Rapa/Cancer/GF Paper Rebound effect in 3/12 non-GF and non-Keto patients

  • I’ve done a site wide search and have not been able to find this discussed.
  • I was reviewing “Phase 1 Studies of Sirolimus Alone or in Combination with Pharmacokinetic Modulators in Advance Cancer patients”
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410974/pdf/nihms604208.pdf
  • On page 14, there a figure that shows a rebound effect with Rapamycin.
  • According to the authors "paradoxically, in 6/12 subjects we observed a rebound effect on phospho-p70s6k where phorsphorylated protein levels exceeded baseline at later time points (including 28 days later)
  • Unfortunately, they don’t state explicitly what dose resulted in the rebound, but they do add that “we determined rebound was driven by the concentration of sirolimus”
  • What do you all make of this?
  • 6/12 with rebound; with 3/12 with levels above baseline at 28 days?
  • I realize these are small numbers and it is difficult to draw conclusions.
  • As an aside, did anyone notice that Cmax for the GF baseline 15 mg was greater than the Cmax for the GF baseline 20 mg (prior GF intervention); I wonder if this is due to patient variability or small sample size.