Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
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Volume 8, Number 2, February 2016, pages 63-75

Novel Drugs and Combination Therapies for the Treatment of Metastatic Melanoma


Figure 1.
Figure 1. Overview of the signal transduction pathway like mitogen-activated protein kinase/extracellular signal-regulated kinases signaling pathway.


Table 1. Adverse Effects of Immunotherapy and Management
Treatment related adverse effectsGrade 1Grade 2Grade 3Grade 4
AST: aspartate aminotransferase; ALT: alanine aminotransferase; ULT: upper limit of normal.
Skin toxicity.
Most common adverse effect.
Mild to moderate localized rash or pruritus; papules/pustules covering < 10-30% of body surface.
Rx: topical corticosteroids.
Non-localized rash (diffuse, ≤ 50% of skin surface)
Rx: topical corticosteroids and monitoring.
Intense or widespread rash > 30%; skin sloughing < 10-30% of body surface; epidermal or mucus membrane detachment.
Rx: systemic corticosteroids, hospitalization and hold immunotherapy.
Stevens-Johnson syndrome, toxic epidermal necrolysis (1% of cases), or rash complicated by full-thickness dermal ulceration, bullous and blisters.
Rx: immediate hospitalization, systemic steroids and discontinue drug permanently.
GI toxicity/diarrhea.
Second most common
< 4 stools per day over baseline
Rx: symptomatic treatment.
4 - 6 stools per day over baseline.
Rx: IV fluids for < 24 h, and symptomatic treatment.
Rule out infectious causes.
If not improving, hold drug and consider oral/IV steroids.
≥ 7 stools per day over baseline.
Rx: IV fluids for > 24 h, hospitalization and IV steroids.
Life-threatening consequences (e.g., hemodynamic collapse).
Rx: hospitalization, IV fluids, IV steroids.
If symptoms not improving with IV steroids, consider infliximab.
Occurs in about 10% of patients.
Asymptomatic or mild symptoms.
Rx: clinical or diagnostic observations only; intervention not indicated
AST or ALT > 2.5 to ≤ 5.0× ULN and/or total bilirubin > 1.5 to ≤ 3.0× ULN.
Rx: frequent monitoring of LFTs.
Consider holding immunotherapy.
AST or ALT > 5× ULN and/or total bilirubin > 3.0× ULN.
Rx: hold immunotherapy and frequent monitoring of LFTs.
Rule out viral, autoimmune or drug induced hepatitis.
High ammonia levels and hepatic encephalopathy.
Rx: discontinue drug permanently and start high dose steroids (2 mg/kg/day).
If not improving in 48 h, consider oral mycophenolate (500 mg twice daily).
Endocrine toxicity.
Occurs in 4-8% of patients.
Rx: clinical or diagnostic observations only; intervention not indicated
Moderate symptoms.
Rx: if suspicious for hypophysitis is high, complete endocrine workup should be done.
Hormone replacements may be considered.
Severe symptoms.
Rx: hospitalization indicated.
Stop immunotherapy.
Short course of steroids may improve pituitary function.
Adrenal crisis: severe dehydration, hypotension, or shock. Life-threatening consequences
Rx: high dose IV steroids.