The first 2 authors contributed equally to this article.
Subconjunctival carboplatin and systemic topotecan treatment in preclinical models of retinoblastoma†
Version of Record online: 3 SEP 2010
Copyright © 2010 American Cancer Society
Volume 117, Issue 2, pages 421–434, 15 January 2011
How to Cite
Nemeth, K. M., Federico, S., Carcaboso, A. M., Shen, Y., Schaiquevich, P., Zhang, J., Egorin, M., Stewart, C. and Dyer, M. A. (2011), Subconjunctival carboplatin and systemic topotecan treatment in preclinical models of retinoblastoma. Cancer, 117: 421–434. doi: 10.1002/cncr.25574
The St. Jude Animal Imaging Center contributed to the imaging studies and surgeries.
- Issue online: 5 JAN 2011
- Version of Record online: 3 SEP 2010
- Manuscript Accepted: 4 JUN 2010
- Manuscript Revised: 18 MAY 2010
- Manuscript Received: 28 JAN 2010
- translational research
The authors demonstrated previously that the combination of topotecan (TPT) and carboplatin (CBP) was more effective than current chemotherapeutic combinations used to treat retinoblastoma in an orthotopic xenograft model. However, systemic coadministration of these agents is not ideal, because both agents cause dose-limiting myelosuppression in children.
To overcome the toxicity associated with systemic TPT and CBP, the authors explored subconjunctival delivery of TPT or CBP in an orthotopic xenograft model and in a genetic mouse model of retinoblastoma (Chx10-Cre;Rblox/lox;p107−/−;p53lox/lox). The effects of combined subconjunctival CBP (CBPsubcon) and systemic TPT (TPTsyst) were compared with the effects of combined TPTsubcon and CBPsyst. at clinically relevant dosages.
Pharmacokinetic and tumor-response studies, including analyses of ocular and hematopoietic toxicity, revealed that CBPsubcon/TPTsyst was more effective and had fewer side effects than TPTsubcon/CBPsyst.
For the first time, retinoblastoma was ablated and long-term vision was preserved in a mouse model by using a clinically relevant chemotherapy regimen. These results eventually may be translated into a clinical trial for children with this debilitating cancer. Cancer 2011. © 2010 American Cancer Society.