Randomized Double-Blind Trial of Prophylactic Oral Minocycline and Topical Tazarotene for Cetuximab-Associated Acne-Like Eruption

Scope, Alon; Agero, Anna Liza C.; Dusza, Stephen W.; Myskowski, Patricia L.; Lieb, Jocelyn A.; Saltz, Leonard B.; Kemeny, Nancy E.; Halpern, Allan C.

doi:10.1200/jco.2007.12.6987

Cited by 253 publications

(195 citation statements)

References 33 publications

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“…Additionally, including various kinds of EGF-R inhibitors (erlotinib, cetuximab, panitumumab, gefitinib), several studies have examined the preventive effects of doxycycline (100mg) or minocycline (100mg) for 6-8 weeks, as well as topical hydrocortisone [20][21][22][23], some of which failed to show a statistically significant effect of tetracycline (500 mg twice a day for 4 weeks), as compared with placebo [20,21]. In a STEPP trial including patients receiving panitumumab with grade 2-3, doxycycline (100 mg twice a day) reduced the incidence of grade 2 to 3 toxicity as compared with placebo (29% versus 62%) at the endopoint of 6 weeks [23].…”

Section: Folliculitis (Acneiform Eruption)mentioning

confidence: 99%

Erlotinib-induced Adverse Skin Reactions

Yamamoto¹

2013

TOALLJ

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Abstract:Erlotinib is low molecular-weight quinazolin derivatives which selectively inhibit the epidermal growth factor receptor (EGF-R) tyrosine kinase activity of the intracellular domain, block autophosphorylation and the subsequent signaling cascades. EGF-R is expressed on basal keratinocytes, sebocytes, the outer root sheath of hairs, and endothelial cells in the skin, and plays important roles in the regulation of differentiation, proliferation, apoptosis, attachment and migration of keratinocytes, inflammation, and wound healing. Therefore, inhibition of EGF-R causes a number of cutaneous adverse reactions. Among them, severe skin lesions are very stressful, and impair quality of life of patients. Moreover, they even bring disadvantages such as drug withdrawal or interruption. Several review papers describe representative or common skin lesions which appear either during the first a few weeks or at later phases. Common skin manifestations include papular and pustular follicular eruptions (acneiform eruption), xerosis, paronychia, pruritus, and abnormalities of hairs; however, other than those eruptions, several unusual lesions are also induced. Early intervention of dermatologists and management of skin lesions are quite important, because discontinuance of the drug is unfavorable for patients with clinical benefits for cancers. In this brief review, various cutaneous manifestations seen in Japanese patients treated with erlotinib (Tarceva) are shown, and current management of representative severe conditions is also described.

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Section: Folliculitis (Acneiform Eruption)mentioning

confidence: 99%

Erlotinib-induced Adverse Skin Reactions

Yamamoto¹

2013

TOALLJ

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“…in most cases, prophylactic approaches were chosen. Prophylaxis with oral antibiotics (tetracycline or minocycline) alone was effective for the early phase of the exanthema during the first 4 weeks of anti-EGFR treatment (8,9). a decrease in the incidence of exanthemas of a grade greater than or equal to 2 in patients assigned to the tetracycline or minocycline group was noted.…”

Section: Discussionmentioning

confidence: 99%

Cetuximab-induced skin exanthema: Improvement by a reactive skin therapy

et al. 2010

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Abstract. More than 80% of patients treated with cetuximab develop an acneiform follicular skin exanthema. Grade 3 exanthema develops in 9-19% of these cases, bearing the risk of cetuximab dose-reduction or cessation. We retrospectively analysed a cohort of 20 patients treated with cetuximab and an in-house reactive skin protocol upon development of an exanthema. The reactive skin protocol was built up as follows: grade 1 exanthema: topical cleansing syndet (dermowas ® ) + topical metronidazole cream (rosiced ® ); grade 2 exanthema: grade 1 treatment + oral minocycline 50 mg twice per day; grade 3 exanthema: grade 2 treatment + topical corticoid (dermatop ® ) + topical nadifloxacin (Nadixa ® ). as soon as a grade 3 had improved to a grade less than or equal to 2, the application of the topical corticoid was ceased. during the initial 12 weeks of therapy with cetuximab, all patients developed a skin exanthema (20/20; 100%). of these, 2 patients (10%) developed a grade 3 exanthema, 10 patients (50%) experienced a grade 2 and 8 patients (40%) a grade 1 exanthema. Time to onset ranged from 1 to 4 weeks, with the average time to onset being 2.8 weeks. applying the reactive skin protocol after the first occurrence of an exanthema, the grade of exanthema was downgraded as follows: no patients (0%) had a persisting grade 3 exanthema, while only 2 patients (10%) experienced a persisting grade 2 exanthema and 8 patients (40%) a persisting grade 1 exanthema. in the majority of cases (10 patients; 50%), the reactive skin protocol completely controlled the exanthema (grade 0). The average time to exanthema reduction by one grade was 9.5 days. no dose reductions of cetuximab were necessary. cetuximab-induced skin exanthema is effectively managed by applying our reactive protocol. The simple protocol is based on a topical cleansing syndet and topical metronidazole and is to be intensified by the addition of oral minocycline, a topical corticoid and topical nadifloxacine, in cases of high-grade exanthema. More comprehensive results are expected from a prospective study with higher patient numbers that is currently being planned. Introductionepidermal growth factor receptor (eGFr) inhibitors are used as highly effective therapies for diverse tumour entities, including colorectal, head and neck, non-small cell lung and pancreatic cancers, among other malignancies (1-5). although eGFr inhibitors, such as cetuximab, are generally well tolerated and do not increase the classical adverse events of chemotherapy, they induce a skin exanthema that occurs in more than 80% of patients (1,4). While the exanthema has an acneiform appearance, its origin is nonetheless follicular (5). This follicular acneiform exanthema presents itself as maculae, papulae or small pustulae occurring on the face, décolleté or back, and may be accompanied by symptoms, such as burning or itching.Time to onset is between 2 and 3 weeks after the first application of the eGFr inhibitor. While the majority of patients develop only mild exanthemas (grades 1 or 2), 9-...

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“…Cetuximab and panitumumab do, however, increase incidences of some side effects (e.g., diarrhoea) from cytotoxic drugs. Nevertheless, integument-related toxicities are very common and may adversely affect patients' QoL if used on a long-term basis, although oral minocycline may be helpful in some patients (Scope et al, 2007). Furthermore, preemptive skin treatment (using skin moisturisers, sunscreen, topical steroid and oral doxycycline) starting before panitumumab-based treatment has recently been shown to reduce skin toxicity by 450% with improved QoL compared with reactive skin treatment, that is, starting treatment after development of skin rash (Lacouture et al, 2009).…”

Section: Treatment In Advanced Colorectal Cancer I Chau and D Cunninghammentioning

confidence: 99%

Treatment in advanced colorectal cancer: what, when and how?

Chau

Cunningham

2009

Br J Cancer

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Treatment of advanced colorectal cancer (CRC) increasingly requires a multidisciplinary approach and multiple treatment options add to the complexity of clinical decision-making. Recently novel targeted therapy against angiogenesis and epidermal growth factor receptor completed a plethora of phase III studies. The addition of bevacizumab to chemotherapy improved the efficacy over chemotherapy alone in both first and second line settings, although the magnitude of benefit may not be as great when a more optimal chemotherapy platform is used. Studies performed thus far did not address conclusively whether bevacizumab should be continued in subsequent lines of treatment. Anti-angiogenesis tyrosine kinase inhibitors have not shown any additional benefit over chemotherapy alone so far. Although some benefits were seen with cetuximab in all settings of treating advanced CRC, K-ras mutation status provides an important determinant of who would not benefit from such a treatment. Caution should be exercised in combining anti-angiogenesis with anti-EGFR strategy until further randomised data become available. In this review, we have focused on the implications of these trial results on the everyday management decisions of treating advanced CRC.

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Randomized Double-Blind Trial of Prophylactic Oral Minocycline and Topical Tazarotene for Cetuximab-Associated Acne-Like Eruption

Abstract: Prophylaxis with oral minocycline may be useful in decreasing the severity of the acneiform rash during the first month of cetuximab treatment. Topical tazarotene is not recommended for management of cetuximab-related rash.

Cited by 253 publications

References 33 publications

Erlotinib-induced Adverse Skin Reactions

Erlotinib-induced Adverse Skin Reactions

Cetuximab-induced skin exanthema: Improvement by a reactive skin therapy

Treatment in advanced colorectal cancer: what, when and how?

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