Use of combination therapy with cisplatin and calcitriol in the treatment of Y-79 human retinoblastoma xenograft model

Br J Ophthalmol. 2009 Aug;93(8):1105-8. doi: 10.1136/bjo.2008.152843. Epub 2009 Mar 30.

Abstract

Background: Retinoblastoma is the most common primary malignant intraocular neoplasm of childhood. The poor outcomes of patients with metastatic retinoblastoma have encouraged the search for new therapies. In the current study, the efficacy of combination therapy with calcitriol and cisplatin in athymic mice with subcutaneous Y-79 human retinoblastoma tumours was assessed.

Methods: 60 athymic mice were subcutaneously injected with human Y79 retinoblastoma cells. Animals were randomised into four groups: group 1, 50 microg of cisplatin; group 2, 0.05 microg of calcitriol; group 3, 0.05 microg of calcitriol and 50 microg of cisplatin; group 4, control. The cisplatin was administered once a week, and the calcitriol was given five times a week.

Results: There was a significant inhibition of tumour growth in animals treated with the combination therapy of calcitriol and cisplatin as compared with controls and cisplatin alone (p = 0.0001 and p = 0.0041 respectively). In terms of toxicity, serum calcium levels were increased, but there was no mortality and minimal nephrotoxicity in any of the groups.

Conclusion: The present study shows that cisplatin given in combination with calcitriol may be a viable multidrug therapy option in the treatment of high-risk retinoblastoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Calcitriol / administration & dosage
  • Calcitriol / adverse effects
  • Calcium / blood
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Drug Administration Schedule
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Retinal Neoplasms / drug therapy*
  • Retinal Neoplasms / pathology
  • Retinoblastoma / drug therapy*
  • Retinoblastoma / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Calcitriol
  • Cisplatin
  • Calcium