

  12. Ono Y, Yoshimasu T, Ashikaga R et al (2000) Long-term results of lipiodol-transcatheter arterial embolization with cisplatin or doxorubicin for unresectable hepatocellular carcinoma. Am J Clin Oncol 23:564–568

    PubMed  CAS  Google Scholar 

  13. Venook AP, Stagg RJ, Lewis BJ et al (1990) Chemoembolization for hepatocellular carcinoma. J Clin Oncol 8:1108–1114

    PubMed  CAS  Google Scholar 

  14. Kawakami A, Yoshioka H, Ohkusa Okafuji T et al (1993) Effects of intrahepatic arterial injection of cisplatin suspended lipiodol on hepatocellular carcinoma. J Jpn Soc Cancer Ther 28:794–803

    Google Scholar 

  15. Malagari K, Chatzimichael K, Alexopoulou E et al (2008) Transarterial chemoembolization of unresectable hepatocellular carcinoma with drug eluting beads: results of an open-label study of 62 patients. Cardiovasc Interv Radiol 31(2):269–280

    Article  Google Scholar 

  16. Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: Efficacy and doxorubicin pharmacokinetics. J Hepatol 46(3):474–481

    Article  PubMed  CAS  Google Scholar 

  17. Yoshikawa M, Ono N, Yodono H et al (2008) Phase II study of hepatic arterial infusion of a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma. Hepatol Res 38:474–483

    Article  PubMed  CAS  Google Scholar 

  18. Kishimoto S, Miyazawa K, Terakawa Y et al (2000) Cytotoxicity of cis-[((1R, 2R)-1,2-Cyclohexanediamine-N,N′) bis (myristato)]-platinum (II) suspended in lipiodol in a newly established cisplatin resistant rat hepatoma cell line. Jpn J Cancer Res 91:1326–1332

    Article  PubMed  CAS  Google Scholar 

  19. Kishimoto S, Noguchi T, Yamaoka T et al (2000) In vitro cytotoxicity of cis[((1R, 2R)-1,2-cyclohexanediamine-N,N′)bis(myristato)] platinum(II) suspended in lipiodol in rat hepatoma AH-109A cells and human tumor cell lines. Biol Pharm Bull 23(4):487–491

    Article  PubMed  CAS  Google Scholar 

  20. Wang Z, Zhou J, Fan J et al (2009) Oxaliplatin induces apoptosis in hepatocellular carcinoma cells and inhibits tumor growth. Expert Opin Investig Drugs 18(11):1595–1604

    Article  PubMed  CAS  Google Scholar 

  21. Rathore R, Safran H, Soares G et al (2010) Phase I study of hepatic arterial infusion of oxaliplatin in advanced hepatocellular cancer: a Brown University oncology group study. Am J Clin Oncol 33(1):43–46

    Article  PubMed  CAS  Google Scholar 

  22. Uhm JE, Park JO, Lee J et al (2009) A phase II study of oxaliplatin in combination with doxorubicin as first-line systemic chemotherapy in patients with inoperable hepatocellular carcinoma. Cancer Chemother Pharmacol 63(5):929–935

    Article  PubMed  CAS  Google Scholar 

  23. Haaga JR, Exner AA, Wang Y et al (2005) Combined tumor therapy by using radiofrequency ablation and 5-FU-laden polymer implants: evaluation in rats and rabbits. Radiology 237(3):911–918

    Article  PubMed  Google Scholar 

  24. Wright KC, Yang P, Van Pelt CS et al (2005) Evaluation of targeted arterial delivery of the branched chain fatty acid 12-methyltetradecanoic acid as a novel therapy for solid tumors. J Exp Ther Oncol 5(1):55–68

    PubMed  Google Scholar 

  25. Maeda S, Fujiyama S, Tanaka M et al (2002) Survival and local recurrence rates of hepatocellular carcinoma patients treated by transarterial chemolipiodolization with and without embolization. Hepatol Res 23(3):202–210

    Article  PubMed  CAS  Google Scholar 

  26. Rosenberg B, Van Camp L, Krigas T (1964) Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 205:698–699

    Article  Google Scholar 

  27. Zhang J, Liu D, Li Y et al (2009) Status of non-classical mononuclear platinum anticancer drug development. Mini Rev Med Chem 9(11):1357–1366

    Article  PubMed  CAS  Google Scholar 

  28. Luo FR, Yen TY, Wyrck SD et al (1999) High-performance liquid chromatographic separation of the biotransformation products of oxaliplatin. J Chromatogr B 724:345–356

    Article  CAS  Google Scholar 

  29. Kishimoto S, Noguchi T, Yamaoka T et al (2000) In vitro release of SM-11355, cis[((1R, 2R)-1,2-cyclohexanediamine-N,N′)bis(myristato)] platinum(II) suspended in lipiodol. Biol Pharm Bull 23(5):637–640

    Article  PubMed  CAS  Google Scholar 

  30. Yamashita Y, Taketomi A, Itoh S et al (2010) Phase I/II study of the lipiodolization using DDP-H (CDDP powder; IA-call®) in patients with unresectable hepatocellular carcinoma. Cancer Chemother Pharmacol 65:301–307

    Article  PubMed  CAS  Google Scholar 

  31. Hanada M, Baba A, Tsutsumishita Y et al (2009) Intra-hepatic arterial administration with miriplatin suspended in an oily lymphographic agent inhibits the growth of human hepatoma cells orthotopically implanted in nude rats. Cancer Sci 100(1):189–194

    Article  PubMed  CAS  Google Scholar 

  32. Hanada M, Baba A, Tsutsumishita Y et al (2009) Intra-hepatic arterial administration with miriplatin suspended in an oily lymphographic agent inhibits the growth of tumors implanted in rat livers by inducing platinum-DNA adducts to form and massive apoptosis. Cancer Chemother Pharmacol 64(3):473–483

    Article  PubMed  CAS  Google Scholar 

  33. Yamamoto K, Shimizu T, Narabayashi I (2000) Intra-arterial infusion chemotherapy with lipiodol-CDDP suspension for hepatocellular carcinoma. Cardiovasc Interv Radiol 23:26–39

    Article  CAS  Google Scholar 

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Conflict of interest

All the authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Radiology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan

    Shobu Watanabe, Norihisa Nitta, Shinichi Ohta, Akinaga Sonoda, Hideji Otani, Yuki Tomozawa, Ayumi Nitta-Seko, Keiko Tsuchiya, Toyohiko Tanka, Masashi Takahashi & Kiyoshi Murata

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  1. Shobu Watanabe
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  2. Norihisa Nitta
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  3. Shinichi Ohta
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  4. Akinaga Sonoda
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  7. Ayumi Nitta-Seko
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Correspondence to Shobu Watanabe.

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Watanabe, S., Nitta, N., Ohta, S. et al. Comparison of the Anti-tumor Effects of Two Platinum Agents (Miriplatin and Fine-Powder Cisplatin). Cardiovasc Intervent Radiol 35, 399–405 (2012). https://doi.org/10.1007/s00270-011-0172-4

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  • DOI: https://doi.org/10.1007/s00270-011-0172-4

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