Neoadjuvant Approaches In Melanoma

摘要

Patients with clinically palpable regional lymph node metastases (AJCC stage IIIB-C) carry a risk of relapse and death that approaches 70% at 5 years. Surgical excision with complete regional lymph node dissection is the cornerstone of management, followed by adjuvant therapy with high-dose interferon-alpha2b (HDI). Neoadjuvant therapy has been demonstrated to improve outcome in the management of patients of multiple different solid tumors. In patients with melanoma, the quality of the host immune response differs between those with earlier and those with more advanced disease settings. Host immune tolerance is now understood to impede the results of therapy for advanced disease, but may be less an issue for patients with microscopic high-risk operable disease, where the host may be more susceptible to immunologic interventions. Phase II studies have shown that neoadjuvant biochemotherapy has limited activity in melanoma patients with local-regional metastases, where chemotherapy may potentially antagonize or alter the effects of immunotherapeutic agents. Studies of neoadjuvant HDI therapy for high-risk melanoma patients with bulky regional stage IIIB-C lymphadenopathy are ongoing and preliminary results have shown unexpectedly high clinical and pathologic response rates, without increased morbidity. Through the design of neoadjuvant trials in which it is possible too btain biopsy samples before and after therapy, a greater understanding of the dynamic interaction between tumors and the immune system is possible. This should lead to the identification of new targets for the treatment of melanoma and aid the development of new immunotherapies that may have greater specificity and less toxicity. This will simplify the evaluation of promising new combinations of agents with HDI to build on the clinical, immunologic, and molecular effect of this therapy for patients with melanoma.