Adjuvant Therapy: Melanoma

Abstract

With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway.

Time-Dependent Stabilization of Hypoxia Inducible Factor-1α by Different Intracellular Sources of Reactive Oxygen Species

“…The exact mechanisms exploited by aggressive melanoma to achieve this high intrinsic drug resistance is currently unknown and is at present a real challenge for molecular oncologists. Indeed, up to now immunotherapy using interleukin-2 and interferon-γ is the most used pharmacological approach for this kind of neoplasia [26] . Herein we report that etoposide resistance in human aggressive melanoma Hs29-4T cells is tightly correlated to a two waved redox-based VEGF autocrine loop, exploiting hypoxic environment.…”

CRISPR/Cas9-Mediated Treatment Ameliorates the Phenotype of the Epidermolytic Palmoplantar Keratoderma-like Mouse

“…After the genomic changes occur following the transduction of the CRISPR/Cas9 system, using cytokines as adjuvant therapy to accelerate regeneration could be a feasible means of enhancing the therapeutic efficacy. 43 , 44 Unlike the general therapeutic strategies for genetic diseases targeting either the genetic cause underlying a specific disorder or disease-specific pathophysiological pathways, the current standard care for EPPK and other keratin disorders still only has retinoids for treating the hyperkeratosis, focusing on symptomatic treatment. Although the CRISPR/Cas9 system had a significant effect on adult Krt9 /KI mice after local injection, we predict that this therapy could be more effective with adjuvant treatment.…”

Advances in Adjuvant Therapy for the Treatment of High-risk Melanoma

“…Radiotherapy may be valuable in the adjuvant setting in patients with bulky disease of involvement of nodes, particularly for those with the potential for a highly symptomatic nodal relapse. 6 The use of radiotherapy as adjuvant has been investigated in a phase III trial, but although it improved regional control, it did not improve OS. 53 Further work from this group presented at this last year's ASCO confirmed the RFS advantage, but lack of OS and trend toward decreased quality of life suggest careful selection of patients where decrease in relapse outweighs the potential morbidity in terms of lymphedema risk.…”

“…Numerous candidate molecules have been studied, including methylthioadenosine phosphorylase expression, YKL-40, S100B, melanoma-inhibiting activity, and tumor-associated antigen 90 immune complex. 6 However, there is a lack of prospective data validating the use of these biomarkers.…”

“…4 The probability of recurrence is defined as low, intermediate, or high risk depending on the thickness of the primary tumor, the presence of ulceration or mitoses in the primary tumor, and the presence of nodal or in-transit or satellite metastases around the primary lesion. 5,6 Adjuvant therapy is offered after surgical treatment has removed all detectable disease and is given with the intent of reducing relapse risk due to occult disease. Adjuvant therapy should be considered for patients whose risk for recurrence exceeds 30 %, i.e.…”