Evidence included from outside the systematic review is identified with an asterisk (*) following the reference.
The historical standard for chemotherapy is single agent dacarbazine (DTIC) but response rates are only 5–15%, with only 0–2% complete responses and most responses are of short duration. Fotemustine and NAB-paclitaxel have slightly higher overall response rates compared with dacarbazine, but with no benefit in overall survival.* Unlike other single agents used in melanoma, fotemustine is associated with a higher risk of myelosuppression (i.e. reduced bone marrow activity resulting in decreased production of red blood cells, white blood cells and platelets).* The oral alkylating agent temozolomide has equivalent efficacy to dacarbazine (median survival 7.7 months vs 6.4, respectively). Combination chemotherapy does not improve survival over that of single agents and increases toxicity.* While it is recognised that chemotherapy is of palliative intent in patients with metastatic melanoma, there is no formal evidence that any form of chemotherapy improves duration or quality-of-life in this setting.
Evidence summary table
|Single agent fotemustine, dacarbazine or temozolomide can be used for palliation of patients with metastatic melanoma in patients who have progressed on other drug therapies.||II||, , , , |
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- Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012 Jul 28;380(9839):358-65 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22735384.
- Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015 Jan 22;372(4):320-30 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25399552.
- Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011 Jun 30;364(26):2507-16 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21639808.
- Hill GJ 2nd, Krementz ET, Hill HZ. Dimethyl triazeno imidazole carboxamide and combination therapy for melanoma. IV. Late results after complete response to chemotherapy (Central Oncology Group protocols 7130, 7131, and 7131A). Cancer 1984 Mar 15;53(6):1299-305 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/6362841.
- Avril MF, Aamdal S, Grob JJ, Hauschild A, Mohr P, Bonerandi JJ, et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol 2004 Mar 15;22(6):1118-25 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15020614.
- Hersh EM, Del Vecchio M, Brown MP, Kefford R, Loquai C, Testori A, et al. A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma. Ann Oncol 2015 Nov;26(11):2267-74 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26410620.
- Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000 Jan;18(1):158-66 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10623706.
- Eigentler TK, Caroli UM, Radny P, Garbe C. Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials. Lancet Oncol 2003 Dec;4(12):748-59 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14662431.