Fluorouracil Plus Calcipotriene May Help Refractory Extramammary Paget Disease

By Marilynn Larkin

March 04, 2019

NEW YORK (Reuters Health) - In patients who fail other therapies for extramammary Paget disease (EMPD), palliative therapy with topical fluorouracil and calcipotriene may be an option, a small case series suggests.

"EMPD occurs most frequently in the groin and genital area, and treatment is associated with a significant amount of morbidity and high recurrence rates," Dr. Peggy Wu of the University of California, Davis in Sacramento told Reuters Health by email.

"Because EMPD disproportionally affects a part of the body that is functionally, psychologically, and socially significant, optimizing treatment to deliver the greatest benefit while minimizing side effects is paramount," said Dr. Wu, who was at Beth Israel Deaconess Medical Center in Boston during the study.

"Most patients are offered surgery as initial therapy, but even with the movement towards tissue-sparing Mohs surgery, the potentially disfiguring nature of surgery is challenging," she noted. "Although other modalities, such as radiation, chemotherapy, and photodynamic therapy have also been tried, the data on efficacy are limited at best. Thus, finding a topical therapy which is both well-tolerated and efficacious would be ideal."

"In this series of patients, we tried a more commonly used topical therapy in the literature, imiquimod, without improvement and/or with intolerable side effects," she said. "Inspired by the antineoplastic effects of calcipotriene, an immunomodulatory agent, and fluorouracil, an antimetabolite topical chemotherapy, in treating actinic keratoses, we felt it might be an option for these patients with recurrent or recalcitrant EMPD."

In their JAMA Dermatology report, online February 20, Dr. Wu and colleagues described three women (one in her 50s, two in their 70s) who presented with recurrent EMPD (vulvar, perianal, and perioral) after surgery and/or irradiation, and whose EMPD was refractory to treatment with imiquimod 5% cream.

The women began treatment with a 1:1 mixture of fluorouracil 5% cream and calcipotriene 0.005% cream. They applied the topical therapy to the affected areas with differing frequencies, ranging from one to two days per month to four consecutive days every two weeks.

The treatment was well tolerated and, in all three cases, led to clinical improvement in symptoms, including pruritus and discomfort, and in the appearance of the lesions (reduced thickness and peripheral extension of the lesions). Histopathological signs of decreased tumor burden occurred in two women.

"Our results were encouraging, particularly in that the side effects seemed to be more tolerable and the therapy was able to at least slow progression, if not improve the disease," Dr. Wu said.

"Additional studies would be needed on more patients to explore the ideal timing relative to other therapies and directions for use," she added. "For now, it would still be considered a palliative therapy, and recommended for patients under consideration for topical therapy, such as those who have already undergone surgery or radiotherapy and have residual disease or recurrent disease."

Dermatologist Dr. Saakshi Khattri, an assistant professor at Icahn School of Medicine at Mount Sinai in New York City, told Reuters Health in an email, "Based on the data presented, this combination is worth considering," which she will now do for refractory cases.

That said, she added, "Use of calcipotriene in intertriginous areas causes cutaneous irritation and EMPD can be/is seen in intertriginous areas (inguinal folds), so there is a possibility of non-compliance if side effects are intolerable."

Two coauthors are co-inventors on a patent for the use of fluorouracil and calcipotriene in the treatment of precancerous skin lesions.

SOURCE: http://bit.ly/2UfTq9E

JAMA Dermatol 2019.

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