Cytotoxic chemotherapy for metastatic melanoma
- Jeffrey A Sosman, MD
Jeffrey A Sosman, MD
- Professor of Medicine
- Robert H. Lurie Comprehensive Cancer Center of Northwestern
Although the incidence of malignant melanoma is increasing, most cases are diagnosed at an early stage. Surgical excision is curative in most cases of early stage disease, and patients at high risk of developing metastatic disease may benefit from adjuvant therapy with interferon alpha or ipilimumab . (See "Initial surgical management of melanoma of the skin and unusual sites" and "Adjuvant immunotherapy for melanoma".)
Most patients with stage IV disease require systemic treatment (table 1A-B). For patients with extracranial metastatic melanoma, cytotoxic chemotherapy historically was widely used in patients who were not candidates for therapy with high-dose interleukin-2 (IL-2), although this approach was never demonstrated to improve survival. However, with the development of new immunotherapy approaches and targeted therapy for BRAF-mutated tumors, chemotherapy is now generally limited to second- or third-line settings and is frequently omitted altogether.
The clinical role of cytotoxic chemotherapy administered as a single agent, in combination chemotherapy regimens or in combination with biological agents (IL-2, interferon alfa [IFNa]), will be reviewed here. An overview of the management of advanced melanoma is presented separately. (See "Overview of the management of advanced cutaneous melanoma".)
CHOICE OF THERAPY FOR DISSEMINATED DISEASE
Approaches that have been shown to provide clinically important benefit for patients with disseminated melanoma in appropriately selected patients include immunotherapy with high-dose interleukin-2 (IL-2), immunotherapy with checkpoint inhibitors targeting CTLA-4 or programmed cell death protein 1 (PD1), and therapy targeting the MAP kinase pathway with BRAF and MEK inhibitors in patients whose tumors contain a V600 mutation in the BRAF gene (figure 1).
Cytotoxic chemotherapy does not have an established role in the management of patients with advanced melanoma. However, chemotherapy retains a role as therapy for patients whose disease can no longer be controlled with immunotherapy or targeted agents. Although chemotherapy has not been demonstrated to increase overall survival, combination regimens and single-agent chemotherapy have been associated with objective responses in a minority of patients. (See 'Combination regimens' below and 'Single-agent chemotherapy' below.)
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- CHOICE OF THERAPY FOR DISSEMINATED DISEASE
- SINGLE-AGENT CHEMOTHERAPY
- Dacarbazine and temozolomide
- - Dacarbazine
- - Temozolomide
- Platinum compounds
- Nanoparticle albumin bound paclitaxel
- Other agents
- COMBINATION REGIMENS
- Dacarbazine or temozolomide combinations
- Carboplatin paclitaxel
- Carboplatin paclitaxel bevacizumab
- IFNa or IL-2 biochemotherapy
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS