Treatment options for the papulopustular eruption of gefitinib

Journal of Drugs in Dermatology, Jan, 2007 by Frank C. Victor

Treatment Options for the Papulopustular Eruption of Gefitinib

Commentary on:

Treatment of gefitinib-associated folliculitis. Matheis P, et al. J Am Acad Dermatol. 2006;55:710-713.

Summary

The authors present a case series of 3 patients in regard to the treatment of folliculitis secondary to gefitinib. All patients had stage IV nonsmall cell lung cancer, recalcitrant to platinum-based and docetaxel chemotherapies, and were being treated with gefitinib at the time of presentation. Patient one was a 59-year-old Caucasian man who had developed a papulopustular eruption on the face, neck, and the upper back and chest 17 days after initiating treatment with gefitinib at a dose of 250 mg daily. The eruption was categorized as grade 2. Histologic assessment showed a suppurative folliculitis as well as a dense perifollicular infiltrate. Although Gram stain of the specimen revealed Gram-positive cocci, aerobic cultures were negative. Treatment of the eruption with twice-daily metronidazole 0.75% cream was initiated. After 2 weeks of treatment, near complete resolution was noted and a selenium sulfide 10% combined with sulfa 5% wash was then added. The patient was reported as being "pleased" with the regimen and continued on it while taking gefitinib. After one month, the patient was noted to have generalized xerosis and an eruption of the lower extremities consistent with eczema craquele. Resolution of this eruption was achieved with topical triamcinolone 0.1% compounded with Eucerin[R], being applied twice daily. After 7 months, gefitinib was discontinued secondary to progression of the patient's lung cancer.

Patient 2 was a 70-year-old Caucasian man who developed fissuring and xerosis of the nasolabial folds followed by a papulopustular eruption of the nose 9 days after initiating treatment with 250 mg of gefitinib daily. The eruption subsequently spread to involve other areas of the face, the scalp, ears, neck, and upper back and chest. The eruption was categorized as grade 2. A suppurative folliculitis with follicular hyperkeratosis was noted on histology. Cultures revealed no pathogens. The eruption was treated with a twice-daily application of metronidazole 0.75% gel, in addition to a cleansing lotion and gel. After 2 weeks, a minimal response was noted and a cyst on the back, which had been previously quiescent, was severely inflamed. Oral doxycycline at a dose of 100 mg twice daily was added to the treatment regimen. The eruption improved to a grade of 1 after 4 weeks of treatment, although during this time, the patient experienced generalized xerosis and was diagnosed with asteatotic eczema. This was treated with a twice-daily application of triamcinolone 0.1% compounded with Eucerin. The asteatotic eczema was noted to improve. After 2 months of gefitinib treatment, the lung cancer was found to have stabilized.

Patient three was a 42-year-old Caucasian man who experienced a pustular eruption of the back and chest 30 days after commencement of gefitinib 250 mg daily. Thirty days later, a papulopustular eruption was noted on the scalp, face, neck, and upper chest and back. The eruption was pruritic and was rated as grade 2. The patient was started on a twice-daily application of metronidazole 0.75% lotion. After 2 weeks, the eruption had spread to the patient's upper thighs. Oral minocycline at a dose of 100 mg twice daily was added and, after one month, the eruption decreased to a grade of 1. A "dramatic response" to gefitinib was noted regarding the patient's lung cancer.

Comment

The authors present a case series of 3 patients with stage IV nonsmall cell lung cancer who were being treated with gefitinib and subsequently experienced a pruritic, papulopustular eruption. As previously discussed, this eruption is common in patients taking EGFR inhibitors. As this eruption is a fairly new entity, standard treatment protocols have yet to be established and randomized, and controlled trials regarding treatment efficacy are lacking. Topical and oral antibiotics as well as topical corticosteroids are some treatments that have been used. (1) In this case series, metronidazole was the topical antibiotic used. One patient improved on a topical regimen only, consisting of topical metronidazole and a selenium sulfide and sulfa combination wash. The other 2 patients required oral antibiotic treatment with either doxycycline or minocycline. All patients had considered discontinuing gefitinib secondary to the eruption's effect on their appearance. None had resolution of the eruption with the above treatment regimens; however, all experienced significant improvement that enabled them to continue on gefitinib. One patient subsequently had stabilization of his lung cancer, while another experienced a dramatic improvement. This reinforces the importance of a dermatologist's role in treating this eruption. With proper treatment some degree of improvement appears to be achievable which may make a patient more tolerant to continuing the EGFR inhibitor. This could result in a better outcome for the patient in regard to his or her cancer. As patients continue to receive gefitinib and other EGFR inhibitors, it is likely that this eruption will be more common. Randomized, controlled trials are needed to identify standardized, effective treatment protocols.