Managing Side Effects From EGFR Inhibitors
by Dr. C.H. Weaver M.D. 12/2018
Epidermal Growth Factor Receptor (EGFR) inhibitor drugs are a type of precision cancer medicine commonly used to treat lung, colon, head and neck and other cancers that over express the EGFR. There are several EGFR inhibitor drugs and these cause similar side effects.
The EGFR pathway is a normal biologic pathway found in healthy cells. It is involved in regular cellular division and growth. However, certain mutations within the EGFR gene can lead to an overactive EGFR pathway, leading to the development and/or spread of cancer. These cancers are referred to as EGFR-positive, and there are several FDA-approved medications to block the activity of EGFR and slow cancer growth for EGFR-positive cancers. EGFR mutations are most common in individuals who never smoked, woman, people of Asian ethnicity, and those with a type of lung cancer known as adenocarcinoma.
- Tagrisso (Osimertinib)
- Tarceva (Erlotinib)
- Erbitux (Cetuximab)
- Iressa (Gefitinib)
- Gilotrif (Afatinib)
- Vectibix (Panutumamab)
Unique side effects of all EGFR inhibitors include:
- Skin rash & Dry skin
- Finger or toenail infection
- Inflammation of mouth and lips (stomatitis)
- Loss of appetite
Skin rash: The most commonly seen side effect from EGFR inhibitors is a papulopustular skin rash that erupts most often on the face but can also be seen on the chest, back, trunk, and limbs. It tends to be associated with dry skin and at times can be diffuse and very disruptive. The rash commonly manifests in the first 1 to 2 weeks of treatment.
Other skin and hair side effects may include alopecia (hair loss), paronychias (nail damage), conjunctivitis, skin fissures, and generalized pruritus.
- Since the rash tends to be drying, applying a thick, emollient cream to the face and body once or twice a day as soon as the medication is started can be helpful. Creams tend to be better as lotions are usually thinner and water-based. Be sure that the cream is without dyes or fragrances that may irritate the skin.
- Patients who anticipate sun exposure should apply a sun block of SPF15 or higher.
- Another prevention technique is to take the oral EGFR inhibitors on an empty stomach. Taking them with food will increase their bioavailability, thus causing heightened side effects.
- If symptoms persist physicians typically utilize a step-wise approach based on severity of the rash. They will first use topical corticosteroids and antibiotics to treat a minor rash and may add oral antibiotics and oral corticosteroids if necessary for moderate or severe rashes.
With longer-term use of EGFR inhibitors, other dermatologic effects can occur.
Paronychias Inflammation and soreness around the nail bed is known as paronychias which can be difficult to treat.
· Topical antibiotics or antifungals, or soaks with Epsom salts or diluted betadinef can sometimes help.
· Oral antibiotics may work, especially if erythema or pus is present. Prevention is key.
· Keeping nails clean and trimmed can hopefully prevent this complication.
Fingertip splitting from very dry skin is also a later side effect. Prescription-strength urea moisturizers and glues such as Superglue or Liquid Bandaid can be utilized for treatment. Be sure to not exposing fingers to extreme temperatures or friction; this may exacerbate the splitting or paronychias.
Alopecia or hair thinning can occur from EGFR inhibitor use. The alopecia is usually partial rather than complete, as occurs with chemotherapy; however, the hair can become brittle and fall out in clumps. This side effect can be worse if the papulopustular rash is present on the scalp. Therapeutic shampoos, such as OTC t-gel shampoos or prescription-strength shampoos such as fluocinolone acetonide (Capex), can help moisturize the scalp. The eyelashes and eyebrows can also grow long and brittle, sometimes curling inward toward the eye. To avoid corneal abrasions, the eyelashes should be kept trimmed.
Diarrhea is another common side effect and can occur at any time during treatment with EGFR inhibitors. Other less common GI side effects can be nausea and vomiting, anorexia, and stomatitis.
Recommended dietary guidelines for diarrhea
· Patients should be advised to avoid spicy or greasy foods and to follow the BRAT (bananas, rice, applesauce, toast) diet if loose stools occur. OTC medications such as loperamide (Imodium) can relieve the diarrhea.
· Maintain adequate liquid intake and consumption of liquids at room temperature. Avoid beverages containing lactose, caffeine, or alcohol, and large quantities of hyperosmotic beverages (eg, fruit juice, sweetened fruit drinks)
· Drink enough fluids to replace what is lost in addition to the recommended daily amount. Replacement fluids should contain some sugar and salt (eg, broth, Gatorade®, soft drinks with some of the carbonation removed)
· Avoid foods that exacerbate diarrhea (eg, raw fruits and vegetables; whole grain breads; nuts; popcorn; skins; seeds; legumes; and greasy, fried, high-fat foods)
If OTC products are not effective, a prescription medication such as diphenoxylate/atropine (Lomotil) can offer stronger relief.
Reduction in EGFR inhibitor dose may be necessary if the diarrhea persists. A patient who is having persistent diarrhea should be monitored for electrolyte imbalances, such as low magnesium and potassium levels.