Skip to content

Melanoma/Skin Cancer Health Center

Font Size

Melanoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage IV and Recurrent Melanoma

continued...

AEs leading to dose interruptions occurred in 35% of patients in the trametinib group and 22% of those in the chemotherapy group. AEs leading to dose reductions occurred in 27% of patients receiving trametinib and 10% of those receiving chemotherapy. The most common AEs included rash, diarrhea, nausea, vomiting, fatigue, peripheral edema, alopecia, hypertension, and constipation. Central serous retinopathy and retinal-vein occlusion are uncommon, but serious, AEs associated with trametinib. On-study cutaneous SCCs were not observed.

Combinatorial therapy with signal transduction inhibitors

Resistance to BRAF inhibitors, in patients with BRAF V600 mutations, may be associated with reactivation of the MAP kinase pathway. Early phase II data with combinations of BRAF and MEK inhibitors have supported testing this combination in phase III trials, such as NCT01584648, NCT01597908, and NCT01689519.[32] Combination therapy to address other mechanisms of resistance (e.g., via activation of the PI3K/Akt pathway) are in early-phase trials.

Multikinase inhibitors

Sorafenib

The multikinase inhibitor sorafenib has activity against both the vascular endothelial growth-factor signaling and the Raf/MEK/ERK pathway at the level of RAF kinase. This agent had minimal activity as a single agent in melanoma and two large, multicenter, placebo-controlled, randomized trials of carboplatin and taxol plus or minus sorafenib showed no improvement over chemotherapy alone as either first-line treatment or second-line treatment.[33,34]

KIT inhibitors

Early data suggest that mucosal or acral melanomas with activating mutations or amplifications in c-KIT may be sensitive to a variety of c-KIT inhibitors.[35,36,37] Phase II and phase III trials are available for patients with unresectable stage III or stage IV melanoma harboring the c-KIT mutation.

Chemotherapy

The objective response rate to DTIC and the nitrosoureas, carmustine and lomustine, is approximately 10% to 20%.[2,38,39,40] Responses are usually short-lived, ranging from 3 to 6 months, though long-term remissions can occur in a limited number of patients who attain a CR.[38,40] A randomized trial compared IV DTIC with temozolomide (TMZ), an oral agent that hydrolyzes to the same active moiety as DTIC; OS was 6.4 months versus 7.7 months, respectively (HR, 1.18; 95% CI, 0.92–1.52). While these data suggested similarity between DTIC and TMZ, no benefit in survival has been demonstrated for either DTIC or TMZ and therefore, demonstration of similarity did not result in approval from the FDA.[3][Level of evidence: 1iiA] An extended schedule and escalated dose of TMZ was compared with DTIC in a multicenter trial randomly assigning 859 patients (NCT00091572). No improvement was seen in OS or PFS for the TMZ group, and this dose and schedule resulted in more toxicity than standard dose, single-agent DTIC.[41][Level of evidence: 1iiA]

1|2|3|4|5|6|7|8|9
Next Article:

Today on WebMD

Malignant melanoma
About 40-50 percent of those who live to be 65 may get it. Here’s how to spot early.
Woman checking out tan lines
There’s a dark side to that strive for beauty. See them here.
 
sauteed cherry tomatoes
Fight cancer one plate at a time.
Lung cancer xray
See it in pictures, plus read the facts.
 
12 Ways to Protect Your Skin from Melanoma
ARTICLE
precancerous lesions slideshow
SLIDESHOW
 
Do You Know Your Melanoma ABCs
VIDEO
15 Cancer Symptoms Men Ignore
ARTICLE
 
screening tests for men
SLIDESHOW
Vitamin D
SLIDESHOW
 
Is That Mole Skin Cancer
VIDEO
Brilliant sun rays
Quiz
 

WebMD Special Sections