Lacouture, M.E., Mitchell, E.P., Piperdi, B., Pillai, M.V., Shearer, H., Iannotti, N., . . . Yassine, M. (2010). Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. Journal of Clinical Oncology, 28, 1351–1357.

To examine the difference in incidence of specific grade 2 or higher skin toxicities of interest between patients with metastatic colorectal cancer in preemptive and reactive skin treatment groups during a six-week treatment period that included epidermal growth factor receptor inhibitors (EGFR-Is).

Eligible patients were randomly assigned to preemptive or reactive skin treatment arms. The chemotherapy regimen schedule was a random assignment stratification factor.

The preemptive skin treatment regimen was administered beginning on day –1 (one day before the administration of the first panitumumab dose) and continued through weeks 1 to 6.

Clinical and experimental data suggest that four major alterations occur in the skin of patients treated with EGFR-Is: follicular and interfollicular inflammation, bacterial superinfection, dry skin, and sensitivity to ultraviolet (UV) radiation. The rationale for selection of the preemptive skin regimen was based on those four alterations. The preemptive skin treatment regimen comprised the following.

• Skin moisturizer applied to the face, hands, feet, neck, back, and chest daily in the morning on rising (rationale: restore the permeability barrier and treat dry skin)
• Sunscreen (para-aminobenzoic acid [PABA] free, sun protection factor [SPF] ≥ 15, UVA and UVB protection) applied to exposed skin areas before going outdoors (rationale: prevent UV radiation–induced skin toxicity)
• topical corticosteroid (1% hydrocortisone cream) applied to face, hands, feet, neck, back, and chest at bedtime (rationale: instituted against cutaneous inflammation and pruritus)
• Semisynthetic tetracycline (doxycycline 100 mg BID) (rationale: anti-inflammatory and antibacterial properties)

The reactive skin treatment regimen comprised any treatments the investigator deemed necessary for the management of emergent skin toxicity and could be administered anytime during weeks 1 to 6. Patients randomly assigned to the reactive skin treatment group were not prohibited from using skin moisturizer or sunscreen at any time during the treatment if they chose to do so.

All patients were monitored weekly from weeks 1 to 7 for compliance with the randomized skin treatment regimen and for skin toxicity assessment.

• The study reported on a sample of 95 patients.
• The sample was 67% male and 33% female in the preemptive skin treatment group, and 55% male and 45% female in the reactive skin treatment group.

• Multi-site
• Outpatient
• United States

Patients were undergoing the active treatment phase of care.

This was a phase 2, multicenter, open-label, randomized clinical trial.

• Protocol-defined skin toxicities of interest included pruritus, acneform dermatitis, skin desquamation, exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.
• Dermatology Life Quality Index (DLQI): Assessed patient-reported quality of life (QOL) at screening, weeks 2 to 7, and the week 13 or 14 visit, depending on the skin treatment schedule. The DLQI comprises 10 simple questions to assess QOL in patients with skin disorders. The DLQI is scored on a scale from 0 to 30, where higher scores indicate more QOL impairment.
• Patient diary: Throughout the skin treatment period, patients completed a daily diary of symptoms and treatment compliance. The diary was shared with study personnel at each weekly clinic visit and was used for case report data entry.
   

• The incidence of protocol-specific grade 2 or higher skin toxicities during the six-week skin treatment period was 29% for the preemptive skin treatment group (23% grade 2 and 6% grade 3) and 62% for the reactive skin treatment group (40.4% grade 2 and 21.3% grade 3) (odds ratio, 0.3; 95% confidence interval [0.1, 0.6]).
• Acneform dermatitis at any grade occurred in 77% of patients in the preemptive skin treatment group and 85% in the reactive skin treatment group.
• Incidence of pruritus was similar in both groups.
• Seventeen percent of patients in the preemptive skin treatment group developed paronychia, compared to 36% in the reactive skin treatment group.

The preemptive skin treatment regimen was well tolerated. The incidence of specific grade 2 or higher skin toxicities during the six-week skin treatment period was lower in the preemptive skin treatment group compared with the reactive skin treatment group.

• The sample size was small (fewer than 100 patients enrolled).
• The only EGFR-I used to treat patients was panitumumab. Patients who were receiving cetuximab were not included in the study.
• The study was not blinded.
• Information was not provided on reactive treatments used for comparison of effectiveness or the stage at which reactive treatments were instituted.
• Patient compliance results were not reported.

The findings supported the importance of establishing a preemptive, comprehensive skin treatment regimen in patients treated with panitumumab to decrease skin toxicities and improve QOL. The skin toxicities are considered a class-based effect; therefore, these results may be generalized to other EGFR-Is.