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Context Treating patients with metastatic carcinoma of the pancreas can lead to regression of disease, but the tumor becomes resistant to therapy within a few months. If resistance can be reversed or prevented, the chemotherapeutic benefit may be prolonged. Case reports Two patients with metastatic pancreatic cancer progressed on gemcitabine, capecitabine and docetaxel (GTX). When sirolimus was added to this regimen at a dosage to achieve a serum level of at least 10 ng/dL at the time of the gemcitabine and docetaxel infusion, their tumors regressed. Conclusion This demonstrates that the addition of sirolimus to a gemcitabine/docetaxel containing regimen can reverse tumor resistance in the clinical setting.