Investigational New Drugs

, Volume 30, Issue 2, pp 647–652

A phase I study of temsirolimus and metformin in advanced solid tumours

  • Mary J. MacKenzie
  • Scott Ernst
  • Craig Johnson
  • Eric Winquist
PHASE I STUDIES

DOI: 10.1007/s10637-010-9570-8

Cite this article as:
MacKenzie, M.J., Ernst, S., Johnson, C. et al. Invest New Drugs (2012) 30: 647. doi:10.1007/s10637-010-9570-8

Summary

The purpose of this phase I trial was to establish the maximum tolerated dose and define the dose-limiting toxicities of a combination of temsirolimus and metformin. Patients with advanced solid tumours who had exhausted standard treatment options were eligible. Treatment included weekly intravenous temsirolimus and daily oral metformin. Eleven patients were enrolled. Dose-limiting toxicities were observed in all patients at the initial dose level of 25 mg weekly of temsirolimus and metformin 500 mg po BID. At dose level -1, 2 of 8 patients experienced dose-limiting toxicities. Toxicities included grade 4 pneumonitis, persistent grade 3 fatigue, and thrombocytopenia requiring dose delays. The maximum tolerated dose (level -1) was 20 mg temsirolimus weekly and 500 mg po daily of metformin. One patient with head and neck cancer experienced a partial response. Five patients had stable disease including a patient with melanoma who had stable disease for 22 months.

Keywords

Temsirolimus Metformin mTOR AMPK Advanced solid tumours 

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Mary J. MacKenzie
    • 1
  • Scott Ernst
    • 1
  • Craig Johnson
    • 1
  • Eric Winquist
    • 1
  1. 1.London Health Sciences CentreLondonCanada