Evolution of systemic treatment approaches

BRAF targets in melanoma. Biological mechanisms, resistance, and drug discovery. Cancer drug discovery and development. Volume 82. Ed. Ryan J. Sullivan. Springer (2015)


The prognosis for patients with Stage IV melanoma has historically been poor with median survival less than a year and a 5-year overall survival rate of less than 10%. Two US Food and Drug Administration (FDA) approved drugs had been used for the treatment of patients with Stage IV melanoma in the US prior to 2011, namely, DTIC and recombinant human interleukin-2 (IL-2). Recent advances in melanoma therapy have been dramatic with the approval of ipilimumab and vemurafenib in the US in 2011 followed by approval of dabrafenib and trametinib in 2013. Greater understanding of melanoma biology coupled with the successful development of novel treatments such as anti-PD-1 antibody and new combination regimens will further improve patient outcomes in the future.

Cytotoxic chemotherapy

The objective response rate of DTIC is approximately 10–20% with most responses ranging from 3 to 6 months, although long-term remissions can occur in a small number of patients who achieve a complete response. Despite its FDA approval DTIC has never been shown to improve median progression free survival or overall survival compared to a control arm in any prospective randomized study. Although combinations of cytotoxic agents, including those containing DTIC or regimens adding either IFN or tamoxifen to DTIC have often produced higher response rates than DTIC alone, they also increased the toxicity without a significant improvement in survival compared to DTIC alone [89].

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