Efficacy and Comparative Effectiveness of Sirolimus (Rapamune) as an Anticancer Drug
2011
Objectives/Hypothesis—To evaluate antitumor efficacy of the generic mTOR inhibitor sirolimus in preclinical animal models of head and neck squamous cell carcinoma (HNSCC) and compare its effects with those of the patented analog Temsirolimus. Study Design—In vivo study. Methods—To develop xenograft established tumor model (ETM) of HNSCC, FaDu cells were injected subcutaneously into nude mice. When tumors reached 50–60mm 3 mice were randomized into 5 groups and treated daily i.p. with sirolimus at various doses for 5 days a week for 3 weeks. Tumor volumes were measured. The results were compared with historical data on Temsirolimus effects. In the minimal residual disease (MRD) model surgical wounds were created and FaDu cells implanted. After 72h, animals were randomized into two groups and were injected i.p. with 0 or 5 mg/kg sirolimus for 5 days a week for one month. Results—In the ETM, sirolimus significantly inhibited tumor growth (p<0.01) although there was no overall significant difference in tumor growth inhibition between sirolimus and Temsirolimus. In the MRD model, sirolimus significantly suppressed growth of tumors (p<0.001) and improved survival compared with controls (p<0.01). There was a significant decrease in pS6 expression, indicating mTOR inhibition. Conclusion—In this study we demonstrate that the generic mTOR inhibitor sirolimus shows potent antitumor activity in HNSCC and produces comparable effects to the patent drug Temsirolimus. Sirolimus has the potential of serving as an economic and comparative targeted agent to Temsirolimus in the treatment of HNSCC.
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