* When I first started out trying to figure out what therapies I should try, Dee and I worked with Dr Kirkwood and developed a plan of attack (a flow diagram). We put together if and than statements to create a path forward. Coming from a research environment, this made the most practical sense.
So here is my path.
* Most of information was taken from an article written by Adil I. Daud, MDJeffrey S. Weber, MD, PhD entitled:
* “Novel Treatment Approaches For Patients With Metastatic Melanoma”
* Release Date: August 30, 2007
Introduction
According to the American Academy of Dermatology, an estimated 108,230 new cases of melanoma will be diagnosed in the United States in 2007, including 48,290 in situ and 59,940 invasive cases.[1] Invasive melanoma is the fifth most common cancer in men and women. About 8000 deaths from melanoma are expected in 2007 in the United States.[1]
Melanoma is a cancer of the melanocyte, a long-lived pigment-producing cell normally found at the dermo-epidermal junction within the skin. During the process of transformation of melanocytes to melanoma, histologic and clinical changes occur.[2] The initial stage of transformation can result in an atypical or dysplastic nevus. The next stage is the so-called epidermal radial growth phase (RGP) melanoma, which involves proliferation of the transformed melanocytes in the epidermis. This is followed by an invasive RGP melanoma wherein the tumor cells invade the dermis. In the next phase, the vertical growth phase, melanocytes proliferate in the dermis and are competent for metastatic invasion. Finally, the metastatic phase is characterized by invasion of lymph nodes and distant organs.
Based on a rigorous statistical analysis of a large sample of patients with melanoma, the American Joint Committee on Cancer proposed revised staging guidelines in 2002. These guidelines are useful for clinical management of patients and for analyzing clinical trial data discussed in this review.[3,4]
Stages I and II are melanomas that are localized to the skin, at varying depths of invasion:
stage III includes patients with regional recurrence and nodal spread of disease, and stage IV patients have distant metastatic spread of melanoma.
Currently, 3 drugs are approved for the treatment of metastatic melanoma:
dacarbazine (DTIC), hydroxyurea, and interleukin-2 (IL-2).
None has ever been tested in a randomized phase 3 trial against a control and been shown to prolong survival. DTIC and hydroxyurea were approved by the US Food and Drug Administration (FDA) more than 20 years ago and would be unlikely to meet current standards for FDA approval. The only approved immunotherapy for melanoma, IL-2,[5] is a toxic agent employed in a complex regimen used by a restricted number of centers in the United States today. Practice guidelines promulgated by organizations such as the National Comprehensive Cancer Network (NCCN) indicate that entry into a clinical trial is an acceptable standard of care for patients with newly diagnosed stage IV melanoma.[6] In fact, the NCCN decision tree for patients with stage IV melanoma with multiple metastases indicates that a clinical trial is the first choice, followed by DTIC or IL-2; lower priority choices include DTIC with other agents in combination. For patients with a small volume of disease, a watch-and-wait plan is considered acceptable, an admission that the armamentarium of drugs for metastatic melanoma is deficient.
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