5-(3,3-Dimethyle-1-Triazeno) Imidazole-4-Carboxamide and Interleukin-2 Adjuvant Therapy in Resected High-Risk Primary and Regionally Metastatic Melanoma.
IL-2 in combination with chemotherapeutic agents such as flavone acetic acid, dacarbazine, and cyclophosphamide have also been studied in patients with metastatic melanoma.
IL2 is a type I cytokine that is associated, when given at high doses intravenously, with durable regressionin a subset of patients with metastatic melanoma and renal cell carcinoma, yet high toxicity limits its use.
A consecutive series of 409 patients with either metastatic melanoma or renal cancer who were treated with high-dose bolus IL-2 in the Surgery Branch, National Cancer Institute, between September 1985 and November 1996 have been analyzed with a median potential follow-up of 7.1 years.
Adoptive cell therapy (ACT) with ex vivo expanded tumour-infiltrating lymphocytes (TILs) in combination with IL-2 is an effective treatment for metastatic melanoma.
All MM cases (excluding ocular MM, n = 837) diagnosed in three non-consecutive years marked by major changes in the first-line treatments (2012: interleukin-2 and BRAF inhibitors; 2014: anti-CTLA-4: Cytotoxic T-Lymphocyte Antigen 4 and 2016: anti-PD-1: programmed cell death protein 1 and MEK inhibitors) were retrieved.
Based on its ability to stimulate cytotoxic T cells, interleukin-2 (IL-2) has been used to treat patients with metastatic melanoma and metastatic kidney cancer.
Clinical trials using IL-2 for metastatic melanoma therapy that reported: dosage, combinations, study details, definitions and clinical CR, PR, and overall response (OR) rates were included.
Combined treatment with ipilimumab and intratumoral interleukin-2 in pretreated patients with stage IV melanoma-safety and efficacy in a phase II study.
Considering tumor-induced suppression of lymphocytes the aim of this study was to investigate in vitro effects of IFN-α, IL-2, IL-12 and IL-18 as immunomodulating agents on the functional and receptor characteristics of peripheral blood lymphocytes (PBL) in metastatic melanoma (MM) patients compared to healthy controls (HC).
Despite increasing use of "targeted therapy," interleukin-2 (IL-2) is unique, because this cytokine can induce long-term remissions in 5% to 7% of patients with metastatic melanoma and renal cancer.
Furthermore, we have found an association between the presence of N-ras mutations and clinical response to immunotherapy with interleukin-2 plus interferon in a group of stage IV melanoma patients.
High-dose interleukin-2 and interferon as first-line immunotherapy for metastatic melanoma: long-term follow-up in a large unselected Danish patient cohort.
In 1998, high-dose interleukin-2 (IL-2) was the first immunotherapy approved for the treatment of metastatic melanoma based on durable objective responses documented in a subset of patients but widespread utilization was limited by significant toxicity.
Of note, we had previously reported a similar phenomenon in patients with metastatic melanoma who failed high dose interleukin-2 and were then placed on a finite course of temozolomide with rapid complete responses that have remained durable for many years after discontinuation of temozolomide.
Part II of this continuing medical education article will discuss the treatment options for stage IV melanoma, including novel therapies, such as ipilimumab and vemurafenib; established therapies, including high-dose interleukin-2, conventional chemotherapy, and biochemotherapy; and additional therapies currently under investigation in the form of clinical trials.