Irradiation Modulates the Pharmacokinetics of Anticancer Drugs for Head and Neck Cancer

The concurrent use of chemotherapy during radiation therapy (CCRT) is now the important treatment stratagem for locally advanced head and neck cancer or nasopharyngeal cancer (NPC). For these cases, 5-Fluorouracil (5-FU) and cisplatin (CDDP) are the most commonly used agents of CCRT. It plays an important role to improve the treatment outcome and increases the opportunities for organ preservation. In the past, Radiotherapy (RT) was solely used as a local treatment and its effect was estimated by local effect model. However, growing evidence shows that irradiation has direct DNA damage-dependent effects as well as sending signals to neighboring cells. Recently, the investigators reported that abdominal irradiation could significantly modulate the systemic pharmacokinetics of 5-FU at 0.5 Gy, off-target area in clinical practice, and at 2 Gy, the daily treatment dose for target treatment in an experimental rat model. Additionally, the results from a clinical investigation showed that colorectal cancer patients with lower AUC of 5-FU during adjuvant chemotherapy had lower disease-free survival. Taken together, these lines of evidence support the importance and necessity to search for the mediators responsible for the unexpected effect of local RT on systemic pharmacokinetics of chemotherapeutic agents, such as 5-FU. In the present study, the investigators examined whether the phenomena and mechanism of RT-PK(pharmacokinetics) is a fact for different anticancer drugs and for different part in human.