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Research ArticleClinical Studies

Systemic Lipoplatin Infusion Results in Preferential Tumor Uptake in Human Studies

TENI BOULIKAS, GEORGIOS P. STATHOPOULOS, NIKOLAOS VOLAKAKIS and MARIA VOUGIOUKA
Anticancer Research July 2005, 25 (4) 3031-3039;
TENI BOULIKAS
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  • For correspondence: teni@regulon.org
GEORGIOS P. STATHOPOULOS
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NIKOLAOS VOLAKAKIS
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MARIA VOUGIOUKA
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Abstract

Lipoplatinì, a liposomal formulation of cisplatin, was developed with almost negligible nephrotoxicity, ototoxicity and neurotoxicity, as demonstrated in preclinical and Phase I human studies. A polyethylene-glycol coating of the liposome nanoparticles is supposed to result in tumor accumulation of the drug by extravasation through the altered tumor vasculature. We explored the hypothesis that intravenous infusion of Lipoplatin results in tumor targeting in four independent patient cases (one with hepatocellular adenocarcinoma, two with gastric cancer and one with colon cancer) who underwent Lipoplatin infusion followed by a prescheduled surgery ~20 h later. Direct measurement of the platinum levels in specimens from the excised tumors and normal tissues showed that the total platinum levels were on average 10-50 times higher in malignant tissue compared to the adjacent normal tissue specimens; most effective targeting was observed in colon cancer, with an accumulation up to 200-fold higher in colon tumors compared to normal colon tissue. Of the several surgical specimens, gastric tumors displayed the highest levels of total platinum suggesting Lipoplatin as a candidate anticancer agent for gastric tumors; gastric tumor specimens had up to 260 micrograms platinum /g tissue, that was higher than any tissue level in animals treated at much higher doses. Fat tissue displayed a high accumulation of total platinum in surgical specimens in three different patients, correlating to the lipid capsule of cisplatin in its Lipoplatin formulation. It was also inferred that normal tissue had more platinum trapped in the tissue but not reacted with macromolecules, whereas tumor tissue displayed platinum that reacted with cellular macromolecules; the data were consistent with a model where Lipoplatin damages more tumor compared to normal cells. In conclusion, Lipoplatin has the ability to preferentially concentrate in malignant tissue both of primary and metastatic origin following intravenous infusion to patients. In this respect, Lipoplatin emerges as a very promising drug in the arsenal of chemotherapeutics.

  • Lipoplatin
  • cisplatin
  • tumor targeting
  • gastric cancer
  • colon cancer
  • hepatocellular cancer

Footnotes

  • Received February 23, 2005.
  • Accepted April 25, 2005.
  • Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 25 (4)
Anticancer Research
Vol. 25, Issue 4
1 Jul 2005
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Systemic Lipoplatin Infusion Results in Preferential Tumor Uptake in Human Studies
TENI BOULIKAS, GEORGIOS P. STATHOPOULOS, NIKOLAOS VOLAKAKIS, MARIA VOUGIOUKA
Anticancer Research Jul 2005, 25 (4) 3031-3039;

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Systemic Lipoplatin Infusion Results in Preferential Tumor Uptake in Human Studies
TENI BOULIKAS, GEORGIOS P. STATHOPOULOS, NIKOLAOS VOLAKAKIS, MARIA VOUGIOUKA
Anticancer Research Jul 2005, 25 (4) 3031-3039;
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