The History and Future of Chemotherapy for Melanoma

Abstract

Melanoma is considered a chemotherapy-resistant tumor, but in fact several chemotherapeutic agents show single-agent activity at the level of 10% to 15%, similar to the efficacy of the chemotherapeutic armamentarium used against other tumor types. Several combination chemotherapy regimens have been tested, but no survival benefit has been demonstrated. Few of these trials have been compared with standard dacarbazine (DTIC) in an adequately powered randomized trial, and even the largest of these trials were only powered to detect unrealistically large improvements in overall survival. In this article, the authors review past chemotherapy trials and the current state of chemotherapy for melanoma. Looking to the future, the authors are encouraged by recent observations that the addition of sorafenib to DTIC (or temozolomide) can increase response rates and survival. The authors suggest that this could form the core on which additional active chemotherapeutic drugs could be added with the hope of developing a regimen that improves overall survival. This paradigm of stepwise addition of active chemotherapeutic drugs has been successful in the development of chemotherapy regimens that improve survival in other solid tumor systems. In colon carcinoma, for example, the current regimens were built on fluorouracil (5FU)/leucovorin, which has similar activity to DTIC in melanoma. This could serve as a model for studies on melanoma.

Genetic factors in metastatic progression of cutaneous melanoma: the future role of circulating melanoma cells in prognosis and management

“…Mortality rates continue to remain high, due mainly to progression of multiple drug resistant metastases for which the cure rate is currently less than 20% [5,6]. Much effort has been put into identifying prognostic factors that correlate with clinical outcomes to enable The American Joint Committee on Cancer (AJCC) to devise an accurate TNM clinical staging system.…”

Effects of nivolumab in peritoneal carcinamatosis of malign melanoma in mouse model

“…5-year survival less than 5% patients with metastatic disease, and a median survival is 3-8 months [8][9][10] . Melanoma cells resistant to chemotherapy, but DTIC is the standard chemotherapeutic agent for years with 15% avarage response and extend survival to 10 months 11 . Despite current NCCN guidelines, many oncology units still apply DTCI alone or combination with other agents in clinical practice 12 …”

Ileocecal Intussusception Secondary to Bowel Metastases from Cutaneous Melanoma: Case Report

“…17 There are no effective chemotherapy regimens for prolong the survival of metastatic melanoma, but some agents may control the disseminated disease, reduce the local recurrence and improve the quality of life. 18 The most appropriate diagnostic method to show the intussusception is contrast enhanced CT with a diagnostic accuracy of 58-100%. 19 All evidences of intestinal obstruction could be seen in our case and also CT images revealed intestinal intussusception and dilatation of proximal small intestine.…”