Gastrointestinal Cancer

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SU_13_2132 - Liver stereotactic body radiation therapy modulates systemic pharmacokinetics of sorafenib through p-glycoprotein

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Liver stereotactic body radiation therapy modulates systemic pharmacokinetics of sorafenib through p-glycoprotein
C. H. Hsieh1,2, Y. J. Chen3,4, T. H. Tsai5, and L. Y. Wang6; 1Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, 2Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, Taipei, Taiwan, 3Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan, 4Department of Medicine, MacKay Medical College, New Taipei City, Taiwan, 5Institute of Traditional Medicine, National Yang-Ming University, Taiwan, Taiwan, 6National Taiwan University, Taipei, Taiwan

Purpose/Objective(s): Sorafenib improves survival for patients with hepatocellular carcinoma (HCC). The efficacy of stereotactic body radiation therapy (SBRT) concurrent or sequential with sorafenib in unresectable HCC patients is better than single agent. However, it is unclear where the concentration of sorafenib in the plasma can be modulated by SBRT or not. Here, we evaluate the influence of liver SBRT on the pharmacokinetics (PK) of sorafenib by free-moving rat model.

Materials/Methods: Free-moving Sprague-Dawley rat model was used in the current study. Image-guided SBRT with 9 Gy was delivered to the liver with field size 1.5 x 1.5 cm. The experimental animals were randomized to (A) the sorafenib-only (40 mg/kg, p.o.) group and (B) pre-treated with cyclosporin A [CsA, p-glycoprotein (p-gp) inhibitor, 20mg/kg, i.p. 30 min before RT] group. In each group, the experimental animals were randomized to sham SBRT (0 Gy with sorafnib), concurrent (after SBRT9Gy 1 hour) and sequential group (after SBRT9Gy 24 hour), respectively. The PK of sorafenib in the plasma system was calculated. Each group’s data was collected from six rats

Results: For sorafenib-only group, compared to the sham-irradiated controls, the area under the concentration versus time curve (AUC) of sorafenib (40 mg/kg) was increased 263% in concurrent group (720 versus 1891 min*ug/mL, p = 0.038). Additionally, the AUC of sorafenib was also increased by 202% in sequential group (720 versus 1457 min*ug/mL, p = 0.018). Compared to the SBRT9Gy 1 hour plus sorafenib without pretreated with P-gp inhibitor, the AUC of sorafenib in the pre-treated with CsA was decreased by 213% (604 vs. 1891 min*ug/mL, p = 0.028). Interestingly, the AUC of sorafenib in the sequential group pre-treated with CsA was decreased by 89% (772 vs. 1456 min*ug/mL, p = 0.037).

Conclusion: Liver SBRT modulates the PK of sorafenib that was proved by rodent model. Additionally, p-gp plays an important role during the RT-PK phenomena of sorafenib. The strategy for modulating the RT-PK phenomenon of sorafenib through p-gp is worth to investigate in the future.

Author Disclosure: C. Hsieh: None. Y. Chen: None.

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