Prophylactic Topical Treatment for EGFR Inhibitor-Induced Papulopustular Rash: A Randomized Clinical Trial

Abstract

<b><i>Background:</i></b> The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60–85%. <b><i>Objective:</i></b> To investigate prophylactic topical treatment for EGFRI-induced rash. <b><i>Methods:</i></b> A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions. <b><i>Results:</i></b> The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (<i>p</i> = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (<i>p</i> = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA. <b><i>Conclusions:</i></b> Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

“…Due to the important role of EGFR in the normal physiological function of the skin, the incidence of adverse skin reactions caused by EGFR inhibitors is 60%-85%. These adverse reactions often lead to the reduction or even withdrawal of antitumor drugs ( 175 ). Therefore, preventing skin toxicity is increasingly gaining attention by investigators.…”

“…In addition to the aforementioned studies on the preventive use of antibiotics, nonsteroidal anti-inflammatory drugs may also play a role in preventing EGFR inhibitor-related rashes ( 186 ). Local prophylactic use of 3% chloramphenicol + 0.5% prednisolone ointment significantly reduced the severity of facial papulopustular exanthemas induced by EGFR inhibitors ( 175 ). Although studies have shown that preventive use of vitamin K3 cream does not reduce the number of papulopustular exanthemas ( 187 ), preventive use of vitamin K1 cream can reduce the incidence of grade 2 or higher rashes ( 188 ).…”

Prevention and management of acneiform rash associated with EGFR inhibitor therapy: A systematic review and meta‐analysis

“…There were 26 articles (1926 patients) included in this systematic review: 12 assessed oral antibiotics, [14][15][16][19][20][21][24][25][26][27][28]35 three assessed topical antibiotics, 30,36,37 four assessed vitamin K topical 22,29,31,38 two studies assessed topical EGFR ointment, 33,39 and there was one study for each of the following treatments; topical spironolactone, 34 topical pimecrolimus, 17 proprietary skin spray (Evozac Calming Skin Spray), 23 sunscreen, 18 and topical adapalene. 32 Among the studies assessing oral antibiotics, five assessed minocycline, 15,25,26,28,35 three assessed tetracycline, 16,20,24 three assessed doxycycline, 19,27 and one assessed lymecycline.…”

“…The risk of bias in each study was assessed using the risk of bias tool described in the Cochrane handbook 42 (Figure 2). Of the 26 studies included, there were 16 RCTs, [14][15][16][18][19][20]23,29,[31][32][33][34][36][37][38][39] nine prospec- tive open-label studies, 17,21,22,24,25,27,28,30,35 and one retrospective study. 26 Of the RCTs assessed, eight did not adequately describe how patients were randomized 14,15,19,23,32,34,37,38 and four of these studies did not seem to have both patients and personnel blinded; 14,19,37,38 thus, leading to potential selection and performance bias in some studies.…”

“…Of the 26 studies included, there were 16 RCTs, [14][15][16][18][19][20]23,29,[31][32][33][34][36][37][38][39] nine prospec- tive open-label studies, 17,21,22,24,25,27,28,30,35 and one retrospective study. 26 Of the RCTs assessed, eight did not adequately describe how patients were randomized 14,15,19,23,32,34,37,38 and four of these studies did not seem to have both patients and personnel blinded; 14,19,37,38 thus, leading to potential selection and performance bias in some studies. The rest of the included RCTs were double-blinded in a suitable manner using either identical placebo tablets or identical appearing topical products.…”