taxane and Melanoma

Systemic agents are used in melanoma for adjuvant therapy and to treat metastatic disease. Currently, interferon-α is the only agent approved for adjuvant therapy. Six drugs are FDA approved for metastatic disease: dacarbazine, interleukin-2 (IL-2), vemurafenib, ipilimumab, dabrafenib, and trametinib. Vemurafenib and ipilimumab were approved in 2011, whereas dabrafenib and trametinib were approved in 2013.. This review will update the practicing dermatologist on the differences in efficacy, adverse events, and cost of systemic therapies available for the treatment of melanoma.. This article is a review of the current literature on systemic therapies for advanced melanoma. Key search words included "advanced melanoma," "systemic therapy," and "adjuvant therapy" with particular focus on the past 20 years.. Before 2011, dacarbazine and IL-2 were the only FDA approved therapies for metastatic melanoma, and IFN-α is the only approved agent for adjuvant therapy. The new agents vemurafenib, ipilimumab, dabrafenib, and trametinib are the first to have improved overall survival in Phase III studies in comparison with other systemic therapies.. Despite new developments, there remains a significant need for better therapies with improved long-term efficacy and decreased toxicity.

Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents; Bridged-Ring Compounds; Dacarbazine; Humans; Imidazoles; Indoles; Interferon-alpha; Interleukin-2; Ipilimumab; Melanoma; Oximes; Platinum Compounds; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; Skin Neoplasms; Sulfonamides; Taxoids; Temozolomide; Vemurafenib

The role of systemic chemotherapy in the treatment of patients with metastatic melanoma remains of questionable benefit. Despite encouraging phase II data from multiple institutions that suggested an improved overall response rate for patients treated with the Dartmouth regimen, recently completed phase III trials have failed to demonstrate a significant benefit in survival. Of concern is the fact that there have been relatively few new chemotherapeutic agents in the past several years that have demonstrated any activity in this disease. More recently there has been a shift away from combination chemotherapy to biochemotherapy. However, this approach has yet to be clearly defined as superior. The basis for optimism in the future in this field resides in the realm of molecular oncology. As mechanisms of resistance are identified, new molecules such as antisense oligonucleotides may provide the basis for increasing the sensitivity of melanoma to chemotherapeutic and/or immunotherapeutic treatments.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carmustine; Cisplatin; Clinical Trials as Topic; Dacarbazine; Humans; Melanoma; Nitrosourea Compounds; Paclitaxel; Tamoxifen; Taxoids; Temozolomide

The incidence of cutaneous melanoma has been rapidly increasing, with an estimate of 47,700 new cases diagnosed in 2000 in the United States. In the early phase of its natural history, melanoma is cured in most cases by surgery, but once the metastatic phase develops, it is almost always fatal. The treatment of metastatic melanoma remains unsatisfactory. Systemic therapy has not been successful up to now, with very low response rates to single-agent chemotherapy. Polychemotherapy has increased the response rate (RR), without a significant improvement in overall survival. Immunotherapy alone is able to induce only a few durable complete responses (CRs). New chemotherapeutic and biologic agents are now available and promising combined approaches targeting the tumor by several different mechanisms are desirable and will probably represent the future modality of treatment.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Cisplatin; Clinical Trials as Topic; Cytokines; Dacarbazine; Genetic Therapy; Humans; Immunotherapy; Interferon-alpha; Interleukin-2; Melanoma; Nitrosourea Compounds; Organophosphorus Compounds; Paclitaxel; Tamoxifen; Taxoids; Thalidomide

The apoptosis stimulator STA-4783 acts by inducing expression of heat shock protein (Hsp)70 on tumor cell surfaces and disrupting the cytoskeletal network. Currently in development by Synta Pharmaceuticals for the potential treatment of solid tumors, phase II clinical trials in non-small-cell lung cancer, melanoma and sarcoma have been initiated.

Topics: Animals; Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Gene Expression Regulation, Neoplastic; HSP70 Heat-Shock Proteins; Humans; Hydrazines; Lung Neoplasms; Melanoma; RNA, Messenger; Taxoids; Tubulin Modulators