Scope, A., Agero, A.L., Dusza, S.W., Myskowski, P.L., Lieb, J.A., Saltz, L., . . . Halpern, A.C. (2007). Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. Journal of Clinical Oncology, 25, 5390–5396.

To compare the effectiveness of placebo versus minocycline 100 mg every day for eight weeks, beginning on day 1 of cetuximab infusion, to prevent or reduce cetuximab-induced rash in patients with metastatic colorectal cancer.

To compare the effectiveness of receiving tazarotene cream BID for eight weeks on one side of the patient’s face versus not receiving the topical treatment on the other side of the patient’s face.

Twenty-four patients were randomized to the oral minocycline (100 mg per day) arm, and 24 patients were randomized to the oral placebo arm. Treatment was administered starting on day 1 of cetuximab therapy and continued for eight weeks.

All patients received open-label, topical tazarotene 0.05% cream (Tazorac^®) application to one side of their face, starting on day 1 of cetuximab therapy and continuing for eight weeks.

• The study reported on a sample of 48 adult men and women with stage IV metastatic colorectal cancer, who were preparing to initiate treatment with cetuximab.
• Mean patient age was 61 years (range 39–83 years).

• Single center
• Memorial Sloan-Kettering Cancer Center

This was a randomized, double-blind, placebo-controlled trial.

Follow-up clinical assessment was completed at weeks 1, 2, 4, and 8, with questionnaires and skin examination, including skin lesion counts and digital photos.

• Initially, 48 patients were randomized in this study. At the end of the eight-week trial, 35 patients were included in the final analysis (18 patients in the minocycline arm and 17 patients in the placebo arm).
• A significant overall difference existed in log lesion counts between the minocycline arm (fewer lesions) and the placebo arm (p = 0.005). The difference was apparent by week 1, peaked at weeks 2 and 4, and tapered by the end of the study (week 8).
• At week 4, a decreased proportion of patients in the minocycline arm reported moderate-severe itch compared to those in the placebo arm.
• Patients in the minocycline arm trended toward decreased frequency of moderate-severe rash compared to those in the placebo arm. Those differences diminished by week 8.
• In four patients in the placebo arm (8%), cetuximab treatment was interrupted because of grade 3 dermatologic adverse events. Cetuximab treatment was not interrupted for any patients in the minocycline arm.
• Topical treatment with tazarotene did not translate into a meaningful clinical benefit.
• Of the 43 patients available for at least one clinical evaluation, 14 (33%) discontinued tazarotene prematurely as a result of local irritation.
• Three additional patients (7%) reported stopping tazarotene after one month because of subjective lack of efficacy compared to the control side of the face.
• In a review of facial photography at week 4 (n = 39), no difference existed in rash severity between the tazarotene and observation sides of the face (n = 34, 87%), and the rash was assessed as more severe in four patients (10%) who received tazarotene.

Prophylactic treatment with minocycline appears to significantly decrease the severity of acneform rash during the first eight weeks of cetuximab therapy. Continuation of this therapy beyond eight weeks is not beneficial.

Results suggest that topical tazarotene has no role in the management of cetuximab-induced rash.

• The sample size was small (48 at the start of the study; reduced to 35 by the end of eight weeks).
• The measurement tool or method used to grade rash symptoms was not described.
• A combination of interventions was used; therefore, determining the effectiveness of the individual interventions is difficult.