Abstract
Lipoplatin is a liposome encapsulated form of cisplatin. Phase I studies on Lipoplatin showed an excellent toxicity profile of the compound. Therefore we performed a phase II trial in heavily pre-treated patients with advanced non–small cell lung cancer (NSCLC).
This was an open label single-arm trial in patients with NSCLC with stage IV disease already pre-treated with first line chemotherapy. 63% of these patients were pre-treated with platinum containing regimens. Statistical analysis was performed with the SPSS statistical program (version 11.0). Survival curves were estimated by the Kaplan Meyer method. We administered Lipoplatin at the dose of 100 mg/m2 every 14 days as second line chemotherapy. The primary endpoint was the response rate. The secondary endpoints were safety, time to progression and overall survival.
Nineteen patients with stage IV NSCLC, the median age being 64 were treated. Fifteen patients completed at least six cycles and were evaluated for response and toxicity. Four patients completed one cycle of therapy and were evaluated only for toxicity. We obtained one partial response (5.2%) and three stable diseases (15.9%). Median time to progression was 4 months and median survival time was 7.2 months.
In this study lipoplatin as second line treatment showed a lower activity in comparison to other drugs, but the same overall survival. New phase II studies with escalation of the dosage should be considered.
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References
Rosenberg B, VanCamp L, Trosko JE, Mansour VH. Platinum compounds: a new class of potent antitumor agents. Nature 1969;222:385–6.
McKeage MJ. Comparative adverse effect profiles of platinum drugs. Drug Saf 1995;13:228–44.
Arany I, Safirstein RL. Cisplatin nephrotoxicity. Semin Nephrol 2003;23:460–4.
Townsend DM, Deng M, Zhang L, Lapus MG, Hanigan MH. Metabolism of cisplatin to a nephrotoxin in proximal tubule cells. J Am Soc Nephrol 2003;14:1–10.
Humes HD. Insights into ototoxicity. Analogies to nephrotoxicity. Ann NY Acad Sci 1999;884:15–8.
Caraceni A, Martini C, Spatti G, Thomas A, Onofrj M. Recovering optic neuritis during systematic cisplatin and carboplatin chemotherapy. Acta Neurol Scand 1997;96:260–1.
Ali BH, Al Moundhri MS. Agents ameliorating or augmenting the nephrotoxicity of cispla-tin and other platinum compounds: a review of some recent research. Food Chem Toxicol 2006;44:1173–83.
Boulikas T, Vougiouka M. Cisplatin and platinum drugs at the molecular level. Oncol Rep 2003;10:1663–82.
Stathopoulos GP, Boulikas T, Vougiouka M, et al. Pharmacokinetics and adverse reactions of new liposomal cisplatin (Lipoplatin): phase I study. Oncol Rep 2005;13:589–95.
Boulikas T. Low toxicity and activity of a novel liposomal cisplatin (lipoplatin) in mouse xenografts. Oncol Rep 2004;12:3–12.
Boulikas T, Stathopoulos GP, Volakakis N, Vougiouka M. Systemic Lipoplatin infusion results in preferential tumor uptake in human studies. Anticancer Res 2005;25:3031–9.
Bandak S, Goren D, Horowitz A, Tzemach D, Gabizon A. Pharmacological studies of cis-platin encapsulated in long-circulating liposomes in mouse tumor models. Anticancer Drugs 1990;10:911–20.
Devarajan P, Tarabishi R, Mishra J, et al. Low renal toxicity of lipoplatin compared to cisplatin in animals. Anticancer Res 2004;24:2193–200.
Gormley PE, Bull JM, LeRoy AF, Cysyk R. Kinetics of cis-dichlorodiammineplatinum. Clin Pharmacol Ther 1979;25:351–7.
Belt RJ, Himmelstein KJ, Patton TF, Bannister SJ, Sternson LA, Repta AJ. Pharma-cokinetics of non-protein-bound platinum species following administration of cis-dichloro-diammineplatinum(II). Cancer Treat Rep 1979;63:1515–21.
Jehn CF, Boulikas T, Kourvetaris A, Possinger K, Lüftner D. Pharmacokinetics of liposomal cisplatin (lipoplatin) in combination with 5-FU in patients with advanced head and neck cancer: first results of a phase III study. Anticancer Res 2007;27:471–5.
Stathopoulos GP, Boulikas T, Vougiouka M, Rigatos SK, Stathopoulos JG. Liposomal cis-platin with gemcitabine in pretreated advanced pancreatic cancer patients: a phase I–II study. Oncol Rep 2006;15:1201–4.
Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000;18:2095–103.
Gandara DR, Vokes E, Green M, et al. Activity of docetaxel in platinum-treated non-small-cell lung cancer. Results of a phase II multicenter trial. J Clin Oncol 2000;18:131–5.
Fossella F V, Lee JS, Shin DM, et al. Phase II study of docetaxel for advanced or metastatic platinum refractory non-small-cell lung cancer. J Clin Oncol 1995;13:645–51.
Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004;22:1589–97.
Smith J. Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cncer. Clin Ther 2005;27:1513–34.
Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer: molecular and clinical predictors of outcome. N Engl J Med 2005;353:133–44.
Acknowledgments
This work was supported by Istituto Oncologico Romagnolo; project number IOR RN 2003.
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Ravaioli, A. et al. (2009). Is Lipoplatinum Monotherapy an Active Alternative in Second Line Treatment of Metastatic Non–Small Cell Lung Cancer? A Phase II Trial. In: Bonetti, A., Leone, R., Muggia, F.M., Howell, S.B. (eds) Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-459-3_29
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DOI: https://doi.org/10.1007/978-1-60327-459-3_29
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