Abstract #2315: Tumor chemoradiotherapy and tissue toxicity assessment

Chemoradiotherapy is a standard treatment for locally advanced pancreatic cancer. Available data support the concept that current chemotherapeutic regimens do not substantially sensitize tumors to radiation therapy. Clinical data have shown that newer agents are superior to older agents for advanced pancreatic cancer. Therefore, we investigated the effects of the combination of these agents with radiation on a pancreatic cancer model, with special emphasis on the likelihood of sensitization of normal tissues contributing to increased toxicity. We established MiaPaCa pancreatic cancer xenograft tumors on the right thighs of nude mice and randomized them into four groups treated with vehicle, radiosensitizer, gamma-radiation (2Gy x 5 to the tumor alone), and gamma-radiation in combination with radiosensitizer. Bidimensional tumor measurements were made periodically after treatment and the time to doubling of tumor volume was estimated in each cohort. Tumors, both femurs and both thigh musculatures were collected from mice in each cohort and subject to X-ray densitometric analysis and immunohistochemical analysis. Changes in the bone density resulting from radiation are routinely determined from 2D radiographic images obtained using a commercially available imaging system, KODAK in-Vivo Multispectral FX system and the bone density analysis software. An ideal radiosensitizer widens the therapeutic window for treatment of locally advanced pancreatic cancer by improving the radioresponse of tumors without increasing normal tissue toxicity. Such agents need to be tested in animal models where simultaneous assessment of tumor and normal tissue effects are feasible. We present early evidence of such a radiosensitizer. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2315.