Topical Combination of Fluorouracil and Calcipotriene as a Palliative Therapy for Refractory Extramammary Paget Disease

Molina, Gabriel E.; Khalifian, Saami; Mull, Jamie L.; Chen, Lu; Rosman, Ilana S.; Faulkner-Jones, Beverly E.; Ngo, Kenneth; Demehri, Shadmehr; Cornelius, Lynn A.; Wu, Peggy

doi:10.1001/jamadermatol.2018.4793

Cited by 26 publications

(24 citation statements)

References 8 publications

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“…Radiation therapy is considered a treatment strategy in patients who were poor surgical candidates [31]. Other non-surgical treatments such as 5-fluorouracil or topical imiquimod have been used either in non-invasive or recurrent PPD [18,32,33]. photodynamic therapy with topically applied 5aminolevulinic acid has been reported to treat non-invasive PPD and achieved complete cure without recurrence [34].…”

Section: Discussionmentioning

confidence: 99%

Perianal Paget’s disease: a clinicopathological and immunohistochemical study of 13 cases

et al. 2020

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Background: Perianal Paget's disease (PPD) is rare and mostly described in clinical literature as case reports or small series. Methods: We investigated the clinicopathologic and immunohistochemical features of PPD in a total of 13 cases retrieved from multiple academic institutions. Results: The median age at diagnosis was 75 (range 50-86) years. Males were predominant with a male to female ratio of 2.25:1. Four (30.8%) cases were classified as primary PPD due to lack of synchronous or metachronous underlying malignancies, while nine (69.2%) were classified as secondary PPD with concurrent invasive adenocarcinoma (n = 8) or tubular adenoma with high-grade dysplasia (n = 1). Immunohistochemically, there is no differential expression of CK7 or CK20 in Paget's cells between primary and secondary PPD; however, GCDFP-15 was only positive in primary PPD (3/3 vs. 0/6, P = 0.012), while CDX2 was only positive in secondary PPD (0/3 vs. 7/7, P = 0.008), suggesting different cell origin. All patients received local surgical resection with or without adjuvant therapy. After a median followup of 47 months, one patient with secondary PPD (7.7%) died of disease progression from underlying adenocarcinoma. Conclusions: PPD occurs in elderly patients with male predominance and is frequently associated with underlying malignancies. Differential expression of CDX2 and GCDFP-15 may help distinguishing primary vs. secondary PPD, which is important for management as the presence of an underlying malignancy impacts clinical course and prognosis. Surgical excision remains the major treatment strategy for PPD. Long-term follow-up is required to monitor the disease recurrence and metastasis.

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Section: Discussionmentioning

confidence: 99%

Perianal Paget’s disease: a clinicopathological and immunohistochemical study of 13 cases

et al. 2020

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“…The 43 eligible studies were all observational and included a total of 341 patients: 7 prospective cohort studies (grade of evidence A), 89 patients; 19 retrospective cohort studies (grade of evidence B), 179 patients, and 17 small cases series (grade of evidence C), 72 patients [16-58]. All were published in peer-reviewed journals except 1 (imiquimod study) which was extracted from a conference abstract [48].…”

Section: Resultsmentioning

confidence: 99%

“…One small case series investigated the effectiveness of treatment with 5% 5-FU cream and 0.005% calcipotriene in 3 patients with EMPD that was refractory to treatment with imiquimod, surgery, and/or irradiation. Cream was applied twice daily for 1–8 days per month [58]. None of the patients achieved CR, but all showed clinical improvement, with well-tolerated treatment-site-restricted side effects.…”

Section: Resultsmentioning

confidence: 99%

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Nonsurgical Treatments for Extramammary Paget Disease: A Systematic Review and Meta-Analysis

et al. 2020

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Introduction: Surgery is commonly regarded as the mainstay of treatment of extramammary Paget disease (EMPD); however, nonsurgical approaches have gained popularity in recent years. Objectives: To review the published evidence for the efficacy and safety of nonsurgical modes of therapy for EMPD. Methods: A systematic review and meta-analysis of nonsurgical EMPD treatments was performed. The primary outcome was complete response (CR); secondary outcomes were clinical regression by ≥50%, adverse events, and recurrence rate. Results: The systematic review included 43 observational studies (341 patients; 7 prospective cohort studies, 19 retrospective cohort studies, and 17 cases series) evaluating 5 treatment modalities. Imiquimod (13 studies, 110 patients) administered at variable doses ranging from daily to twice weekly for 2-56 weeks demonstrated CR of 54% (95% CI, 40-67%; I 2 = 37%) and had a satisfactory safety profile. In 14 heterogeneous studies (122 patients) evaluating photodynamic therapy (PDT), only 36% (95% CI, 22-53%; I 2 = 52%) of patients achieved CR. Radiotherapy (12 studies, 67 patients) showed CR of 97%, but was associated with local and systemic side effects. Ablative lasers and topical fluorouracil and calcipotriene lacked adequate evidence of efficacy. Conclusions: Imiquimod and radiotherapy are the most appropriate nonsurgical modalities for EMPD treatment given their good efficacy and safety profile. PDT has limited efficacy but may be appropriate in selected clinical settings.

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“…In clinical practice, sonophoresis is commonly used in rehabilitation medicine and dermatology because of its role in increasing the permeability of drugs (such as arthritis, Paget disease, keloid and hypertrophic scars). 27,28 With the development of ultrasonic technology, sonophoresis also has been used in anesthesia and gene therapy. 29,30 A recent study reported the use of HFS for the delivery of a monoclonal antibody to different in vitro cancer cell lines for treatment against human papilloma virus (HPV) oncoprotein E6.…”

Section: Discussionmentioning

confidence: 99%

<p>Sonophoresis Enhanced Transdermal Delivery of Cisplatin in the Xenografted Tumor Model of Cervical Cancer</p>

Ma¹,

Liu²,

Li³

et al. 2020

OTT

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These authors contributed equally to this work Background: Transdermal drug delivery system has been researched for a long time because of its advantage in decreasing side effects such as nausea, vomiting, and gastrointestinal disturbance. Sonophoresis has been shown to be very effective in promoting the transdermal delivery of drugs. This study is on purpose to research the feasibility of sonophoresis promoting cisplatin in the treatment of cervical cancer and the optimum drug delivery mode. Methods: Thirty-two female nude-mice model of cervical cancer were randomly divided into 4 groups (n=8 in each group): control group without any intervention, low, medium and high concentration groups were treated with the corresponding cisplatin concentrations of 0.2mg/mL, 0.4mg/mL and 0.8mg/mL, respectively, with concurrent sonophoresis applied on the skin of local tumor, 1 mL at a time, once a day for a total of 5 days. Therapeutic pulsed ultrasound (TPU) was 1.0 MHz, 2.0 W/cm 2 and 60-min duration. Weight of mice and tumor diameters were measured every day during the intervention. The concentration of cisplatin in tumors was detected by HPLC. Meanwhile, tumor, skin, liver and kidney gross structures and ultrastructure were observed in order to evaluate the effectiveness and safety of experimental conditions. In addition, apoptosis and proliferation-related factors (MPO, Caspase-3, PCNA) were detected by immunohistochemistry, immunofluorescence and TUNEL assay. Results: The weight of nude mice in each group showed an increasing trend, except for a decrease of weight in the 0.8 mg/mL group. No obvious tumor inhibition effect was observed. Cisplatin was detected in the 0.4 mg/mL group and 0.8 mg/mL group, with relative concentrations of 0.081±0.033 mg/mL and 0.111±0.021 mg/mL, respectively. Both skin and kidney inflammation were observed in the 0.8 mg/mL group. The expression of MPO, caspase-3 and TUNEL was concentration dependent, with the highest expression in the 0.8 mg/mL group, followed by the 0.4 mg/mL group, with no significant differences between the control and the 0.2 mg/mL group. PCNA was highly expressed in both the control and 0.2 mg/mL groups but decreased in the 0.4 mg/mL and 0.8 mg/mL groups. Conclusion: Sonophoresis enhanced transdermal delivery of cisplatin in a xenograft tumor model of cervical cancer. Considering the occurrence of skin inflammation and renal injury caused by cisplatin, the recommended concentration to be administered is 0.4mg/mL.

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Topical Combination of Fluorouracil and Calcipotriene as a Palliative Therapy for Refractory Extramammary Paget Disease

Cited by 26 publications

References 8 publications

Perianal Paget’s disease: a clinicopathological and immunohistochemical study of 13 cases

Perianal Paget’s disease: a clinicopathological and immunohistochemical study of 13 cases

Nonsurgical Treatments for Extramammary Paget Disease: A Systematic Review and Meta-Analysis

<p>Sonophoresis Enhanced Transdermal Delivery of Cisplatin in the Xenografted Tumor Model of Cervical Cancer</p>

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