Dose Interruption or Modification

Dose Interruption or Modification

PEP Topic 
Skin Reactions

Dose interruption or modification involves delay in planned treatment or reduction in treatment dosages. This is generally done in response to treatment-related toxicities.

Likely to Be Effective

Guideline/Expert Opinion

Burtness, B., Anadkat, M., Basti, S., Hughes, M., Lacouture, M.E., McClure, J.S., . . . Spencer, S. (2009). NCCN Task Force Report: Management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. Journal of the National Comprehensive Cancer Network, 7(Suppl. 1), S5–S21.


Purpose & Patient Population:

To describe commonly used therapies that National Comprehensive Cancer Network (NCCN) Task Force members agreed are appropriate standards of care to manage dermatologic and ocular toxicities that occur in patients with cancer being treated with epidermal growth factor receptor (EGFR) inhibitors.

Type of Resource/Evidence-Based Process:

NCCN Task Force members reviewed available published data on treating toxicities associated with EGFR inhibitors, reviewed data from the treatment of clinically similar toxicities from different etiologies, and shared their expert opinions. Through this process, they developed recommendations for managing dermatologic and ocular toxicities associated with EGFR inhibition in patients with cancer. 

The databases searched were not identified specifically. The authors stated their recommendations were supported only by anecdotal evidence.

Search keywords, inclusion criteria, and exclusion criteria were not provided.

Phase of Care and Clinical Applications:

  • Patients were undergoing the active treatment phase of care.
  • The study has clinical applicability to late effects.

Guidelines & Recommendations:

Modifying EGFR Inhibitor Therapy

  • Brief dosing interruptions can be helpful in managing high-grade EGFR-inhibitor–associated skin and ocular toxicities. These toxicities may lessen over the course of one to two weeks, and then reintroduction of the EGFR inhibitor often is feasible.
  • The role of dose reduction remains uncertain. The reproducible relationship between rash and survival for all EGFR antagonists suggests, but does not prove, that maintaining full dose in patients with rash may be beneficial.

Topical Therapies for Rash

Prophylactic/Mitigating Treatments:

  • Long-term prophylactic topical mupirocin ointment can be used in the nose to prevent Staphylococcus aureus colonization, especially for patients with recurrent infection.

Reactive Treatments: 

  • Topical steroids (low-strength on the face; medium strength on the body) and topical antibiotics (e.g., clindamycin, erythromycin) are based on expert reference and clinical experience, rather than data from randomized clinical trials.
  • Petroleum jelly, ammonium lactate, or dilute hydrogen peroxide soaks with gentle debridement may remove excessive formation of yellow crusts and debris in severe skin rash.
  • If superinfection is suspected (because of excessive induration and erythema, the presence of a dominant lesion that appears larger and more inflamed than the remainder of the lesions, or purulent drainage), then the site should be cultured to determine the organism and sensitivity. Positive cultures may be evidence of infection or colonization, and clinical judgment is needed to evaluate culture results.
  • Pulsed dye laser and intense pulsed light may effectively decrease the erythema and prominence of telangiectatic vessels (dilated blood vessels).
  • Postinflammatory hyperpigmentation may fade through the use of hydroquinone, azelaic acid, topical retinoids, or laser-based therapies.

Systemic Therapies for Rash

Prophylactic/Mitigating Treatments:

  • These treatments are used to decrease the severity of rash.
  • Oral antibiotics include tetracycline (500 mg BID), minocycline (100 mg daily), and doxycycline (100 mg BID).
  • Multiagent prophylactic skin treatment (Skin Toxicity Evaluation Protocol With Panitumumab [STEPP] study—randomized trial) includes oral doxycycline (100 mg BID), topical corticosteroids (1% hydrocortisone), skin moisturizer, and sunscreen.
  • Sunscreens that are non–alcohol based and physical sunblocks (e.g., zinc oxide, titanium dioxide) with 30 sun protection factor (SPF) that block ultraviolet A (UVA) and ultraviolet B (UBV) light should be applied thickly. 
  • A topical vitamin K3 analog, menadione, is being investigated in a phase 1 trial for use in reducing the skin rash associated with EGFR inhibitors.

Reactive Treatments:

  • The following treatments are based on anecdotal reports or nonrandomized studies.
    • Oral antibiotics:  tetracycline, minocycline, and doxycycline
    • Retinoids:  isotretinoin (problem with paronychia) and low-dose acitretin (oral 10 mg per day)
    • Systemic steroids: May be appropriate in some settings (usually in the inpatient setting) with careful supervision.


  • For bacterial and fungal cultures, treat infection with appropriate oral antibiotics.
  • Apply Monsel’s (ferric subsulfate) solution or silver nitrate to bleeding, overgrown tissue.
  • Soaks for symptomatic relief include 4% thymol in alcohol, aluminum acetate (Burow's solution), white vinegar (1:10), and bleach (1/4 cup bleach: 3 gallons water).
  • Use topical corticosteroid cream (e.g., methylprednisolone) for inflammatory, noninfected paronychia.
  • Clip nails, remove embedded nails or possibly the nail plate, and pack the area with cellulose sponge (Surgifoam®).
  • Wear well-fitted shoes or sandals.
  • Cushion nail beds for symptomatic comfort.
  • Use topical corticosteroid cream (e.g., methylprednisolone) for inflammatory paronychia.


  • Apply cool compresses, sedating antihistamines (diphenhydramine) at evening or bedtime, topical steroids, and topical menthol lotions.
  • Give oral gabapentin or pregabalin (100 mg BID).
  • For dry skin, minimize the use of soap, increase use of emollients, avoid alcohol-based agents and topical antipruritics (e.g., Aveeno® Anti-Itch, Sarna® Ultra).
  • Topical agents for the scalp include fluocinonide 0.05%, clobetasol foam, or steroid shampoo.


  • Frequently apply zinc oxide (30%), petroleum jelly, and other thick emollients (e.g., Aquaphor®, Aveeno, Bag Balm®, Cetaphil®, Cutemol®, Eucerin®, Vanicream®).
  • Avoid alcohol-based lotions, antibacterial soaps, long baths or frequent water immersion, and contact with harsh chemicals.

Fissuring on the heels or fingertips:

  • Do not use Monsel’s solution (ferric subsulfate) on the face. Some NCCN Task Force members believed this solution may increase the size of the fissures and stain tissue.
  • Silver nitrate
  • Aluminum chloride solution
  • Zinc oxide cream (20%–30%)
  • Bleach soaks (10 minutes per day) to prevent infection (1/4 cup bleach: 3 gallons water)
  • Protective coverings
  • Apply cyanoacrylate glue (e.g., Krazy Glue®, Super Glue®) to fissures to relieve pain and promote healing. Some patients and healthcare providers prefer cyanoacrylate glue because liquid cyanoacrylate coverings may increase the sensation of burning and delay healing.
  • Antibiotics (e.g., doxycycline) for infected fissures


  • Petroleum jelly or other thick emollients (e.g., Bag Balm)
  • Mild (neutral pH) soap
  • 12% ammonium lactate, 6% salicylic acid, and 20% urea

Nursing Implications:

The NCCN Task Force report described the management of dermatologic and ocular toxicities that occur in patients receiving EGFR inhibitors. Few recommendations were evidence based; however, some commonly used therapies have data supporting their use. 

Implications for nursing practice include integrating the recommendations of the NCCN Task Force into facility algorithms for preventing or managing several types of EGFR-induced skin reactions. Well-designed research is needed in this area.

Edmonds, K., Hull, D., Spencer-Shaw, A., Koldenhof, J., Chrysou, M., Boers-Doets, C., & Molassiotis, A. (2012). Strategies for assessing and managing the adverse events of sorafenib and other targeted therapies in the treatment of renal cell and hepatocellular carcinoma: Recommendations from a European nursing task group. European Journal of Oncology Nursing, 16, 172–184.

PROFESSIONAL GROUP: Nursing task group; no formal association or description of how the group was brought together was described.


Purpose & Patient Population:

PURPOSE: To review effective strategies to assist nurses in caring for patients receiving sorafenib, with the focus on those adverse effects the group felt were most difficult to manage—hand-foot syndrome, diarrhea, fatigue, and oral complications

TYPES OF PATIENTS ADDRESSED: Patients receiving sorafenib for renal cell or hepatocellular cancer

Type of Resource/Evidence-Based Process:

RESOURCE TYPE: Evidence-based guideline

DATABASES USED: PubMed, Cochrane Library, and hand-searching of the Clinical Journal of Oncology Nursing and American Society of Clinical Oncology website     

KEYWORDS: Side effect general terms, and specific terms for each side effect (e.g., altered taste, hand-foot syndrome); disease-related search terms included renal cancer, cancer of the kidneys, hepatocellular carcinoma, and liver cancer

INCLUSION CRITERIA: Evidence base included wider literature regarding the management of similar adverse events in patients with other types of cancer and other types of antitumor therapy. No other specific criteria were stated.


Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment            
  • APPLICATIONS: Late effects and survivorship

Results Provided in the Reference:

Out of 2,469 initial citations retrieved, 37 were included for review. No specific quality evaluation of citations was done due to the nature of the literature, with few clinical trials. No description of the group process used is provided. Findings from citations reviewed were outlined and a review of the literature was provided, but no actual synthesis of evidence exists. Noted is that most evidence in this area is from experience.

Guidelines & Recommendations:

Recommendations for mucositis include oral care, amifostine, and antibiotic paste for prophylaxis. For symptom management, recommendations include ice chips, topical lidocaine solutions, sage tea and baking soda oral rinses, and topical solution containing aloe vera, and advising patient to avoid tobacco, alcohol, and spicy foods, mucosal coating agents (e.g., Gelclair®), hydrolytic enzymes, and treatment interruption. For diarrhea, recommendations are patient education, loperamide, diphenoxylate, cholestyramine, probiotics, tincture of opium, and antidiarrheal agents, and avoidance of lactose, high roughage, fatty and spicy foods, fruit juice, and caffeine. For hand-foot syndrome, recommendations include use of emollients, wearing gloves, and avoiding constrictive footwear, hot water, urea- or salicylate-containing creams, and treatment interruptions. For fatigue, recommendations include encouraging activity, maintaining normal work and social schedules, providing supportive care, and considering antidepressants, methylphenidate, sleep medication, and treatment-free intervals.


This review adds nothing new to the limited body of evidence in this area, and does not include a huge body of literature related to the management of fatigue and diarrhea symptoms. Most evidence reviewed was of low quality and expert opinion. No process by which the group evaluated the evidence strength in order to make full recommendations is described, and the result is generally a listing of previously documented opinions related to the management of these symptoms.

Nursing Implications:

This review provides recommended assessments and management approaches that are at the level of expert opinion only.

Grunwald, V., Kalanovic, D., & Merseburger, A.S. (2010). Management of sunitinib-related adverse events: An evidence- and expert-based consensus approach. World Journal of Urology, 28, 343–351.

doi: 10.1007/s00345-010-0565-z

Purpose & Patient Population:

To provide advice for patient care in daily practice regarding the management of side effects of sunitinib.

Type of Resource/Evidence-Based Process:

Information was compiled and clinical experts were asked to identify the degree to which they agreed or disagreed with the information. Those measures agreed on by 70% of respondents were included in this summary. Clinicians had to have cared for at least 30 patients receiving sunitinib. Twelve German clinical experts provided analysis.

Databases searched were PubMed, Embase, Current Contents, and recommendations of oncology societies.

Key topics were sunitinib and tyrosine kinase inhibitor therapy management recommendations.

Guidelines & Recommendations:

Arterial Hypertension:

  • Mandatory blood pressure monitoring is recommended as often as daily. No clear recommendations exist for monitoring or optimal treatment with antihypertensives. The exact mechanism of effect is unclear, and hypertension may resolve during regular two-week pauses in treatment and reappear with continuation of therapy.
  • Agreement was reached on routine exercise, weight control, a sodium-restricted diet, and decreased alcohol consumption.


  • Maintain normal social and physical activity.
  • Balance work and sleep schedules.
  • Get moderate exercise.
  • Measure body weight routinely.
  • Use distraction (e.g., reading).
  • Offer medical treatment for secondary causes such as hypothyroidism, depression, anemia, or pain.
  • Consider reduction of sunitinib in cases with reduced quality of life.

Mucositis/Oral Disorders:

  • Avoid irritating food or drinks, such as spicy, acidic, very hot or cold, and dry or hard foods.
  • Use lip protection.
  • Oral hygiene is important.
  • Use of dexpanthenol lozenges and ointment is appropriate for mucosal protection.  
  • Oral symptoms should be treated with topical anesthetics, steroids, or anti-infectives.
  • In case of pronounced symptoms, consider interruptions of sunitinib.


  • Advise patients to split food and drinks into small amounts.
  • Avoid spicy or fried food and large amounts of fruits and vegetables.
  • Maintain sufficient fluid intake.
  • Avoid use of laxatives.
  • In cases of severe diarrhea, provide IV fluid and electrolytes.  
  • Early treatment with agents such as loperamide is advised.
  • Interruption or dose reduction of sunitinib was considered appropriate for grade 3 or 4 diarrhea only.

Nausea and Vomiting:

  • Eat a bland diet with small servings.
  • Use antiemetic drugs such as dopamine agonists and proton-pump inhibitors.
  • Sunitinib dosage may be reduced 12.5 mg in cases of grade 3 or 4 symptoms, or if symptom interventions are not successful.

Skin Reactions

Hand-Foot Syndrome:

  • Protect the hands and feet from heat and hot water.
  • Use cold packs for pain relief.
  • Apply moisturizers daily.
  • Use systemic anti-inflammatory medication in some cases.
  • Use topical antifungals for localized superinfection.
  • Use oral ibuprofen or paracetamol for pain control.
  • For grade 2 symptoms, consider break-in sunitinib.
  • For grade 3 symptoms, interrupt treatment temporarily and use lower doses after symptoms have resolved to lower than grade 1.

Erythema, Dry Skin, and Dermatitis:

  • Prevent sun exposure and use ultraviolet (UV) protective lotions with 15 to 30 sun protective factor (SPF).
  • Avoid irritating care products.
  • Use fatty creams or ointments after showering daily.
  • Limit sunitinib dose alterations as much as possible. Only 66% agreement was reached that a treatment break should be considered with grade 2 to 4 skin toxicity.


  • Experts were from a single setting, and one author was employed by Pfizer.
  • Recommendations were based on the opinion of a few experts, who had limited patient experience with sunitinib. The association with varied levels of evidence to support these recommendations is not evident.
  • Advice for patients and physicians was built mainly from the opinions of experts, rather than supporting data from controlled trials.

Nursing Implications:

A significant need exists for more scientific evidence on the prevention and management of side effects caused by these agents for cancer treatment.

Pinto, C., Barone, C.A., Girolomoni, G., Russi, E.G., Merlano, M.C., Ferrari, D., Maiello, E. (2011). Management of skin toxicity associated with cetuximab treatment in combination with chemotherapy or radiotherapy. Oncologist, 16, 228–238.

doi: 10.1634/theoncologist.2010-0298

Purpose & Patient Population:

To identify appropriate prophylactic and therapeutic interventions for the assessment and management of skin toxicities including rash, dryness, pruritus, paronychia, hair abnormality, and mucositis in patients with cancer receiving treatment including epidermal growth factor receptor inhibitors (EGFR-Is) (e.g., cetuximab) alone or in combination with chemotherapy or radiotherapy.

Type of Resource/Evidence-Based Process:

In the absence of definitive evidence from clinical trials, a group of Italian expert clinicians produced recommendations for skin toxicity management in patients receiving EGFR-Is. The RAND Corporation/University of California, Los Angles (UCLA) Appropriateness Method was used for obtaining consensus on the expert opinions.

The consensus panel comprised an advisory board of nine expert clinicians from different clinical settings (six medical oncologists, two radiation oncologists, and one dermatologist). A group of 40 panelists was identified.

The database searched was MEDLINE (2005 to October 2009). Potentially relevant abstracts presented at annual meetings or gastrointestinal symposia of the American Society of Clinical Oncology and the European Society of Medical Oncology were examined.

Search keywords were EGFR inhibitors, cetuximab, skin toxicity, skin rash, and radiation dermatitis.

Studies were included in the review if they were

  • In English language
  • Observational, prospective studies about assessment and treatment
  • Randomized, double-blind, placebo-controlled, or uncontrolled
  • Retrospective and uncontrolled
  • Systematic reviews and meta-analyses
  • Consensus guidelines
  • Reporting on available data for drugs tested in phase 3 (including abstracts).

Studies were excluded if they were published before 2005.

Phase of Care and Clinical Applications:

Patients were undergoing the active treatment phase of care.

Guidelines & Recommendations:

General Prophylactic Measures Before Starting Cetuximab Treatment:

  • Perform medical history and full-body skin evaluation with attention to xerosis, atopic dermatitis, and severe acne vulgaris.
  • Education and general interventions may include the following.
    • Use sunscreens.
    • Avoid habits or products that can produce dry skin (e.g., hot water, alcohol-based cosmetics).
    • Enhance skin hydration (e.g., use bath oils).
    • Use alcohol-free moisturizing creams frequently.
    • Use tocopherol oil or gel.
    • Avoid tight shoes.
    • Avoid excessive beard growth, shaving with a regular shaving razor (e.g., sharp multiblade), using pre–shaving cream emollients and moisturizing aftershave, using alcohol and aftershave, or using an electric razor.


Management of Grade 1 Skin Rash (Adapted From the National Cancer Institute [NCI] Common Toxicity Criteria [CTC], Version 3):

  • For skin lesions and symptoms including papules, pustules, or symptom-free erythema, do not modify cetuximab dose, interrupt treatment, or use topical or systemic treatment.
  • Administer general educational and prophylactic measures.

Management of Grade 2 Skin Rash:

  • Skin lesions include eruption with papules (grade 2A) or pustules (grade 2B) covering less than 50% of the body surface, with moderate symptoms and that do not interfere with daily activities.
  • Do not modify cetuximab dose or interrupt treatment.
  • Topical treatments include the following.
    • Antibiotics: clindamycin 1% gel, erythromycin 3% gel or cream, and metronidazole 0.75%–1% cream or gel, BID until improvement to grade 1.
    • Avoid benzoyl peroxide products.
    • Use erythromycin 2% lotion for lesions of the scalp.
  • Systemic treatments include the following.
    • Prevalence of pustules (grade 2A): No systemic treatment is recommended.
    • Prevalence of pustules (grade 2B): Antibiotics include oral semisynthetic tetracyclines. Use minocycline or doxycycline 100 mg orally once per day for more than four weeks and until the rash is asymptomatic.

Management of Grade 3 Skin Rash:

  • Skin lesions and symptoms include eruption with papules (grade 3A) or pustules (grade 3B) covering more than 50% of the body surface, with severe symptoms that interfere with daily activities.
  • Cetuximab dose modification or treatment interruptions include the following.
    • First occurrence: Delay cetuximab infusion for less than 21 days until the skin rash improves to grade lower than 2. If the rash improves, continue at 250 mg/m2. If the rash does not improve, discontinue therapy.
    • Second occurrence: Delay cetuximab infusion for less than 21 days until the skin rash improves to lower than grade 2. If the rash improves, continue at a reduced dose of 200 mg/m2. If the rash does not improve, discontinue therapy.
    • Third occurrence: Delay cetuximab infusion for less than 21 days until the skin rash improves to lower than grade 2. If the rash does not improve, continue at a reduced dose of 150 mg/m2. If the rash still does not improve, discontinue therapy.
    • Fourth  occurrence: Discontinue therapy definitively.    
  • Topical treatment:
    • Antibiotics: Use clindamycin 1% gel, erythromycin 3% gel or cream, and metronidazole 0.75%–1% cream or gel BID until improvement to grade 1. Avoid benzoyl peroxide products. 
    • Use erythromycin 2% lotion for lesions of the scalp.
  • Systemic treatment:
    • Antibiotics include oral semisynthetic tetracyclines. Use minocycline or doxycycline 100 mg orally once per day for more than four weeks and until the rash is asymptomatic.
    • Corticosteroids: Use methylprednisolone 0.4 mg/kg orally or prednisone 0.5 mg/kg orally for up to 10 days.
  • Systemic treatment for grade 3, highly symptomatic or nonresponsive patients:
    • Retinoids: isotretinoin 0.3–0.5 mg/kg orally
    • Corticosteroids: methylprednisolone or dexamethasone via IV
    • Antihistamines: clorfenamine intramuscularly (IM) or via IV
    • Antibiotics: amoxicillin or clavulanic acid and gentamicin via IV

Management of Grade 4 Skin Rash:

  • Skin lesions include generalized rash with severe symptoms that require emergency treatment.
  • Discontinue therapy immediately and definitively.
  • Topical treatment:
    • Antibiotics: Use clindamycin 1% gel, erythromycin 3% gel or cream, and metronidazole 0.75%–1% cream or gel BID until improvement to grade 1. Avoid benzoyl peroxide products.
    • Use erythromycin 2% lotion for lesions of the scalp.
  • Systemic treatment:
    • Retinoids:  isotretinoin 0.3–0.5 mg/kg orally
    • Corticosteroids:  methylprednisolone or dexamethasone via IV
    • Antihistamines: chlorpheniramine IM or via IV
    • Antibiotics: amoxicillin or clavulanic acid and gentamicin via IV
    • Hydration via IV
    • Hospitalization

Xerosis, Fissures, and Eczema


  • General educational and prophylactic measures are important.
  • Regular use of emollient ointments, almond oil, and preparation of polyethylene glycol is recommended.


  • For eczema, use topical treatment with medium-potency corticosteroids for one to two weeks.
    • Betamethasone dipropionate 0.05%–0.1% cream
    • Clobetasone 0.05% cream
    • Ointment fluocinolone acetonide
    • Hydrocortisone butyrate 0.1% cream
    • Consider simple or occlusive dressing for the extremities.
    • Topical antibiotic is recommended for superinfection.
      • Fusidic acid 2% cream
      • Bacitracin cream
      • Mupirocin 2% cream



  • Avoid friction and pressure on the nail fold (e.g., avoid tight shoes).


  • Wash with antiseptics including diluted hydrochloric acids solution or boric acid solution 3%.
  • Use creams containing corticosteroids and antiseptics.
    • Betamethasone 0.05% plus clioquinol 3% ointment
    • Betamethasone 0.1% plus gentamicin 0.05% cream
    • Betamethasone 0.1% plus gentamicin 0.1% cream
    • Betamethasone valerate 0.1% plus fusidic acid 2% cream
    • Triamcinolone acetonide 3% plus chlortetracycline 0.1% ointment
    • Triamcinolone benetonide 2% plus fusidic acid 0.03% cream
  • Use oral antibiotics for superinfection.
    • Amoxicillin or clavulanic tablets
    • Cefalexin tablets
    • Clindamycin capsules
  • Use analgesic drugs (nonsteroidal anti-inflammatory drugs) orally.

Nursing Implications:

The use of cetuximab in treating colorectal and head and neck cancer has significantly affected patient outcomes. A strategic approach to managing skin toxicities that includes consensus recommendations from experts will guide clinicians in minimizing the incidence of skin rash, improve compliance, and optimize patient outcomes.

Nurses who will be managing grade 1 and 2 skin toxicities should receive education. In addition, use of a multidisciplinary approach when managing skin rashes is paramount. Facilities may choose to create algorithms as an effective strategy to establish consistent processes for the assessment and management of skin toxicities induced by EGFR-I therapy.