Abstract

ABSTRACT Background Panitumumab (Pmab) has been associated with a high incidence of skin toxicity. The STEPP study evaluated whether prophylactic treatment with a topical steroid and oral doxycycline during the first 6 weeks of Pmab-containing therapy reduced incidence of grade 2 or higher skin toxicities compared to reactive treatment. Prophylactic treatment resulted in skin toxicity incidence of 29% compared with 62% in the reactive treatment arm. Purpose The aim of this study was to evaluate the efficacy of combination prophylactic therapy with topical adapalene and oral minocycline in patients receiving Pmab. Methods Patients with KRAS wild-type unresectable/recurrent colorectal cancer enrolled in a prospective phase II clinical trial of third-line Pmab plus irinotecan (CPT-11) or Pmab monotherapy were included. Prophylactic therapy with topical adapalene, a third-generation topical retinoid used in the treatment of mild-to-moderate acne, and oral minocycline were started from one day prior to the first Pmab dose and continued for 6 weeks. Adapalene was administered once daily in the evening, along with oral minocycline 100 mg twice per day. Skin toxicity was evaluated according to NCI CTCAE, version 4. The primary endpoint was incidence of grade 2 or higher skin toxicities during the 6-week skin treatment period. Results Between January 2011 and December 2011, 48 patients were included in this study (27 men, 21 women; median age, 62.0 years; 43 CPT-11 + Pmab, 5 Pmab alone). During the 6 weeks of prophylactic therapy, incidence of skin toxicities (rash, dry skin, and paronychia) was 83.3%. The incidence of skin toxicities of grade 2 or higher was 29.2%, similar to STEPP trial results (29%). The median adherence to topical adapalene was 90% (range, 0-100%), while minocycline was 100% (range, 17-100%). In the good adapalene adherence group (≥median), the incidence of skin toxicity of grade 2 or higher was 20.8% compared to 37.5% in the poor adherence group ( Conclusion The incidence of skin toxicities during the 6 weeks of prophylactic therapy was similar to the STEPP trial. These results suggest that adapalene may be an effective prophylactic treatment option for management of Pmab-related skin toxicity. Disclosure All authors have declared no conflicts of interest.

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