Combination of vandetanib, radiotherapy, and irinotecan in the LoVo human colorectal cancer xenograft model.

Journal article

PURPOSE: The tumor growth kinetics of the human LoVo colorectal xenograft model was assessed in response to vandetanib, an orally available receptor tyrosine kinase inhibitor, radiotherapy (RT), or irinotecan (CPT-11), as single therapies and in combination. METHODS AND MATERIALS: LoVo cells were injected subcutaneously into the right hind limb (5 x 10(6) cells in 100 microL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm(3) before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3 x 3 Gy) on Days 1, 2, and 3. CPT-11 was given at 15 mg/kg intraperitoneally on Days 1 and 3. Tumor volumes were measured on a daily basis and calculated by measuring tumor diameters with digital calipers in two orthogonal dimensions. RESULTS: All three single treatments (vandetanib, CPT-11, and radiation) significantly slowed LoVo colorectal tumor growth. Vandetanib significantly increased the antitumor effects of CPT-11 and radiation when given in combination with either of these treatments. These treatment combinations resulted in a slow tumor growth rate during the 2 weeks of vandetanib administration. The triple combination of vandetanib, CPT-11, and radiation produced the most marked improvement in response as observed by measurable shrinkage of tumors during the first week of treatment. CONCLUSIONS: The tumor growth delay kinetics observed in this study of the LoVo colorectal model suggest concurrent and sustained post-sequencing of vandetanib with cytotoxic therapy may be beneficial in tumors of this type.

Authors: Wachsberger, P; Burd, R; Ryan, A; Daskalakis, C; Dicker, A

• Publication status: Published
• Journal: International journal of radiation oncology, biology, physics
• Volume: 75
• Issue: 3
• Pages: 854-861
• Publication date: 2009-11-01
• DOI: 10.1016/j.ijrobp.2009.06.016
• EISSN: 1879-355X
• ISSN: 0360-3016
• Language: English
• Keywords: Animals; Angiogenesis Inhibitors; Protein Kinase Inhibitors; Combined Modality Therapy; Camptothecin; Mice; Dose Fractionation; Piperidines; Antineoplastic Agents, Phytogenic; Quinazolines; Humans; Xenograft Model Antitumor Assays; Tumor Burden; Receptor, Epidermal Growth Factor; Colorectal Neoplasms; Mice, Nude