Immunological Strategies to Fight Skin Cancer

B. Berman, MD, PhD; O. A. Perez, MD; D. Zell, MD

Disclosures

Skin Therapy Letter. 2006;11(5):1-7. 

In This Article

Interferon

In the United States, adjuvant high-dose interferon (IFN) therapy has become the standard of care for melanomas with a high risk of recurrence, and the FDA has approved the use of IFN-α-2b for the treatment of patients with melanomas thicker than 4mm and patients with lymph node metastasis. An early randomized prospective trial by Creagan, et al. did not find a significant difference between IFN-α-2b treated melanoma Stage I and II subjects vs. untreated controls. Although the experimental group had a longer disease-free survival (median, 17 months for the IFN-α-2b group vs. 10 months for the control group), the difference was not significant (p = 0.09).[1] However, when Rusciani, et al. evaluated Stage II melanoma IFN-α-2b treated subjects vs. Stage II untreated controls, they found a metastasis rate of 19.6% (10 of 51 treated subjects) vs. 60% (18 of 30 untreated controls) at 3 years follow-up (p < 0.0001), and a metastasis rate of 25% (4 of 16 treated subjects) vs. 63% (12 of 19 untreated controls) at 5 years follow-up (p < 0.005). The Stage I melanoma IFN-α-2b treated subjects did not have a significantly different disease progression than the untreated Stage I controls at 3 and 5 years follow-up.[2]

IFN-α-2b therapy appears to be more effective in patients with lesions that have a poor prognosis. A recent study examined the combination of IFN-α-2b and surgery in high-risk melanoma patients. In this retrospective study of 150 patients, adjuvant high-dose IFN was an effective treatment option for patients with high-risk melanoma (Stage IIC, III) after definitive surgery. The 2-year and 5-year relapse-free survival rates were estimated at 48% and 36%, respectively.[3] Table 1 .

The antiproliferative property of IFNs has also been employed in the treatment of patients with low-risk nodular basal cell carcinoma (nBCC) or superficial basal cell carcinoma (sBCC). Basal cell carcinoma (BCC) cells have been shown to express the CD95 ligand (FasL) and CD95 receptor (FasR), whereas the surrounding CD4+ T cells predominantly express FasR. Thus, in IFN treated patients, BCC may regress by FasR–FasL mediated apoptosis.[4] Intralesional IFN-α-2b at a concentration of 1.5 million international units (IU) used over a 3 to 4-week period has been shown to have an overall success rate of up to 100%.[5,6] However, when used for aggressive forms of BCC, this protocol has resulted in a cure rate of only 27% of treated patients.[7] Therefore, IFN treatment of BCC remains an alternative only for patients with low-risk nodular or superficial BCC.

Intralesional recombinant IFN-α-2b has been shown to be effective in the treatment of squamous cell carcinoma (SCC) and actinic keratosis (AK). When IFN-α-2b was administered at a dose of 1.5 million IU three times/week for 3 weeks to SCC lesions, 33 of 34 (97.1%) lesions showed an absence of SCC histologically.[8] However, when compared to other treatments for AK, the use of IFN is limited by the pain of injections and the multiple follow-up visits necessary.

IFN-α is one of the most effective single-therapy agents for the treatment of CTCL.[9] Low-grade, nonHodgkin, T-cell lymphomas are always associated with cutaneous involvement and include mycosis fungoides (MF) and the Sézary syndrome (SS).[10] A literature review by Bunn, et al. of 207 MF and SS cases treated with IFN-α-2a revealed an overall response rate of 55%, with 17% of cases being complete responders to IFN-α-2a therapy. These authors concluded that recombinant IFN-α-2a monotherapy has greater benefit in patients with early-stage disease, with 3 million IU of IFN-α-2a given subcutaneously three times/week being the optimal treatment regimen. In this study, no therapeutic differences were observed between IFN-α-2a and -2b.[11] A study by Vonderheid, et al. has revealed that intralesional injections of MF plaques with IFN-α-2b at a dose of 1 million IU given three times/week for 4 weeks produces substantial localized clinical and histological improvement with 10 of 12 plaques demonstrating complete regression localized to the IFN-α-2b injected sites.[12]

The use of IFN-α-2a and -2b in the treatment of KS in patients with acquired immune deficiency syndrome due to the human immunodeficiency virus has been approved by the US FDA. The recommended dosages for IFN-α-2a and -2b are 36 and 30 million IU subcutaneously three times/week, respectively. The average response rate of KS to high-dose IFN-α therapy has been approximately 30%. In many cases, tumor recurrence has been observed within 6 months after discontinuation of treatment, and response to subsequent treatments has not been reliable. This has led to indefinite treatment regimens until side-effects become intolerable.[13]

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