Investigational New Drugs

, Volume 32, Issue 4, pp 710–716 | Cite as

Phase I trial of everolimus, gemcitabine and cisplatin in patients with solid tumors

  • Brian A. CostelloEmail author
  • Mitesh J. Borad
  • Yingwei Qi
  • George P. Kim
  • Donald W. Northfelt
  • Charles Erlichman
  • Steven R. Alberts


Background A Phase I trial of the 2-drug regimen of everolimus plus gemcitabine (Cohort I) and the 3-drug regimen of everolimus plus gemcitabine and cisplatin (Cohort II) was performed to determine the maximally tolerated dose (MTD) of both combinations. An expansion cohort (Cohort III) of patients with cholangiocarcinoma or gallbladder carcinoma was treated at the MTD. Methods A standard 3 + 3 design dose escalation was used. Everolimus was given on Monday/Wednesday/Friday or daily depending upon the dose level. Gemcitabine and cisplatin were administered on days 1 and 8 of each 21 day cycle. Results Twelve patients were entered in Cohort I and 15 in Cohort II. The MTD for Cohort I was everolimus 5 mg on Monday/Wednesday/Friday and gemcitabine 800 mg/m2. For Cohort II, it was everolimus 5 mg on Monday/Wednesday/Friday, gemcitabine 600 mg/m2, and cisplatin 12.5 mg/m2. All DLTs in this study were hematologic. Complete responses (CR) were seen in a patient with primary peritoneal carcinoma and another with recurrent pancreatic cancer. Partial responses (PR) were seen in 3 patients: breast, ampullary carcinoma and pheochromocytoma. Of 10 patients enrolled in Cohort III, six patients had stable disease and 4 had progressive disease. Conclusions This Phase I clinical trial has demonstrated that these 2-drug and 3-drug combinations are generally well tolerated and safely administered. The main DLTs in both regimens were hematologic, specifically thrombocytopenia. The 3-drug combination can be considered as a platform for future studies in specific tumor types.


Phase I Everolimus Gemcitabine Cisplatin Cholangiocarcinoma Gallbladder cancer 


Conflict of Interest

Dr. Mitesh Borad has received grant funding from Novartis Pharmaceuticals for unrelated research. All other authors declare they have no conflict of interest


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Brian A. Costello
    • 1
    Email author
  • Mitesh J. Borad
    • 1
  • Yingwei Qi
    • 1
  • George P. Kim
    • 1
  • Donald W. Northfelt
    • 1
  • Charles Erlichman
    • 1
  • Steven R. Alberts
    • 1
  1. 1.Mayo Clinic Cancer CenterRochesterUSA

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