Prof. dr. Siegfried Segaert, I was thinking of a question about your medical progress in the last years - what can you say about it?
The medical progress for treating cutaneous side effects of the EGFR-inhibitors. The main progress has been that quite some trials have been performed, especially with tetracyclines, for the treatment of the side effects of the skin and mainly the question that was addressed was whether we should treat prophyilactically or in the reactive way.
So, prophylactically means that we start treating using EGFR-inhibitors and let’s say that not all the trials go in the same direction, but there is certainly an overload of trials showing that a prophyilactic approach does better than a reactive approach (especially the STEPP trial - „Skin Toxicity Evaluation Protocol with Panitumumab” - shows so), and I think that every patient deserves the general measures- and that means sun protection, trying to stay out of the sun, but also using sun-blocking creams, UVA, UVB, with the factor of at least 20-30, every 2 to 3 hours, using an emollient cream - which one the patient likes, which is nice, which smells good, otherwise the patient will not use -, also to take measures like not to dry out the skin - so when the patient is washing, first advise for using water that is not too hot, second - not to frequently, third - not too long in the shower, and fourth - to use a shower oil; and then, regarding the use of the tetracyclines, either you start treatment already at the same time, so with the prophylactic approach, I think this is ok, and most of the trials showed that there are advantages, but not all the trials showed this, and I think that also an early reactive approach from the first appearance of the lesions - that’s another way of treatment.
All trials have shown that when you wait for too long, until you have an established acneiform eruption, you are too late. So, either you do it prophylactic, or early reactive.
For the topical treatments, I think topical antibiotics, especially metronidazole, does very well, and the reason for this is that it works well and is also very mild for the skin.
These patients have a very sensitive skin and the skin burns already, being very irritable, so they need treatments which do not irritate, and this metronidazole cream is normally meant for rosacea patients, who also have a very sensitive skin and it works very well for them.
So, topical corticosteroids are effective, but I would not recommend them for mild to moderate reactions, not because they aren’t effective - they are effective but they may induce acne or rosacea by themselves, which are very hard to treat. So, I would keep them just for the third grade reactions, and then to use a steroid like fluticasone propionate for a short period of time until the third grade reaction goes back in second grade. Because in this way, you will not have the bad side effects of the steroid itself.
How do you manage skin toxicity related to EGFR-inhibitors?
In fact, that’s what I’ve just said, all the general measures: sun protection, using emollient creams and the patients should use shower oil, water not too hot; for mild reactions - metronidazole cream; for moderate reactions - metronidazole cream plus minocycline 100 mg per day; in the severe reactions - metronidazole cream plus minocycline double dose, twice 100 mg per day, and for those patients who are not responding, you could add the fluticasone propionate steroid cream for a short time. You also need to be aware of suprainfections, so when the lesions get oozing or crusty, so when they get wet, take a swab and add cefuroxime for 5 days, and then it looks very well for the suprainfection.
OK, how involved are pharmaceutical companies as Amgen in the management of skin adverse reactions of EGFR-inhibitors?
I think they are very involved, because they organize educational events in which dermatologists like myself can teach how to treat these reactions, but also they make brochures on how to treat and how to recognize, how to treat and organize clinical trials like STEPP, and they are also doing lots of efforts to make like packages - that contain products which can be used in the prophylactic way.
What’s your opinion about the medical research field of dermatology and oncology here in Romania?
When it’s up to the side effects of the target therapies, I think that in comparison to the clinical trials looking at the effectiveness, there is still lots of need for new clinical trials looking at supportive treatment, and I think, well, there’s maybe a ratio of 1 to 20, or 1 to 50, so I think it could be improved, and I think that sometimes pharmaceutical companies, but also authorities, underestimate the impact that side effects may have on the patients, especially cutaneous side effects which are in visible areas - when they are full of pimples, patients do not want to go out, they want to stop the drug, which is bad for the cancer, so I think that is a dramatic impact on the treatment of the patient, but also on the good use of resources for medicine, and I think that I would plead for some more interest, and that new trials and new research should be initiated. So, everything can be better, it’s true there have been some nice trials in the last few years but we should not stop here. I think the effort should be continued.