Efficacy of Prophylactic Minocycline Treatment for Skin Toxicities Induced by Erlotinib Plus Gemcitabine in Patients with Advanced Pancreatic Cancer: A Retrospective Study

Shinohara, Atsushi; Ikeda, Masafumi; Okuyama, Hiroomi; Kobayashi, Misaki; Funazaki, Hideki; Mitsunaga, Shuichi; Shimizu, Satoshi; Ohno, Izumi; Takahashi, Hideaki; Ichida, Yasuhiko; Takahashi, Kunio; Okusaka, Takuji; Saitoh, S

doi:10.1007/s40257-015-0116-x

Cited by 15 publications

(18 citation statements)

References 21 publications

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“…Since the incidence of skin disorders is high, and the quality of life (QOL) of patients is decreased, immediate elucidation of the pathogenesis of skin disorders and treatment based on the principle of direct approach to the skin is needed. In the last 5 years or so, supportive treatment regimens with TKIs have incorporated oral administration of minocycline for the purpose of preventing rashes [3][4][5][6]. However, this method of oral administration of minocycline is a provisional procedure similar to the treatment of acne rash in adolescents, and there is no clear evidence that oral administration of minocycline has any effect on EGFR-TKI-induced eruptions.…”

Section: Introductionmentioning

confidence: 99%

Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer

2020

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Background: While epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) exert a breakthrough effect, the incidence of skin disorders as a side effect has significantly reduced patients' quality of life. This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Giotrif®), a secondgeneration EGFR-TKI, and established a skin disorder mouse model to investigate the protective effect of minocycline.Methods: First, under inhalation anesthesia with isoflurane, the back of a male ddy mouse was shaved, and afatinib petrolatum was applied alone or in combination with minocycline to observe the state of the skin and measure transepidermal water transpiration (TEWL). Next, afatinib was administered orally to mice, and minocycline petrolatum was applied to observe whether the skin disorder was prevented and its effect on repair of the skin disorder.Results: Skin injury occurred on the back of the mouse following afatinib (1 mg/g in petrolatum) application, and scab formation was observed. Application of minocycline prevented and improved the skin disorder caused by afatinib. When the minocycline-petrolatum mixture was applied to the mouse that developed the skin disorder, a significant improvement in TEWL was observed, and skin repair was observed macroscopically.Conclusions: These results suggest that minocycline petrolatum applied locally prevents and repairs afatinibinduced skin disorders of non-small cell lung cancer patients. Histological examination of skin has provided insights into the mechanism of the occurrence of afatinib-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.

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Section: Introductionmentioning

confidence: 99%

Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer

2020

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“…Since the incidence of skin disorders is high, and the quality of life (QOL) of patients is 3 decreased, immediate elucidation of the pathogenesis of skin disorders and treatment based on the principle of direct approach to the skin is needed. In the last five years or so, supportive treatment regimens with TKIs have incorporated oral administration of minocycline for the purpose of preventing rashes [3,4] [5] [6]. However, this method of oral administration of minocycline is a provisional procedure similar to the treatment of acne rash in adolescents, and there is no clear evidence that oral administration of minocycline has any effect on EGFR-TKIs-induced eruptions.…”

Section: Introductionmentioning

confidence: 99%

Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer

Sano

Nakadate

Hanada

2020

Preprint

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Background While epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs) exert a breakthrough effect, the incidence of skin disorders as a side effect has significantly reduced patients' quality of life. Objective This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Geotrif®), a second-generation EGFR-TKI, and established a skin disorder mouse model to investigate the protective effect of minocycline. Methods First, under inhalation anesthesia with isoflurane, the back of a male ddy mouse was shaved, and afatinib petrolatum was applied alone or in combination with minocycline to observe the state of the skin and measure transepidermal water transpiration (TEWL). Next, afatinib was administered orally to mice, and minocycline petrolatum was applied to observe whether the skin disorder was prevented and its effect on repair of the skin disorder. Results Skin injury occurred on the back of the mouse following afatinib (1 mg/g in petrolatum) application, and scab formation was observed. Application of minocycline prevented and improved the skin disorder caused by afatinib. When the minocycline-petrolatum mixture was applied to the mouse that developed the skin disorder, a significant improvement in TEWL was observed, and skin repair was observed macroscopically. Discussion These results suggest that minocycline applied both locally and orally prevents and repairs afatinib-induced skin disorders. Histological examination of skin elucidated the mechanism of the occurrence of the EGFR-TKI-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.

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“…15 It is now widely used in the management of dermatitis associated with targeted therapy in cancer 16,17 ; use of prophylactic oral minocycline significantly reduced grade !2 rash compared with use reactive topical steroids (44.0% vs 84.6%, P Z .04) 18 and reduced moderate or severe itching compared with placebo (20% vs 50%, P Z .05) 19 in colorectal patients, and its prophylactic use resulted in lower incidence of rash in pancreatic cancer compared with deferred treatment (47.7% vs 80.8%, P < .001). 20 Our preliminary studies and the published data by others showed that minocycline is safe with a positive trend toward reducing the adverse events after cancer treatment (feeding tube, fatigue, diarrhea, and neuropathy). 16,[21][22][23][24] Those studies were either single arm phase 2 or phase 3 with small sample size and unpowered to detect the effect size or to show statistically significant reduction in the treatment-related toxicities in cancer patients after minocycline.…”

Section: Introductionmentioning

confidence: 52%

Minocycline Reduces Chemoradiation-Related Symptom Burden in Patients with Non-Small Cell Lung Cancer: A Phase 2 Randomized Trial

Wang

Shi

Mendoza

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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Using a low toxic agent that potentially with anti-inflammatory proprieties, minocycline, we conducted Phase II randomized placebo controlled trial and observed positive effect of reducing fatigue and other symptoms in patients undergoing CRT for NSCLC.Purpose: In patients with non-small cell lung cancer (NSCLC), concurrent chemoradiation therapy (CRT) exacerbates a cluster of difficult-to-manage symptoms, especially cancer-related fatigue. Minocycline is a readily available, low-cost antibiotic with antiinflammatory properties. We conducted a phase 2 randomized, doubleblinded, placebo-controlled trial to investigate the effect of minocycline in reducing CRT-symptom burden in NSCLC. Methods and Materials: Patients with NSCLC scheduled to receive CRT provided consent and were randomized to receive either minocycline (100 mg twice daily) or a matching placebo during 6 to 7 weeks of CRT. Patient-reported fatigue and other symptoms were assessed on MD Anderson Symptom Inventory weekly from the start of CRT for 12 weeks. The primary outcome was 12-week (AE2 days) area under the curve for symptom burden, which was compared between treatment groups. Results: Forty of 49 enrolled patients (80%) were evaluable (19 on minocycline and 21 on placebo). There were no grade 3 þ adverse events related to the study medication. Fatigue was significantly reduced in the minocycline group compared with placebo group during the 12-week trial period (area under the curve Z 31.2 AE 14.2 vs 45.0 AE 20.9, P Z .011), with a large effect size (Cohen's d Z 0.77). Pain (Cohen's d Z 0.54) and shortness of breath (Cohen's d Z 0.55) were also significantly reduced in the minocycline group (all P < .05).

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Efficacy of Prophylactic Minocycline Treatment for Skin Toxicities Induced by Erlotinib Plus Gemcitabine in Patients with Advanced Pancreatic Cancer: A Retrospective Study

Abstract: Prophylactic minocycline appears to be useful for the management of erlotinib-related acneiform rash and xerosis during chemotherapy in patients with advanced pancreatic cancer.

Cited by 15 publications

References 21 publications

Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer

Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer

Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer

Minocycline Reduces Chemoradiation-Related Symptom Burden in Patients with Non-Small Cell Lung Cancer: A Phase 2 Randomized Trial

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