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

Dermatology Service and Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10022, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 01/2008; 25(34):5390-6. DOI: 10.1200/JCO.2007.12.6987
Source: PubMed


To evaluate the ability of either oral minocycline, topical tazarotene or both, to reduce or prevent cetuximab-related acneiform rash when administered starting on day 1 of cetuximab therapy.
Metastatic colorectal cancer patients preparing to initiate cetuximab were randomly assigned to receive daily oral minocycline or placebo, and to receive topical tazarotene application to either left or right side of the face. Both therapies were administered for 8 weeks.
Forty-eight eligible patients were randomly assigned to minocycline (n = 24) or placebo (n = 24). Total facial lesion counts were significantly lower in patients receiving minocycline at weeks 1 through 4. At week 4, a lower proportion of patients in the minocycline arm reported moderate to severe itch than in the placebo arm (20% v 50%, P = .05). Facial photographs, obtained at week 4, were reviewed for rash global severity. Patients in the minocycline arm trended toward lower frequency of moderate to severe rash than patients receiving placebo (20% v 42%, P = .13). The differences in total facial lesion counts and subjectively assessed itch were diminished by week 8. Cetuximab treatment was interrupted because of grade 3 skin rash in four patients in the placebo arm, and none in the minocycline arm. There was no observed clinical benefit to tazarotene application. Tazarotene treatment was associated with significant irritation, causing its discontinuation in one third of patients.
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.

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    • "Since treatment with target therapies is expensive, the development of severe skin toxicities can increase the costs of management. Therefore, less expensive, preemptive strategies to diminish skin toxicities are necessary and may be beneficial for patients [29] [30]. Moreover, with the advent of newer drugs in oncology, such as anti-EGFR therapies, newer toxicities that impair quality of life develop; pre-emptive treatments may help in treating this type of toxicities. "
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    ABSTRACT: Background Afatinib has shown long progression free survival and improvement in quality of life in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Although afatinib causes acneiform rash, it can be manageable. Tetracyclines are usually used to treat it; nonetheless, there is no trial that evaluates their prophylactic efficacy on afatinib induced-skin toxicities (AIST). Patients and methods This open-label, randomized, controlled trial assessed the preventive effect of tetracycline for reducing afatinib-skin toxicities in NSCLC patients receiving afatinib 40 mg/day. Patients were randomly assigned to receive pre-emptive treatment with tetracycline 250 mg every 12 hours for 4 weeks or not. Reactive treatment in both groups included general dermatological recommendations sucha as use of skin moisturizers, sunscreen and topical steroids, according to toxicity severity. All patients were blindly monitored for skin toxicities by an expert dermatologist at the start of treatment with afatinib (day 0), week 2 and week 4 of treatment. The protocol is registered on (NCT01880515). Results We included 90 patients, no differences were found in clinical and dermatological baseline characteristics. Rash incidence of any grade, and grade ≥2 was less frequent in the pre-emptive arm versus the control arm (55.6 vs. 75.6%, (RR) 0.4 [95% CI 0.17-0.99], p = 0.046 and 15.6 vs. 35.6%, RR 0.35 [95%CI, 0.12-0.91], p = 0.030; respectively). No difference was found in paronychia, xerosis, mucositis, folliculitis, and skin fissure. No adverse event was associated with tetracycline. Neither rash nor pre-emptive tetracycline impacted on response rate, progression-free or overall survivals. Conclusion Pre-emptive tetracycline was well tolerated and reduced the rash incidence and severity associated with afatinib in more than 60%.
    Lung Cancer 03/2015; · 3.96 Impact Factor
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    • "The group of patients who received minocycline showed benefit initially, during weeks 1 to 4, with less development of facial lesions and lower itch severity. After the 1st month this advantage was no longer evident [35]. Another randomized control trial by Jatoi et al. compared the efficacy of prophylactic oral tetracycline versus placebo on the incidence and severity of rash from EGFRIs. "
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    ABSTRACT: Epidermal growth factor inhibitors (EGFRI), the first targeted cancer therapy, are currently an essential treatment for many advance-stage epithelial cancers. These agents have the superior ability to target cancers cells and better safety profile compared to conventional chemotherapies. However, cutaneous adverse events are common due to the interference of epidermal growth factor receptor (EGFR) signaling in the skin. Cutaneous toxicities lead to poor compliance, drug cessation, and psychosocial discomfort. This paper summarizes the current knowledge concerning the presentation and management of skin toxicity from EGFRI. The common dermatologic adverse events are papulopustules and xerosis. Less common findings are paronychia, regulatory abnormalities of hair growth, maculopapular rash, mucositis, and postinflammatory hyperpigmentation. Radiation enhances EGFRI rash due to synergistic toxicity. There is a positive correlation between the occurrence and severity of cutaneous adverse effects and tumor response. To date, prophylactic systemic tetracycline and tetracycline class antibiotics have proven to be the most effective treatment regime.
    Dermatology Research and Practice 03/2014; 2014:734249. DOI:10.1155/2014/734249
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    • "At present, minocycline hydrochloride (minocycline) with steroidal agents are recognized as supportive treatment for the prevention of skin disorder with anti-EGFR antibody, utilized in various institutes, in accordance with the results of the skin toxicity evaluation protocol with panitumumab (STEPP) study [13]. "
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    ABSTRACT: Panitumumab is a full human epidermal growth factor receptor (EGFR) monoclonal antibody, an agent for metastatic colorectal cancer therapy. One of the most general adverse events of anti-EGFR monoclonal antibody therapy is skin disorder. At the present time, although prophylaxis of skin disorder is important for continuation of cancer therapy, there are no effective precautionary treatments. A 73-year-old male with sigmoid colon cancer and synchronous lung metastasis was treated with panitumumab, an alone anti-EGFR monoclonal antibody as the third-line therapy.During the nine courses of the therapy, the response was stable disease (SD), but skin disorder gradually appeared obviously (CTCAE version 4.0: Grade 2). After 1 month of administration of AboundTM, symptoms of the skin disorder improved (CTCAE version 4.0: Grade 1), thus the antibody therapy could be continued. We report that AboudTM was apparently effective in the treatment for anti-EGFR antibody-associated skin disorder. In the future, AboundTM could be expected as an agent for skin disorder as one of the side effects of colorectal cancer therapy.
    World Journal of Surgical Oncology 02/2014; 12(1):35. DOI:10.1186/1477-7819-12-35 · 1.41 Impact Factor
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