New Topical Immunotherapy for Metastatic Melanoma

Dr Webber’s team at the Princess Alexandra Hospital Department of Dermatology offer a novel new therapy for cutaneous metastatic melanoma.

Patients with in-transit cutaneous melanoma metastases have an average 5-year survival of 44%, whilst only 10% of those patients with visceral metastases are alive at 5 years. Current treatments for metastatic disease offer limited efficacy. Response rates in the order of 10-15% are observed with either systemic chemotherapy with agents such as dacarbazine (DTIC) or systemic interferon. Regional chemotherapy such as isolated limb infusion (ILI) confers good local control in many patients with lesions on the (non-proximal) limbs, with reported complete responses in one third of patients and partial responses in another 45%. These responses last on average for only a year however, and ILI is unable to treat or prevent distant disease. Regional chemotherapy is also unsuitable for lesions on the trunk, head and neck or proximal limbs.

Spontaneous regression of metastatic melanoma occasionally occurs, implying a role for immune mechanisms in the control of this disease. Diphencyprone (diphenylcyclopropenone; DPCP) is a potent contact sensitizer. DPCP induces a contact hypersensitivity (CHS) response that presumably incites lymphocyte-mediated tumour destruction via increased TNF, IFN-gamma and IL-6. It is thought that manipulation of IL-17 and upregulation of CD70 co-stimulatory pathways potentially has anti-tumour effects via T-cells and natural killer cells.

Diphencyprone (DPCP) has been used for a number of years both in Australia and overseas for the treatment of autoimmune hair loss (alopecia areata). It is now an accepted treatment option for patients with extensive or refractory alopecia areata. DPCP is also used to treat viral cutaneous warts. Hence this inexpensive, relatively non-invasive topical treatment is already in common use for non-malignant conditions, with established tolerability and safety.

Since 2011, Dr Webber and his team at the Princess Alexandra Hospital Department of Dermatology in Brisbane have been using DPCP for the treatment of cutaneous localised metastatic melanoma on patients. Particularly suited for patients with extensive disease localised to the skin, DPCP immunotherapy offers melanoma patients another option for treatment, particularly where further surgery or more invasive treatments may not be well suited or tolerated by the patient.

The process of DPCP immunotherapy initially involves sensitisation of patients to diphencyprone. This is performed in the hospital outpatient setting. The second stage of treatment involves the application of diluted concentrations of diphencyprone directly to the site of the cutaneous melanoma. This 2nd stage of treatment elicits a contact dermatitis reaction on the skin. This reaction is maintained with regular weekly applications of DPCP to the site. The treatment reaction is regularly reviewed and modified by Dr Webber’s team to ensure an appropriate response is maintained.

As highlighted by Dr Webber, “Early results from our work with DPCP have identified a complete response in approximately 12% of patients with clinical and histopathological clearance of the melanoma. About two thirds of patients have had a partial response with slowing of the progression of melanoma or continued disease regression. Unfortunately about one third of patients fail to demonstrate a response to the DPCP.”

Before treatment with DPCP

At Week 28 of DPCP treatment


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