Phase II Studies

Investigational New Drugs

, Volume 27, Issue 2, pp 159-165

First online:

A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in combination with irinotecan, 5-flurouracil, and leucovorin for metastatic colorectal cancer

  • Elaina M. GartnerAffiliated withWayne State University Email author 
  • , Kent A. GriffithAffiliated withThe University of Michigan
  • , Quintin PanAffiliated withThe University of Michigan
  • , George J. BrewerAffiliated withThe University of Michigan
  • , Gwen F. HenjaAffiliated withThe University of Michigan
  • , Sofia D. MerajverAffiliated withThe University of Michigan
  • , Mark M. ZalupskiAffiliated withThe University of Michigan

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Tetrathiomolybdate (TM) is an oral copper chelator under development as an anti-angiogenic agent. We evaluated TM in combination with irinotecan, 5-fluorouracil, and leucovorin (IFL). Serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor, interleukin 6 (IL-6), and IL-8 were measured to evaluate the anti-angiogenic effect. Twenty-four patients with metastatic colorectal cancer were treated. The combination with IFL was well tolerated and dose intensity of IFL was maintained during combination therapy with TM. By intention to treat analysis, the overall response rate (RR) was 25% (95% CI 9.8–46.7) and the median time to progression (TTP) was 5.6 months (95% CI 2.7–7.7). VEGF levels were correlated with TTP, as were changes in VEGF, IL-8, and IL-6. TM can be safely added to IFL without compromising dose intensity or diminishing the expected RR. Changes in serum VEGF, IL-8, and IL-6 after treatment may directly reflect changes in CRC tissue angiogenesis.


Colorectal cancer Anti-angiogenesis Tetrathiomolybdate Copper chelation Vascular endothelial growth factor