GrouseMan wrote:The dosing schedule sounds similar to what my wife's current trial is attempting to do with Irinotecan, Erbitux, with or without Avastin (or placebo). They dropped the 5-FU from the previous FOLFIRI and added Erbitux. She thinks she is still getting the Avastin based on previous experience with it (She is still on the ACE inhibitor they use with Avastin use though her BP is usually low to begin with). She has only the infusion on Mondays, then nothing again until day 14 when she gets hit again. Problem is I don't know if they are using a higher dosage of Erbitux or not. She is tolerating this very well and the rash came on after a week, not right away, but she thinks it was subsiding prior to yesterdays infusion (which was #2).
I am of course interested in the UCSD trial as I contributed research to these class of drugs - particularly CI-1033, and Dacomitinib. I still believe despite the failure of Dacomitinib against Erlotinib in the big Pfizer NSCLC trial (ARCHER 1009) that Dacomitinib is still a superior EGFR family inhibitor. The UCSD trial looks promising. We know that EGFr inhibitors once they become resistant, that if one lays off them for a while the pathway that was diverted and make the tumors resistant will revert and EGFr inhibitors become effective again. So I wonder also if this dosing schedule and concentration used in the trial isn't working similarly. Hitting the tumor hard, relaxing, and not enabling the tumor to slide into the alternative signaling pathway. Many questions that hopefully this trial will answer. I wonder if they would consider using Dacomitinib in an arm of the crowd funded trial also?
Good points and questions GrouseMan, thanks-
First of all, I wish you wife good results on her trial!
In terms of your points;
- I think a mechanistic goal of delaying resistance via pulse dosing is very much on their minds.
- You raise an interesting question re: Dacomitinib. The final trial protocol has not been written yet - I will discuss it with the PI!
- I think they are intentionally focusing on using a LMW EGFR inhibitor to have a better dosing controlled PK (cetuximab's PK is quite variable between people and can have a very long half-life).
I am a big fan of alternative dose schedules in general when there is a strong scientific basis to try.
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/2016 Colondar 2.0 ModelDK37 Science Posts List