Dermatologic toxicity + Hormonal Flashcards
What kind of dermatologic toxicity do cytotoxic chemotherapy cause (4)
- Alopecia
- Acral erythema/ hand-foot syndrome
- Photosensitivity
- Hyperpigmentation
What kind of dermatologic toxicity do targeted therapies cause (5)
- Macular/papular rash
- Acral erythema/ hand-foot syndrome
- Acneinform EGFR rash
- Photosensitivity
- Keratocanthomas and squamous cell carcinoma
What kind of dermatologic toxicity do Immunotherapies cause (#)
- Dermatitis
- Alopecia areata
- Bullous pemphigoid
When does alopecia occur?
Temporary/permanent
7-14 days after treatment
Usually temporary
What is used for prevention in alopecia? When can it be used
Cold caps during chemo
- can only use for curative intent
Wide tooth combs + satin pillowcases
- reduces friction/damage to hair
Differentiate between Hand-foot Syndrome (HFS) and Hand-foot skin reaction (HFSR)
Area it affects
Causative agent
HFS
- Generalized, affects entire palms and soles
- Capecitabine (cytotoxic 5-FU type agent)
HFSR
- Localized, thickened area
- Pain, blistering, desquamation
- Sorafenib (targeted agent)
BOTH
- dryness, redness, numbness and tingling of palms and soles
How treat the following grading of HFS and HFSR
Grade 1
Grade 2
Grade 3
Grade 1
- Maintain dose level
Grade 2
- 1st appearance: interrupt therapy until resolved (for HFSR, reduce dose too)
- 2nd appearance: interrupt therapy until resolved, reduce dose
- 3rd appearance: interrupt therapy until resolved, reduce dose
- 4th appearance: D/C therapy
Grade 3
- 1st appearance: interrupt therapy until resolved, reduce dose
- 2nd appearance: interrupt therapy until resolved, reduce dose
- 3rd appearance: D/C therapy
What to treat sunitinib with HSFR
Interrupt dose for grade 3
- consider reducing dose or stretching out frequency
What are prevention methods of HFS and HFSR (5)
Prevention:
- Frequent moisturizing
- Avoiding sources of heat (washing dishes)
- Avoid friction (tight shoes, gardening)
- Topical diclofenac for capecitabine HFS
- 10-20% urea cream for HFSR prevention (prevents thickening)
Treatment of HFS and HFSR
Withhold causative agent
Ice packs (not if Xelox use oxaliplatin + Capecitabine)
Oral and topical pain relievers
Which cancer agent causes the most maculopapular rash
TKIs
What is the treatment for maculopapular rash
Grade 1: <10% BSA
Grade 2: 10-30% BSA
Grade 3: 30%+ BSA
Grade 1: <10% BSA
- Oral antihistamine (loratadine)
- Menthol cream
Grade 2: 10-30% BSA
- Same as grade 1
- Add a topical corticosteroid (clobetasol 0.05%)
Grade 3: 30%+ BSA
- Refer to a dermatologist
What does the EGFR rash present as?
Correlates with?
Onset?
- It is acneiform (acne mimicking)
- Correlates with efficacy
- Develops 8-10 days into treatment
What are the 4 rash phases of EGFR
Phase 1: Sensory disturbance with erythema (itch, redness) (week 0-1)
2 – papulopustular eruption (week 1-3)
3 – crusting (weeks 3-5)
4 – eythematotelangiectasias (weeks 5-8)
(red areas of blood vessels)
(lesions gone by 2 months)
Treatment for EGFR rash
Grade 1: <10% BSA
Grade 2: 10-30% BSA
Grade 3-4: 30%+ BSA
Grade 1
- continue same dose
- topical clindamycin 2% + HC 1% lotion for 4 weeks
Grade 2
- continue same dose
1. Topical clinda + HC lotion
2. AND minocycline/doxycycline 100mg BID for 4 weeks
Grade 3-4
- consider reducing dose
- Treat as grade 2
ADD 0.5mg/kg prednisone for 7-14 days
- if no improvement consider discontinuation
- rarely use isotretinoin in practice if does not work
What can be used for EGFR rash prophylaxis (2)
Monocycline/doxycyline 100-200mg daily
Topical hydrocortisone 1% once-BID
Nonpharm strategies for EGFR rash
- Thick, alcohol-free emollient cream on dry area
- Non irritating and alcohol free cleanser
- Sunscreen of SPF 15+ (with zinc oxide or titanium dioxide)
- Adequately hydrate
- Avoid HOT water
- Avoid tight-fitting clothing
Anti-itch: cool compresses + antihitamines
Make-up: ok to use concealer, remove makeup with cetaphil or neutrogena (mild cleanser)
What cancer agents is photosensitivity associated with (4)
Noted with:
- Methotrexate
- 5-FU
- Dacarbazine
- BRAF-inhibitors (especially if monotherapy or with MEK inhibitors)
Photosensitivitiy
Prevention (3)
Management (2)
Prevention
- Avoid sun exposure
- High SPF sunblock
- Cover all areas (even if exposed for a short-time)
Management
- topical steroids
- Cool compresses
Which class of cancer agent is associated with Keratoacanthomas (KA) and Squamous Cell Carcinoma (SCC)
BRAF inhibitors
Keratoacanthomas (KA) and Squamous Cell Carcinoma (SCC) treatment
Surgery
Which cancer class therapies cause immunotherapy rash (skin rash) (3)
- PD-1
- PD-L1
- CTLA-4
Immunotherapy rash treatment
Grade 1: <10% BSA
Grade 2: 10-30% BSA
Grade 3: 30%+ BSA
Grade 4: Skin sloughing (dead skin)
Grade 1
- Traimcinolone/Fluocinonide (mild steroids)
- Continue treatment
Grade 2
- Traimcinolone/Fluocinonide (mild steroids)
- Continue treatment
Grade 3
- HOLD agent
- Give PO or IV steroids (IV if severe)
- Derm consult
Grade 4
- D/C agent
- IV steroids
- Derm consult
What are common toxicity symptoms with anti-estrogenic agents (5)
- Hot flashes
- Arthralgias
- Nausea
- Fracture (with aromatase inhibitor)
- Vaginal dryness
What drugs are used to manage hot flashes
(4 classes)
Antidepressants (SSRIs/SNRIs):
- Citalopram
- Desvenlafaxine/Venlafaxine
- Paroxetine (Paroxetine should not be use with Tamoxifen for hot flashes)
Anticonvulsants: Gabapentin, Pregabalin
Antihypertensive: Clonidine (possible efficacy)
Alternative therapy: Relaxation training, hypnosis (possible efficacy)
Management of Arthralgias (4)
Duloxetine
Other options (less evidence): Exercise, acupuncture
Supplement: Omega-3 fatty acid (for obese patients)
Short break/switching agents:
- SWITCHING anastrozole -> letrozole has relieved arthralgia for some
Management of Vaginal dryness
Replens gel
- topical estrogen safety debated
What ADRs are associated with Abiraterone (CYP17a inhibitor) (2)
Mineralcorticoid in nature
- Hypertension
- Hypokalemia
- Edema
Liver toxicity
How to treat the following abiraterone ADRs
Mineralcorticoid ADR
Liver toxicity
Mineralcorticoid ADR
- Prednisone 10mg daily
Liver toxicity
- Grade 3 elevation in AST/ALT or Bilirubin:
= HOLD + reduce to 500mg/day once LFTs return to baseline
- Grade 4 elevation in AST/ALT or Bilirubin:
= STOP Abiraterone
What are the ADRs of androgen deprivation therapy (4)
- Hot flashes
- Loss of libido and ED
- Fatigue
- Mood changes
Androgen-deprivation management..
Hot flashes (3)
Loss of libido and ED (2)
Fatigue (2)
Mood changes (1)
Hot flashes (3)
- Venlafaxine
- Gabapentin
- Clonidine
Loss of libido and ED (2)
- Exercise and healthy lifestyle change
- Medical therapies (caverject, vacuum pump)
(VIAGARA does not work here)
Fatigue (2)
- Exercise (even a 10-min walk is important)
- Methylphenidate
Mood changes (1)
- Depression screening
Differentiate between MOA of the checkpoint inhibitors
CTLA-4i
PD-1i
PD-L1
CTLA-4i
- T-cell primer
PD-1i
- Prevent T-cell inhibition
- work on receptor
PD-L1
- Prevent T-cell inhibition
- work on ligand
ADRs of checkpoint inhibitors (5)
Which drug is the worst?
- Rash/pruritis (managed with steroids)
- Enterocolitis (both small and large intestine)
- Hepatotoxicity
- Pneumonitis (alevoli inflammation)
- Endocrinopathy
(in order of onset of presentation)
Ipilimumab is more pronounced
- CTLA-4i
Immune-related dermatitis (rash) treatment
Grade 1-2 (30% or less)
Grade 3: (30%+)
Grade 4: (30%+ life-threatening)
Grade 1-2:
- CONTINUE agent
- Sun safety, moisturizer, mild soap,
- Topical steroids
- Diphenhydramine (benadryl) (antihistamine)
Continue for 1-2 weeks - if no improvement, HOLD agent + start PO steroid-> taper
Grade 3:
- HOLD agent
- PO or IV steroid -> taper
Grade 4: STOP agent
- PO or IV steroid -> taper
T/F immune-mediated colitis can present without diarrhea
True
Management of Enterocolitis
Grade 1: <4 stools/day
Grade 2: 4-6 stool/day
Grade 3: 7+ stools/day
Grade 4: Life-threatening colitis, perforation
Grade 1:
- CONTINUE agent
- antidiarrheal management
Grade 2:
- HOLD agent
- Antidiarrheal management.
- If persists past 3-5 days start PO steroid
Grade 3:
- HOLD agent
- Prednisone PO (unless bowel perforation)
- If no improvement in 5 days (or recurrence), intensify with infliximab
Grade 4: STOP agent
- Prednisone PO (unless bowel perforation)
- If no improvement in 5 days (or recurrence), intensify with infliximab
How to manage immune-related hepatitis?
Define
Grade 2
Grade 3-4
Grade 2:
- AST/ALT 3-5x ULN OR total bilirubin 1.5-3x ULN
- HOLD agent, reassess in 5-7 days
- If no improvement, Prednisone PO
Grade 3-4:
- AST/ALT >5x ULN OR total bilirubin >3x ULN OR significant increase with liver metastases
- STOP therapy, start prednisone PO -> taper
- If no improvement in 5-7 days, consider non-steroid immunosuppressive (mycophenolate)
What are the types of immune-related endocrinopathies (3)
Hypophysitis (inflammation of pituitary gland):
- Headache at first
- then confusion, hallucination, impaired vision, hypotension, impotence (altered mental state)
Hypothyroidism:
- (fatigue, cold feeling, etc..)
Adrenal toxicity:
- hypotension, hypoglycemia
- vomiting, weight loss, pigmentation
- hypokalemia, hyponatremia
Enddocrinopathy treatments
- Asymptomatic TSH
- Symptomatic endocrinopathy
- Suspicion of adrenal crisis
Asymptomatic TSH elevation:
- Continue therapy, monitor
Symptomatic endocrinopathy:
- HOLD (don’t stop) treatment + PO steroids
- Hormone replacement if needed (based on labs/pituitary scan)
Suspicion of adrenal crisis:
- HOLD (don’t stop) treatment-> IV steroids + IV fluids
How does immune-related pneumonitis present?
- SOB
- Dry cough
- inc O2 requirements
- can detect on imaging (can be asymptomatic)
What are risk factors for pneumonitis (5)
- NSCLC (lung cancer) with chronic lung inflammation
- Heavily pretreated patients
- Combination of CTLA-4 and PD-1 agents
- Prior lung radiation
- History of COPD
Treatment of immune related pneumonitis
Grade 1: (radiographic changes only)
Grade 2: (mild-mod sx)
Grade 3-4: (severe)
Grade 1:
- Consider HOLDING agent
- monitor Q2-3 days
Grade 2:
- HOLD agent
- PO prednisone + lung testing/scans
Grade 3-4:
- STOP agent
- PO prednisone + Prophylactic ABX
- If worsening after 2 days, consider non-steroid immunosuppressive agents (infliximab, cyclophosphamide, mycophenolate)
