Abstract 3435: VEGF or VEGF and EGF receptor signaling inhibition by cediranib or vandetanib enhances the therapeutic effects of chemoradiation in an orthotopic small cell lung cancer model

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.3435-3435
• Main Authors: Hosho, Keiko, Komaki, Ritsuko, Tailor, Ramesh C., Ryan, Anderson, Jürgensmeier, Juliane M., Smith, Paul D., Jacoby, Joerg J., Takahashi, Osamu, Korshunova, Maria V., Erez, Baruch, Herbst, Roy S., O'Reilly, Michael S.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-3435

Background: Small cell lung cancer (SCLC) is associated with a poor prognosis and can recur even after chemoradiation therapy. In the current study, we evaluated the therapeutic, antiangiogenic, and radiosensitizing effects of cediranib (RECENTINTM; AZD2171), an orally available inhibitor of all 3 VEGF receptors, and vandetanib (ZACTIMATM; ZD6474), an orally available inhibitor of VEGFR and EGFR, in an orthotopic model of human SCLC that mimics patterns of SCLC progression. Methods: NCI-H187 human SCLC cells were injected into the left lungs of nude mice. To confirm tumor growth, 5 mice were sacrificed after 14 days. All had visible lung tumors and the remaining mice were randomized (8/group) to treatment with vehicle (control), cediranib (3 mg/kg/day po), vandetanib (25 mg/kg/day po), doublet chemotherapy (CDDP 8 mg/kg and CPT-11 15 mg/kg, weekly ip), radiation to the left lung and mediastinum (20 Gy in 5 fractions over 2 weeks), or vandetanib or cediranib in combination with radiation and/or chemotherapy. After 45 days, when controls showed signs of becoming moribund, all mice were sacrificed and assessed for lung tumor growth and metastasis. Lung tumors and adjacent tissues were analyzed by immunohistochemistry. Results: Treatment with vandetanib, cediranib, chemotherapy, or radiation inhibited lung tumor growth with a reduction in left lung weight by 56, 60, 87, or 86%, respectively, compared with control (P