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Toxicities for therapies in Melanoma

Terms in this set (18)

Nivolumab
better efficacy and toxicity compared to ipilimumab

Preferred immunotherapy for adjuvant therapy of stage 3 completely resected disease
Ipilimumab
targets CTLA-4 on cytotoxic T cells
approved first line in unresectable and metastatic melanoma

increased disease free period and overall five year survival

Toxicities grade 3 or higher by over 40% of patients, 50% of patients had to discontinue due to toxicity
Ipilimumab Toxicites
can happen during treatment or several weeks after treatment is completed

2-3 weeks skin: rash, pruritus, vitiligo,

6-7 weeks Gi and liver: diarrhea, colitis, elevated enzymes, elevated bilirubin, hepatitis

>9 weeks Endocrine: hypophysitis, hypothyroidism
Ipilimumab toxicity management
Grade 1 and 2: symptom control continue therapy

Grade 3 and 4: hold therapy and treat with high dose steroids
Interferon Alfa
response rates are low 10-30%, but half of those who do respond have long disease free survival and potentially cure

high dose therapy improves survival for stage 2B/C with primary lesion >4mm or involving regional lymph nodes rendered disease free by surgery
Interferon Alfa Toxicities
fever
flu-like
severe fatigue
depression, suicidal ideation
hepatic toxicity
hematologic toxicity

no one finishes course of therapy
Dosed 5 times a day for 4 weeks
Dabrafenib/Trametinib
Indicated for completely resected stage 3 disease with BRAFV600 mutation and SLN metastasis ?1mm with BRAFV600 mutation

Toxicity: fevers, fatigue, nausea
T-VEC

Talimogene laherparepvec
genetically modified herpes simplex virus injected into lesion

Indicated for unresectable cutaneous, subcutaneous, and nodular lesions in patients with recurrent melanoma after initial surgery
T-VEC

Talimogene laherparepvec Toxicities
-Most resolved with 72 hours

-vasculitis, fatigue, chills, HA, cellulitis, NVD, bacterial infection, herpes virus infection, pain/inflammation at injection site, myalgia, arthralgia, flu-like, fever
Vemurafenib Toxicities
BRAFV600 mutation tested

works good for 6 months, then recurrence

Common: peripheral edema, fatigue, HA, rash/skin disorders, photosensitivity, NVD, arthralgia

Rare: QTc prolongation

Unique: development of squamous cell carcinoma
Dabrafenib Toxicities
BRAFV600 mutation tested

can be used as single agent or in combo with trametinib- always used in combo

combo better than vemurafenib alone
combo suppress downstream BRAF therapy resistance

HA, hyperkeratosis, hyperglycemia, hand foot syndrome, arthralgia, alopecia, squamous cell carcinoma
Trametinib Toxicities
-inhibits MEK activation, combo with BRAF mutation targeted therapy

-not for patients who have received previous BRAF inhibitor therapy

skin rash, diarrhea, anemia, increased LFT, hemorrhage, HTN, cardiomyopathy

decreased squamous cell carcinoma when combined with Dabrafenib
Cobimetinib Toxicities
Combo with vemurafenib

indicated in treatment of unresectable or metastatic melanoma in patients with BRAFV600 mutation

decreased ejection fraction, photosensitivity, decreased electrolytes, diarrhea, myelosuppresion, increased LFT, visual impairment, increased SCr

slight increase in toxicities with combo but decrease in squamous cell carcinoma
Pembrolizumab
binds PDL1

indicated in unresectable or metastatic melanoma

less toxicity and better DFS and OS than ipilimumab, 1st line in metastatic before ipilimumab
nivolumab/ipilimumab combo
indicated in untreated, unresectable stage 3 or metastatic stage 4 melanoma

adverse effects: fatigue, NVD, pruritus, rash, fever, decreased appetite, increased LFT, colitis, hypothyroidism
Chemo
single or combo rarely cures any metastatic disease
Interleukin 2
stimulates cytotoxic T cells

life-threatening capillary leak syndrome: hypotension, visceral edema, dyspnea, tachycardia, arrhythmias, acute renal failure

pt receive therapy in ICU
Dacarbazine (DTIC)
approved for use in metastatic melanoma, only chemo approved in melanoma
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