Everolimus (RAD) inhibits in vivo growth of murine squamous cell carcinoma (SCC VII).
OBJECTIVE
Everolimus (RAD) is an mTOR inhibitor closely related to rapamycin. A potent immunosuppressive agent, it has also shown evidence of antineoplastic properties. SCC VII is a spontaneously arising murine squamous cell carcinoma line. This study examines the effect of everolimus on SCC VII proliferation. The data may provide support for the use of everolimus in transplant recipients with a history of malignancy.


METHODS
A dose efficacy study was conducted that used a murine model of intradermal tumor growth and pulmonary metastases. The development of intradermal tumors and pulmonary metastases were studied. Of 80 total mice, 40 received intradermal injection of 1 x 10 SCC VII cells and 40 received intravenous injection of 1 x 10 cells to establish pulmonary metastases. Within each group, animals were subdivided into four subgroups that received 1) 1 mg/kg everolimus twice a day, 2) 0.5 mg/kg everolimus twice a day, 3) 7.5 mg/kg cyclosporine per day, and 4) no treatment. Intradermal tumors were measured three times per week. Animals receiving an intravenous tumor injection were killed after 17 days and pulmonary metastases were quantified. Medication trough levels were measured in all treated animals.


RESULTS
Everolimus showed statistically significant tumor inhibition at 1.0 mg/kg twice a day and 0.5 mg/kg twice a day when compared with animals treated with cyclosporine and with untreated animals (P < .0001). Tumor inhibition was evident in both models studied (intradermal tumors and pulmonary metastasis generation).


CONCLUSIONS
Everolimus provides potent tumor inhibition in animals inoculated with SCC VII cells. Inhibition of both local and distant spread of disease is evident. Although most immunosuppressives are known to potentiate neoplastic disease, this study supports the use of everolimus immunosuppression in the face of prior malignancy. This data has significant implication for laryngeal transplantation after laryngectomy.
Khariwala
Samir S
SS
Head and Neck Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Kjaergaard
Jorgen
J
Lorenz
Robert
R
Van Lente
Frederick
F
Shu
Suyu
S
Strome
Marshall
M
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068338:Everolimus; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus