- L A Walkington, consultant medical oncologist1,
- P Lorigan, senior lecturer in medical oncology2,
- S J Danson, senior lecturer and consultant medical oncologist1
- 1Weston Park Hospital, Sheffield S10 2SJ, UK
- 2Christie NHS Foundation Trust Hospital, Manchester, UK
Patients diagnosed with thin cutaneous melanoma usually have a good prognosis after surgical resection, but prognosis is poor for those who present with, or develop, metastatic malignant melanoma (stage IV disease). Average survival is less than 12 months, and this has remained unchanged for more than 20 years.1 The mainstay of treatment in advanced melanoma has been dacarbazine chemotherapy, which has a poor response rate of 8-10%.1 However, the past three years have seen important advances in systemic treatment options for patients with this disease. Two treatment strategies, based on immunotherapy and genomics, now offer real hope of improved quality of life and prolonged survival, albeit with a serious risk of side effects and high drug costs.
It is now clear that the immune system has an important influence on the outcome of several cancers not previously thought to be immunogenic.2 Melanoma is an immunogenic tumour in that it expresses melanoma specific antigens, and a clinical response to immunotherapy has been shown. Better understanding of the complex molecular interactions needed to generate an immune response has led to the development of effective new immunotherapy agents.
Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) is a key negative regulatory molecule. It is expressed on the surface of T cells shortly after activation by antigen presenting cells and inhibits the immune response. Ipilimumab is a fully humanised monoclonal antibody that competitively binds CTLA-4, resulting in increased T cell activation and proliferation.
A phase III trial randomised patients with metastatic …