EFUDEX --------------------------------------------------------- I would like start a thread on Efudex . The motivation is a number of patients i have seen who have had 2 weeks courses of Efudex and I am unimpressed with the results of this regimen. I would like to hear from the group and would two issues addresed: 1. Is a two course of Efudex 5% adequate therapy for diffuse thick AKs? 2. How do you use Efudex? To show my own bias, I admit that I am a lover of Efudex for diffuse AKs and for "cleaning up" all those foci of atypia that many of my patients waiting to convert to their next tumor and have found the approach that is most effective as follows: GENERAL, for diffuse AKs. No overly hyperkertotic lesions; no immunosuppression. Face: 5% cream b.i.d x 30 days. Miss a dose, increase treatment duration by one day. Scalp: 5% soution (or 5% cream if bald) b.i.d x 45-60 days. Miss a dose, increase treatment duration by one day. Arms: 5% cream b.i.d x 60-90 days. Miss a dose, increase treatment duration by one day. Longer courses for transplant patients, who I will often treat until healed despite continued treatment. All patients are given an Efudex info booklet, told how miserable they will be, told alternatives (chemical peels, laser resurfacing, dermabrasion, Retin-A, alpha hydroxy acid products), told to come any time it gets intolerable (and if they do get Atarax the first time, Ambien the second and rarely narcotics). I do not like to turn off the inflammation with topical or systemic, 'roids as I have noted (yes, only my couple of hundred anecdotes) that these patients seem to have have less complete responses from the perspectie of AK elimination. I will occasionally use pulse regimens (5% cream b.i.d.) 2-3 days in a row out of seven on patients who will not do a full course, but find it less effective for AKs but useful on HPV positive SCCa of digits and genitals an d condyloma patients who have a history of many recurrences to suppress new lesion development. I also use it on warts (liquid dotted on to planar warts; liquid applied to warts just about anywhere). Daniel Mark Siegel MD, MS ------------------------- I hate efudex. Patients look like they're napalmed, hurt like crazy and call me on the phone too much. In a year or two they need it again. I wouldn't use it myself if I had lots of AKs. Having said that, I do use it in a few selected patients; typically those with a zillion lesions. I have them apply it for three days each week, which doesn't usually make too much of a mess. After 2 or 3 months most of the AKs are gone. Guy Webster ----------- Re: >>1. Is a two week course of Efudex 5% adequate therapy for diffuse thick AKs? Not in most cases. Re: >>2. How do you use Efudex? Generally I prescribe 5% Efudex Cream to be applied b.i.d. for about 3 weeks dependent upon the patient's response to therapy. The endpoint seems to be when most lesions have become erythematous patches, some of which are superficially eroded (or when the patient says "enough is enough", which generally occurs around the 2 to 3 week point). I usually recommend bland emollients and/or antihistamines for symptomatic relief. I have used "pulsed" therapy with great success in many patients who did not want to become hermits for a month. I generally have them apply the Efudex b.i.d. on two consecutive days of each week. I have had occasional patients who could tolerate Efudex applied on only one day per week and have even seen good results with this regimen. Using these "pulsed" regimens, I find that a good response often can be achieved in 9 to 12 weeks of treatment. John F. Kaiser, MD ------------------- A few years ago someone published Efudex on weekends with good results - and it does work well. This is the only way I Rx Efudex - its slower, but a whole lot easier to tolerate. Shoot a photo before starting - this will help yourself and your patient appreciate that progress is happening. Important to tell them to put the cream EVERYWHERE, not just on the spots. I have some patients (eg. transplant) on Efudex on weekends for life. Sometimes I'll hit the thicker AKs with LN2, or even currettage. (I hear that in some places these might be read out as a "California squame" and treated with MOHS surgery, and maybe a flap or a graft, just for good measure.) I've used Efudex with 20% sal acid with some success for warts, and I tried mixing 5FU powder with DuoFilm, but just made a mess of the kitchen! I think it would be easy to use and very effective if it could be compounded properly. KC Smith MD FRCPC ------------------ I have several patient with extreme cases of sun damage who use the 5 fluorouracil directly on AK's of the face and scalp when they crop up (BID x until the lesion disappears). These patients are the type with severe total body disease who would have thousands of AK's, BCC's, SCC's and Keratoacanthomas. I find that these challenged patients can achieve great control with only local irritation. A retired professor of pharmacology at Yale who worked diligently towards understanding the mechanism of action of 5-FU for 25 years told me after using 5FU to treat his AK's that he believed it worked by triggering inflammation. We had isolated the receptor for cyclosporin A together 10 years earlier. Rhett Drugge, M.D. ------------------ I have used Efudex bid for 4-6 wks for the past seven years for both superficial multicentric BCC's and Bowen's Dz, as discussed by Klaus Goette in the "J Assn of Military Dermatologists", Vol. XV, No. 1, 1989. All lesions have cleared and no recurrences to date. Concern has been expressed about hair follicles in Bowen's, but with careful f/u, that hasn't emerged as a problem. I also use 5-FU, 2% in 99% pyruvic acid for warts. Apply saturated cotton or gauze pledget, tape, and instruct pt to remove in 8 hrs. Pain varies from none to calling back and requesting T3. Dan Mitchell, MD ---------------- I know this is unforgiveable scientifically, but John Knox and the other faculty at Baylor forcefully imparted to me their dislike for Efudex, so I have never used it. One of their points was that incompletion of the course could cause normal epithelium to overgrow squamous carcinomas, delaying the diagnosis. I have no idea whether any of this is, in fact, true, but I have seen numerous patients over the years who had used Efudex, were miserable from it, and were looking for any other alternative. I suggest freezing the worst AK's, waiting a month to see if any fail to respond (biopsying those which don't), then doing a couple of combo glycolic/TCA peels about three months apart. Much less uncomfortable than the Efudex. Jay McCarty ----------- The Scandinavians up here in Wisconsin must be made of different stuff. I give people Efudex all of the time, to use to limitted areas (forehead for example) . They actually return or call the following year to treat the next segment. Judges, ministers, state legislators........And, several years later these areas still look gorgeous. By the way, I usually try to disuade them first. Maybe they see it as a challenge? There was a recent study revealing that people who had efudex on one side, chemical peel on the other, had the same degree of clearing but were happier with the shorter period of peel side effects. Diane Thaler ------------ I use topoical fluorouracil for the following: 1. willing patients at the VA 2. actinic keratoses previously treated with LN2 (and lacking signs of induration or tenderness to suggest SCC) 3. large actinic keratoses on prominent areas I tell patients not to tell anyone who asks what happened to their face who their dr. is, and that they will look terrible. I await meaningful evidence that fluorouracil treats only the surface, allowing an SCC to grow. Even if this happened, which I doubt, I wonder exactly what the risk would be. Barbara R. Reed, MD ------------------- I use topical 5fu for diagnosis as well. Some people get very concerned about every little "spot"-I tell them to rub it on for 2-4 weeks to see if it gets irritated. Also, I show people the pictures of the spared skin, so they can differentiate a full blown contact from the spotty inflammation. In response to someone who wrote in about not using it at all, and it just being an irritant, I doubt that is how it works iv in ca. Rumor had it that its usefullness in AKs was discovered when a woman with breast ca was given 5fu iv and all of her AKs lit up. Maybe Mark Ling knows the mechanism and more accurate story of its origins. Diane Thaler I feel there is definitely a geographical response difference to Efudex. When I used it on patients in Michigan during residency there was usually a mild to moderate responce with little erythema in nonlesional skin. After practicing in Florida for many years I have come to appreciate the considerable increase in inflammation and irritation from Efudex, especially on nonlesional skin. So I think if we would move some of those Wisconsin Swedish folks to Florida and expose them to thousands of hours of our intense sun, they would be uncomfortable with Efudex. I grew up in Wisconsin and was very appreciative of summer-loved both days! It's interesting that in my area, the Plastic Surgeons use Efudex a lot more than Derms- often use it to "check their margins". Hal Rehbein Maybe the heat here in Texas makes the patients more uncomfortable with the Efudex? We do see many more neglected cases of AK's and skin cancers in the summer. They tolerate the lesions in the winter, but the heat makes them unbearable, so they come in. Jay McCarty ----------- I really can't believe we're having this discussion about the usefulness of 5-FU. Having used it regularly for 28 years, I think it's the hands down winner for the patient who has "many early lesions." Certainly it beats a wholesale attack with the Cry-ac. Mike Eichwald -------------- I have had patients on systemic 5FU for colonic cancer. I have seen no response in such patients. The suggestion that 5FU worked by triggering inflammation came from the former chairman of the department of pharmacology at Yale who had been studying 5FU's pharmacology for several decades. Of course, as in psoriasis, it may be difficult to identify drug mechanisms of action in dermatologic diseases. Until the immunologic basis of psoriasis became better understood, it was common knowledge that methotrexate worked by direct inhibition of keratinocyte proliferation. Now perhaps we may believe that its effectiveness is via T cell inhibition. Rhett Drugge, M.D. ------------------ I recall from biochem in pre-med that most metabolic reaction rates double with each 10 degree Centigrade rise in temperature, so an increase of even a few degrees in the skin surface temperature (eg. FL or TX vs. MI or WI) could account for the more florid response to 5-FU in warmer climates, and at warmer times of year. KC Smith MD FRCPC Maybe this is why I only treat in the Fall or Winter. Diane Thaler I have twice seen what I strongly felt was the phenomenon of actinics lighting up with IV 5-FU. Once in a man with colon ca and once in a woman with breast ca. Each time they were referred by their onc to R/O allergic reactions to meds. Sites of involvement were certainly those of AKs. I cannot recall time of year they were seen. Photo reaction of some type might be in the differential. Jerry Eisner ------------ Diane Thaler suggested that the origin of use or 5-fluorouracil for AKS was the emergence of actinic keratoses during treatment of breast cancer with the drug. I have seen a similar case, a hospital consult for drug rash which turned out to be DSAP lesions which emerged during chemotherapy with 5FU. I also agree with use of the drug for diagnostic treatment, as Diane suggested. Barbara R. Reed, MD ------------------- Since everyone is giving Efudex stories,this is a true one that I experienced. An elderly man had been given Efudex by another M.D. some years earlier. When he developed symptoms of "jock itch" he searched his medicine cabinet and,forgetting what it was for, found the Efudex and applied it. It was not a pretty sight! He avoided going in the hospital, but it was close! It took almost 2 weeks to regrow the skin. Hal Rehbein Barbara, have you had luck with topical 5Fu for DSAP. Diane Thaler ------------ I have treated two patients with DSAP using Efudex 5% cream. Had the expected inflammatory reaction, and certainly "lessened the load" of lesions to the point that the patients were satisfied. Also, I remember one patient with Porokeratosis of Mibelli on his heel that responded to 5-FU, but we had to get vials of the injectable agent, which he applied directly to the lesion, and then occluded. This alternated with occasional Keralyt (when it was available). He tolerated it well and now, 10 years later, there is no sign of recurrence. Scott Clark -----------