Abstract
In 2012, it was estimated that 9180 people in the United States would die from melanoma and that more than 76,000 new cases would be diagnosed. Surgical resection is effective for early-stage melanoma, but outcomes are poor for patients with advanced disease. Expression of tumor-associated antigens by melanoma cells makes the disease a promising candidate for immunotherapy. The hematopoietic cytokine granulocyte–macrophage colony-stimulating factor (GM-CSF) has a variety of effects on the immune system including activation of T cells and maturation of dendritic cells, as well as an ability to promote humoral and cell-mediated responses. Given its immunobiology, there has been interest in strategies incorporating GM-CSF in the treatment of melanoma. Preclinical studies with GM-CSF have suggested that it has antitumor activity against melanoma and can enhance the activity of anti-melanoma vaccines. Numerous clinical studies have evaluated recombinant GM-CSF as a monotherapy, as adjuvant with or without cancer vaccines, or in combination with chemotherapy. Although there have been suggestions of clinical benefit in some studies, results have been inconsistent. More recently, novel approaches incorporating GM-CSF in the treatment of melanoma have been evaluated. These have included oncolytic immunotherapy with the GM-CSF–expressing engineered herpes simplex virus talimogene laherparepvec and administration of GM-CSF in combination with ipilimumab, both of which have improved patient outcomes in phase 3 studies. This review describes the diverse body of preclinical and clinical evidence regarding use of GM-CSF in the treatment of melanoma.
Highlights
In 2012, it was estimated that 9180 people in the United States would die from melanoma and more than 76,000 new cases would be diagnosed [1]
granulocyte–macrophage colony-stimulating factor (GM-CSF) administered with a heat shock protein vaccine has been implicated in the induction of myeloid-derived suppressor cells (MDSC) in melanoma patients [83]
There was initial enthusiasm for recombinant GM-CSF based on uncontrolled clinical trials in stage III/IV melanoma, therapeutic benefit has not been confirmed in larger, prospective, randomized trials
Summary
In 2012, it was estimated that 9180 people in the United States would die from melanoma and more than 76,000 new cases would be diagnosed [1]. In a phase 2 study, there were statistically significant improvements in survival among patients with stage III/IV disease (P = 0.04 and P < 0.001, respectively) receiving GM-CSF (125 μg/m2 daily for 14 consecutive days in 28-day cycles up to 1 year) compared with historical controls [37]. AGC = absolute granulocyte count; ANC = absolute neutrophil count; BCNU = carmustine; CDDP = cisplatin; CR = complete response; CTX = cyclophosphamide; DOX = docetaxel; DTIC = dacarbazine; FLU = fludarabine; GM-CSF = granulocyte-macrophage colony-stimulating factor; IFN-α = interferon-α; IL-2 = interleukin-2; MESNA = sodium 2-mercaptoethanesulfonate; MR = mixed response; OS = overall survival; OX = oxaliplatin; PFS = progression-free survival; PR = partial response; SD = stable disease; TAM = tamoxifen; TMZ = temozolomide; VBL = vinblastine; VIN = vinorelbine.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
