Tuesday, June 16, 2009

Fenretinide (4-HPR) Complete Responses

The 2009 ASCO Annual Meeting was at the beginning of June this year and there were some relatively exciting findings. The great thing about the ASCO meetings is that they publish their meetings online and often you can even find video and/or audio of many of the oral and keynote presentations. There were a couple of interesting findings to come out of the world of neuroblastoma research at this year's meeting. Most notable, of course, was the reporting of the phase 3 study results of the ch 14.18 antibody that I have talked about so much before. However, there were some other exciting findings as well. One finding that I was happy to see published out there in the real world where everyone could see it was the result of the Phase 1 study of Fenretinide (4-HPR) oral powder in patients with recurrent and/or resistant neuroblastoma.

If I am being honest, I actually feel a tinge of vindication concerning these results. For years, I have told other parents about the low toxicity and promise of this drug. Sadly, several other parents who did not understand the nature of phase 1 trials actively lobbied against this trial and drug. Many times they went as far as to tell other parents not to let their child participate in this trial. While their comments certainly had the effect of slowing down the trial, decreasing participation, and probably costing some kids a good chance at response; it did finally close. I am even happier to see the amount of complete responses. I often explained that the major challenge with this drug was getting enough of it into kiddos. There were many barriers. However, new formulations, such as this one, held much promise. In the end, this trial produced 4 complete responses out of 15 patients for dose levels 4 through 8. The other important thing to note is that the patients that responded all responded once the drug was able to get to efficacious dose levels - yes, the very nature of a phase 1 trial.

So 4 out of 15 in a phase 1 trial is an incredible response. Keep in mind, I said COMPLETE responses - not partial , not mixed, but genuine complete responses in neuroblastoma. This is better than many drugs that I have seen in a long time. However, it is not time to run out and fill your child up with 4-HPR. Like any other drug their are types of disease that it works best on and types of disease in which it is virtually useless. Furthermore, it is not very good for progressive disease. However, it is good for marrow disease and, to a lesser extent bony disease. Finally, it is still only available to patients with relapsed disease. So, if you fit these criteria it is certainly an option that you should be discussing with your physician, or bettter yet a neuroblastoma medical expert.

The abstract about this trial can be found here:

Sometimes purpose can really feel validating.


Anonymous said...

Just wondering where you found "4 complete responses out of 15 patients in a phase 1 trial." According to the ASCO abstract, the trial accrued 32 patients, 30 of whom were evaluable for response. That would make the response rate ~13%, not ~26%

Mark Dungan said...

The statement is from the conclusion of the trial. "4-HPR/LXS oral powder was well tolerated, obtained 2 - 5 fold higher 4HPR plasma levels than fenretinide capsules on the same dose and schedule (P < 0.01), and showed anti-tumor activity (complete responses in 4/15 patients at DL4-8)."

I think the miscommunication is regarding which patients they were evaluating. They were looking at the 15 patients in dose levels 4 - 8. Regardless, this is an excellent response rate for such a non toxic agent. In fact, I can not think of any other agent that has produced such results in neuroblastoma with as little toxicity.