Skin Metastases

Clinical observations have suggested that the organ environment can influence the response of tumors to therapy. For example, in women with breast cancer, lymph node and skin metastases are more sensitive to chemotherapeutic intervention than metastases in either the lung or the bone (34). Similarly, orthotopic implantation of human tumor cells from surgical specimens into nude mice has shown that colon carcinomas injected into the wall of the colon, results in more clinically relevant outcomes then subcutaneously injected colon carcinomas. Orthotopic implanta-... 

Smorenburg CH, Seynaeve C,Bontenbal M, Planting AS, Sindermann H, Verweij J. 2000. Phase II study of miltefosine 6% solution as topical treatment of skin metastases in breast cancer patients. Anticancer Drugs 11 825-28... 

Terwogt JM, Mandjes IA, Sindermann H, Beijnen JH, ten Bokkel Huinink WW. 1999. Phase II trial of topically applied miltefosine solution in patients with skin-metastasized breast cancer. Br. J. Cancer 79 1158-61... 

Gehl, J. and Geertsen, P. (2000) Efficient palliation of hemorrhaging malignant melanoma skin metastases by electrochemoflierapy. Melanoma Research, 10, 585-589. 

A HPMA copolymer-paclitaxel conjugate was tested in phase I clinical studies showing again reduced side toxicity but also only partial remission of skin metastases in breast cancer patient. Also a HPMA copolymer conjugate with campthotecin was... 

Antineoplastic agents that cannot be grouped under subheadings 1-9 include miltefosine which is an alkylphosphocholine that is used to treat skin metastasis of breast cancer, and crispantase which breaks down asparagine to aspartic acid and ammonia. It is active against tumor cells that lack the enzyme asparaginase, such as acute lymphoblastic leukemia cells. Side effects include irritation of the skin in the case of miltefosine and anaphylactic reactions in the case of crispantase. Another recent development is the proteasome inhibitor bortezomib which is used to treat multiple myeloma. 

IV Mla Skin, subcutaneous tissue, or distant lymph nodes with normal lactate dehydrogenase Mlb Lung with normal lactate dehydrogenase Mlc To all other visceral sites (liver) or distant metastasis at any site with elevated serum LDH 7-19% 3-16%... 

The primary goals of therapy for skin cancer are to completely eradicate the tumor and minimize the risk of tumor recurrence and metastasis. Secondary goals of therapy include preserving normal tissue, maintaining function, and providing optimal cosmetic outcomes.5... 

Radiation is not standard therapy for the treatment of skin cancer however, there are circumstances in which radiation may be preferred. It is used as adjunctive therapy after surgical resection for patients with head and neck MM with metastasis to regional lymph nodes.40 Radiation is also indicated for patients with unresectable metastases or brain metastases or for palliation of symptoms from metastases.40 Older patients or patients who are poor candidates for surgery may be offered radiation as an option.40 Radiation offers good cosmetic results,... 

Metastasis is a process by which malignant cells leave their primary site and spread to distant locations throughout the body. It is the formation of metastasis that makes cancer such a lethal disease. The presence of metastasis is therefore the main cause of morbidity and mortality in patients with cancer. While primary tumors are potentially resectable, most metastases are resistant to all current forms of cancer treatment. Approximately 30% of patients with newly diagnosed solid cancers (excluding nonmelanoma skin cancers) have clinically detectable metastases, while another 30% may have occult micrometastases (L2). Clearly, to reduce mortality from cancer, we have to be able to prevent or treat metastasis. 

In humans, also, preferential sites exist for the formation of metastasis from various primary tumors [reviewed in Zetter (Zl)]. Thus, bone is a preferred site for metastasis from primary malignancies in breast, prostate, and kidney, while liver is a frequent metastatic site for tumors originating in the colon. Different types of leukemias vary widely in their ability to spread to liver, lymph, bone, and spleen. Some organs, however, are rarely colonized by metastatic growth. These resistant sites include skeletal muscle, heart, and skin. 

Epidermal growth factor receptor (HERl) PGFR Activation Increased cell proliferation, angiogenesis, metastasis and decreased apoptosis. Inhibition Skin rash, cancer metastasis. 

Toxicities are numerous and include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, hyperkalemia, altered mental status, seizures, and hirsutism. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) have been observed in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because the drug induces TGF-B, which promotes tumor invasion and metastasis. 

There is now sufficient epidemiological evidence to classify arsenic as a human carcinogen and a cause of skin cancer. In people chronically exposed to toxic doses of arsenic, such cancers may be preceded by discolored skin (hyperpigmentation) and development of homy skin surfaces (hyperkeratosis). These areas may progress to locally invasive basal cell carcinomas or to squamous cell carcinomas capable of metastasis. Unlike skin cancers that develop on skin exposed to ultraviolet solar radiation, arsenic-induced skin cancer frequently develops in areas not commonly exposed to sunlight, such as the palms of hands or soles of feet. 

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