Abstract 2709: Propopsed new approach of adjuvant therapy in human cutaneous melanoma

Abstract

Abstract Adjuvant therapy is administered in the form of systemic treatment after complete resection of the melanoma in patients with high risk of recurrence, to prolong the disease free survival (DFS) and overall survival (OS). This has been met with limited success and new approaches are needed. Cutaneous melanoma is characterized by an initial skin lesion, and the development of satellitosis and intransit metastases that are amenable to clinical inspection, palpation and intralesional therapy. Methods: Published data from 3 research areas were reviewed: 1. Management of satellitosis and intransit metastases. 2. Effect of administering Granulocyte-macrophage colony stimulating factor (GM-CSF) at the primary site on sentinel lymph node (SLN). 3. Factors identified in metastatic melanoma and in patients with metastases that reflect on survival. Results: 1. Repeated intralesional injections of satellitosis and intransit metastases with GM-CSF or interleukin-2 (IL-2) gave high clinical response rates of durable durations. 2. GM-CSF administration in the skin at the primary site increased the number and activation of dendritic cells (DC) and CD8+ cells at sub-cortical zone of SLN. 3. The presence of tumor specific T cells in metastatic lesions have significant survival benefit, while the presence of these cells in the peripheral blood does not. Further, induction of high levels of tumor specific CD8+ T cells in the circulation does not prevent tumor progression. Hypothesis: To utilize the primary site and its draining lymph node(s) for immune manipulation prior to their excision. The administration of GM-CSF at the primary site, where tumor cells or their debris are present, can activate DC (s) which are efficient antigen presenting cells that can process tumor antigens and cross-talk to T cells. On the other hand, IL-2 activates NK, CD8+ cells and TIL. The presence of DC, CD8+, TIL and patient's own tumor and T cells can induce major immune response and may give rise to autologous-tumor-specific cytotoxic T cells in vivo. This should precede any systemic therapy that should be aimed at maximizing this response and hopefully improving survival. Proposal: Newly diagnosed patients with high risk melanoma who are candidates for SLN biopsy can be randomized to receive standard surgical treatment [SLN biopsy and wide excision of the primary site] vs preoperative administration of GM-CSF 500μg on day 1 and IL-2 11×106 IU/day on days 2 &3 at the primary site, 1-2 weeks prior to standard surgical treatment. Systemic therapy that consists of same low doses of GM-CSF and IL-2 should be considered in patients with lymph node metastases. The 2 groups of patients are to be compared for DFS and OS. The tissues should be evaluated for tumor necrosis and histiocytosis at the injection sites, as well as for CD3, CD4, CD8, CD25, and CD83 both at the primary site and lymph nodes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2709. doi:10.1158/1538-7445.AM2011-2709