Pegylated liposome-encapsulated doxorubicin and cisplatin enhance the effect of radiotherapy in a tumor xenograft model

K. J. Harrington, G. Rowlinson-Busza, K. N. Syrigos, Richard Geoffrey Vile, P. S. Uster, A. M. Peters, J. S W Stewart

Research output: Contribution to journalArticle

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Abstract

Concomitant chemotherapy and radiotherapy (CCRT) has recently been shown to improve treatment outcome in a range of solid tumors. Pegylated liposomes have the potential to target drugs directly to tumors and may increase the efficacy and reduce the toxicity of CCRT by selectively delivering radiosensitizing agents to tumor, as opposed to normal, tissues. In these studies, we have assessed CCRT using pegylated liposome encapsulated doxorubicin (PLED) and pegylated liposome encapsulated cisplatin (PLEC) against KB head and neck cancer xenograft tumors in nude mice. The addition of low-dose (2 mg/kg) PLED (P < 0.001) and PLEC (P < 0.001) significantly increased the effect of 4.5 Gy, but not 9 Gy, single-fraction radiotherapy (SFRT). Both PLED and PLEC were significantly more effective than their unencapsulated counterparts in increasing the effect of SFRT. In addition, PLED (P < 0.001) and PLEC (P < 0.05) significantly increased the effect of fractionated radiotherapy (9 Gy in 3 fractions) in two different dosing schedules (2 mg/kg single dose or three sequential doses of 0.67 mg/kg). Unencapsulated diethylenetriaminepentaacetic acid and pegylated liposomal diethylenetriaminepentaacetic acid were used as controls to test the effect of the liposome vehicle and showed no interaction with 4.5 Gy or 9 Gy SFRT (P > 0.1). CCRT was well-tolerated, with no evidence of increased local or systemic toxicity, as compared with radiotherapy alone. This study is the first to demonstrate the value of pegylated liposomes as vehicles for the delivery of radiosensitizing drugs in CCRT strategies.

Original languageEnglish (US)
Pages (from-to)4939-4949
Number of pages11
JournalClinical Cancer Research
Volume6
Issue number12
StatePublished - 2000

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Heterografts
Liposomes
Doxorubicin
Cisplatin
Radiotherapy
Drug Therapy
Radiation-Sensitizing Agents
Neoplasms
Head and Neck Neoplasms
Nude Mice
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Harrington, K. J., Rowlinson-Busza, G., Syrigos, K. N., Vile, R. G., Uster, P. S., Peters, A. M., & Stewart, J. S. W. (2000). Pegylated liposome-encapsulated doxorubicin and cisplatin enhance the effect of radiotherapy in a tumor xenograft model. Clinical Cancer Research, 6(12), 4939-4949.

Pegylated liposome-encapsulated doxorubicin and cisplatin enhance the effect of radiotherapy in a tumor xenograft model. / Harrington, K. J.; Rowlinson-Busza, G.; Syrigos, K. N.; Vile, Richard Geoffrey; Uster, P. S.; Peters, A. M.; Stewart, J. S W.

In: Clinical Cancer Research, Vol. 6, No. 12, 2000, p. 4939-4949.

Research output: Contribution to journalArticle

Harrington, KJ, Rowlinson-Busza, G, Syrigos, KN, Vile, RG, Uster, PS, Peters, AM & Stewart, JSW 2000, 'Pegylated liposome-encapsulated doxorubicin and cisplatin enhance the effect of radiotherapy in a tumor xenograft model', Clinical Cancer Research, vol. 6, no. 12, pp. 4939-4949.
Harrington, K. J. ; Rowlinson-Busza, G. ; Syrigos, K. N. ; Vile, Richard Geoffrey ; Uster, P. S. ; Peters, A. M. ; Stewart, J. S W. / Pegylated liposome-encapsulated doxorubicin and cisplatin enhance the effect of radiotherapy in a tumor xenograft model. In: Clinical Cancer Research. 2000 ; Vol. 6, No. 12. pp. 4939-4949.
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