This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gelmon, K. A. Articles by Mayer, L. D. Search for Related Content PubMed PubMed Citation Articles by Gelmon, K. A. Articles by Mayer, L. D. Social Bookmarking                            What's this?

Phase I Study of Liposomal Vincristine

From the British Columbia Cancer Agency, Vancouver, University of British Columbia, and Inex Pharmaceuticals, Burnaby, British Columbia, Canada.

Address reprint requests to Karen Gelmon, MD, British Columbia Cancer Agency, Vancouver Centre, 600 West 10th Ave, Vancouver, British Columbia V5Z 4E6, Canada; email kgelmon{at}bccancer.bc.ca

PURPOSE: A phase I study of vincristine encapsulated inside 120-nm-diameter distearoylphosphatidylcholine-cholesterol liposomes was performed. The primary objectives were to determine the maximum-tolerated dose (MTD), recommended phase II dose, toxicity, and pharmacokinetics of liposomal vincristine (ONCO-TCS).

PATIENTS AND METHODS: Twenty-five patients with histologically confirmed malignancies were enrolled and assessable. Vincristine doses were increased from 0.5 mg/m² to 1.0, 1.5, 2.0, 2.4, and 2.8 mg/m² with cohorts of three or more patients per dose level. A total of 64 courses of ONCO-TCS were administered intravenously once every 3 weeks. The pharmacokinetics of total vincristine content in plasma were determined using a high-performance liquid chromatography method.

RESULTS: Patients were treated with vincristine doses up to 2.8 mg/m²; however, 2.4 mg/m² was defined as the MTD and 2.0 mg/m² as the phase II recommended dose. Pain and obstipation were the dose-limiting toxicites. Other toxicities were fever, rigors, fatigue, myalgias, and peripheral neuropathy. Hematologic toxicity was mild. All patients who were treated with doses above 1.5 mg/m² received in excess of 2.0 mg of vincristine, with doses as high as 6.2 mg. One partial response was seen in a patient with pancreatic cancer. Tumor response not meeting partial response criteria was seen in two other patients. Pharmacokinetic studies revealed significantly elevated concentrations of total vincristine, but parameters varied and were not directly correlated with toxicity or response.

CONCLUSION: The ability to administer elevated doses of vincristine, as well as indications of efficacy, suggests that ONCO-TCS warrants further clinical investigation in a phase II setting.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. O. Noble, M. T. Krauze, D. C. Drummond, Y. Yamashita, R. Saito, M. S. Berger, D. B. Kirpotin, K. S. Bankiewicz, and J. W. Park Novel Nanoliposomal CPT-11 Infused by Convection-Enhanced Delivery in Intracranial Tumors: Pharmacology and Efficacy. Cancer Res., March 1, 2006; 66(5): 2801 - 2806. [Abstract] [Full Text] [PDF]

				R. A. Larson Acute Lymphoblastic Leukemia: Older Patients and Newer Drugs Hematology, January 1, 2005; 2005(1): 131 - 136. [Abstract] [Full Text] [PDF]

				T. M. Allen and P. R. Cullis Drug Delivery Systems: Entering the Mainstream Science, March 19, 2004; 303(5665): 1818 - 1822. [Abstract] [Full Text] [PDF]

				P. Sapra, E. H. Moase, J. Ma, and T. M. Allen Improved Therapeutic Responses in a Xenograft Model of Human B Lymphoma (Namalwa) for Liposomal Vincristine versus Liposomal Doxorubicin Targeted via Anti-CD19 IgG2a or Fab' Fragments Clin. Cancer Res., February 1, 2004; 10(3): 1100 - 1111. [Abstract] [Full Text] [PDF]

				D. F.S. Kehrer, A. M. Bos, J. Verweij, H. J. Groen, W. J. Loos, A. Sparreboom, M. J.A. de Jonge, M. Hamilton, T. Cameron, and E. G.E. de Vries Phase I and Pharmacologic Study of Liposomal Lurtotecan, NX 211: Urinary Excretion Predicts Hematologic Toxicity J. Clin. Oncol., March 1, 2002; 20(5): 1222 - 1231. [Abstract] [Full Text] [PDF]

				D. C. Drummond, O. Meyer, K. Hong, D. B. Kirpotin, and D. Papahadjopoulos Optimizing Liposomes for Delivery of Chemotherapeutic Agents to Solid Tumors Pharmacol. Rev., December 1, 1999; 51(4): 691 - 744. [Abstract] [Full Text] [PDF]