Rashes from EGFR inhibitors: we like to see them, because we know that many trials have shown that skin toxicity on drugs like tarceva is associated with better survival (see prior post), but the fact is that sometimes a rash is more than an inconvenience and can really make people miserable, or at least pretty unhappy, as described in the comments and questions from a discussion forum thread today. I've described some general management principles for rash in another prior post, but in truth, oncologists aren't well trained in rash management, and we've generally had to learn as we go along, because EGFR inhibitors have introduced this as a new problem in oncology. Tarceva is a well established treatment at this point for lung cancer, and while the monoclonal antibody Erbitux has been used primarily in colon cancer and head and neck cancer thus far, a major lung cancer trial with erbitux was also recently reported as positive (post here), so there's a strong possibility that erbitux, which is also associated with very significant rashes (and better survival correlated with that), will also be used increasingly for lung cancer.

But there may be more to managing these rashes than the basics I described in prior posts. One of the leading experts is Dr. Mario Lacouture, a dermatologist from Northwestern Univ., who has published some proposed guidelines that are an alternative to some of the other approaches I had previously described (paper here, with a rather complex algorithm figure included). This work focuses on early and aggressive use of minocycline (synthetic tetracycline) and elidel cream, a treatment developed and approved for eczema. In truth, I haven't used this yet, but I've heard from some people who have that Elidel and this general approach can be very helpful.

Dr. Lacouture is included in a panel on a CME program that is available on the web, "The Conundrum of Rash in Management of EGFR Inhibitors", which includes a detailed and somewhat complex medical presentation (the target audience is doctors) but that also includes several accessible take-home points. It's available through that website as a 70+ minute streaming video program, or a podcast or MP3 audio file, or you just download the transcript. One thing that the program highlights, in addition to the point that "oncologists are bad dermatologists" (sad but true), is that there is also the ongoing question of whether and when to temporarily hold the EGFR inhibitor therapy and then drop to a lower level. In general, while we'd try to manage people on the highest dose feasible, these are treatments that have the potentially to be chronically helpful. Because of that, I do see it as a question of what is the lowest dose needed to get the desired effect. if someone is having trouble managing on 150 mg and has been stable for many months, I think it's appropriate to test whether they might feel FAR better on 100 mg and have just as stable disease, or an ongoing response. While we've seen that patients who develop a severe rash can do particularly well, there's no evidence I'm aware of that people who lowered the dose subsequently (and felt better) did any worse than those who continued to suffer at the highest dose they could tolerate with difficulty.

Overall, it's good to see that we're starting to see more dedicated study of these EGFR-based rashes, and to get more actual results from these experiences. I think we'll need to continue to balance between aggressively managing side effects and to learn whether we need to dose to the borders of tolerability or whether reducing dose to a more comfortable chronic solution is appropriate.