Skip to main content
Top
Published in: American Journal of Clinical Dermatology 3/2015

01-06-2015 | Original Research Article

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

Authors: Akira Shinohara, Masafumi Ikeda, Hiroyuki Okuyama, Misaki Kobayashi, Hideki Funazaki, Shuichi Mitsunaga, Satoshi Shimizu, Izumi Ohno, Hideaki Takahashi, Yasuhiko Ichida, Kunio Takahashi, Takuji Okusaka, Shinichiro Saitoh

Published in: American Journal of Clinical Dermatology | Issue 3/2015

Login to get access

Abstract

Background

Erlotinib has been reported as being associated with a high incidence of skin toxicities such as acneiform rash, paronychia, and xerosis.

Objective

The aim of this study was to evaluate the efficacy of prophylactic minocycline treatment for the skin toxicities induced by erlotinib as compared with deferred minocycline treatment in patients with pancreatic cancer treated with erlotinib plus gemcitabine.

Methods

A total of 96 patients were studied retrospectively, of whom 44 received prophylactic minocycline between August 2012 and June 2013 and 52 received deferred minocycline treatment between August 2011 and July 2012 at the National Cancer Center Hospital East, Kashiwa, Japan. In the prophylactic minocycline group, 200 mg/day oral minocycline was prophylactically administered during the treatment period.

Results

The incidence rate of acneiform rash and xerosis of any grade during the first 6 weeks of treatment was significantly reduced in the prophylactic minocycline group compared with the deferred minocycline treatment group (47.7 vs. 80.8 %, p < 0.001; 2.3 vs. 19.2 %, p = 0.01). Multivariate analysis identified prophylactic minocycline as a significant independent factor associated with the incidence of acneiform rash and xerosis of any severity (odds ratio [OR] 0.16, 95 % confidence interval [CI] 0.06–0.46, p < 0.001; OR 0.11, 95 % CI 0.01–0.90, p = 0.04).

Conclusion

Prophylactic minocycline appears to be useful for the management of erlotinib-related acneiform rash and xerosis during chemotherapy in patients with advanced pancreatic cancer.
Literature
1.
go back to reference Moore MJ, Goldstein D, Hamm J, Figer A, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the national cancer institute of canada clinical trial group. J Clin Oncol. 2007;25:1960–6.PubMed Moore MJ, Goldstein D, Hamm J, Figer A, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the national cancer institute of canada clinical trial group. J Clin Oncol. 2007;25:1960–6.PubMed
2.
go back to reference Okusaka T, Furuse J, Funakoshi A, et al. Phase II study of erlotinib plus gemcitabine in Japanese patients with unresectable pancreatic cancer. Cancer Sci. 2011;102:425–31.PubMed Okusaka T, Furuse J, Funakoshi A, et al. Phase II study of erlotinib plus gemcitabine in Japanese patients with unresectable pancreatic cancer. Cancer Sci. 2011;102:425–31.PubMed
3.
go back to reference Nakagawa K, Kudoh S, Ohe Y, et al. Postmarketing surveillance study of erlotinib in Japanese patients with non-small-cell lung cancer (NSCLC): an interim analysis of 3488 patients (POLARSTAR). J Thorac Oncol. 2012;7:1296–303.PubMed Nakagawa K, Kudoh S, Ohe Y, et al. Postmarketing surveillance study of erlotinib in Japanese patients with non-small-cell lung cancer (NSCLC): an interim analysis of 3488 patients (POLARSTAR). J Thorac Oncol. 2012;7:1296–303.PubMed
4.
go back to reference Galimont-Collen AF, Vos LE, Lavrijsen AP, et al. Classification and management of skin, hair, nail and mucosal side-effects of epidermal growth factor receptor (EGFR) inhibitors. Eur J Cancer. 2007;43:845–51.PubMed Galimont-Collen AF, Vos LE, Lavrijsen AP, et al. Classification and management of skin, hair, nail and mucosal side-effects of epidermal growth factor receptor (EGFR) inhibitors. Eur J Cancer. 2007;43:845–51.PubMed
5.
go back to reference Scope A, Agero AL, Dusza SW, et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol. 2007;25:5390–6.PubMed Scope A, Agero AL, Dusza SW, et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol. 2007;25:5390–6.PubMed
6.
go back to reference Lacouture ME, Michell EP, Piperdi B, et al. Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28:1351–7.PubMed Lacouture ME, Michell EP, Piperdi B, et al. Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28:1351–7.PubMed
7.
go back to reference Wacker B, Nagrani T, Weinberg J, et al. Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies. Clin Cancer Res. 2007;13:3913–21.PubMed Wacker B, Nagrani T, Weinberg J, et al. Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies. Clin Cancer Res. 2007;13:3913–21.PubMed
8.
go back to reference Wheatley-Price P, Ding K, Seymour L, et al. Erlotinib for advanced non-small-cell lung cancer in the elderly: an analysis of the National Cancer Institute of Canada Clinical Trials Group study BR.21. J Clin Oncol. 2008;26:2350–7.PubMed Wheatley-Price P, Ding K, Seymour L, et al. Erlotinib for advanced non-small-cell lung cancer in the elderly: an analysis of the National Cancer Institute of Canada Clinical Trials Group study BR.21. J Clin Oncol. 2008;26:2350–7.PubMed
9.
go back to reference Jatoi A, Green EM, Rowland KM, et al. Clinical predictors of severe cetuximab-induced rash: observation from 933 patients enrolled in North Central Cancer Treatment Group study N0147. Oncology. 2009;77:120–3.CrossRefPubMedCentralPubMed Jatoi A, Green EM, Rowland KM, et al. Clinical predictors of severe cetuximab-induced rash: observation from 933 patients enrolled in North Central Cancer Treatment Group study N0147. Oncology. 2009;77:120–3.CrossRefPubMedCentralPubMed
10.
go back to reference Perez-Soler R, Chachoua A, Hammond LA, et al. Determinations of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol. 2004;22:3238–47.PubMed Perez-Soler R, Chachoua A, Hammond LA, et al. Determinations of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol. 2004;22:3238–47.PubMed
11.
go back to reference Soulieres D, Senzer NN, Vokes EE, et al. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. J Clin Oncol. 2004;22:3238–47. Soulieres D, Senzer NN, Vokes EE, et al. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. J Clin Oncol. 2004;22:3238–47.
12.
go back to reference Nanney LB, Stoscheck CM, King LE Jr, et al. Immunolocalization of epidermal growth factor receptors in normal developing human skin. J Invest Dermatol. 1990;94:742–8.PubMed Nanney LB, Stoscheck CM, King LE Jr, et al. Immunolocalization of epidermal growth factor receptors in normal developing human skin. J Invest Dermatol. 1990;94:742–8.PubMed
13.
go back to reference Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. Targ Oncol. 2009;4:107–19. Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. Targ Oncol. 2009;4:107–19.
14.
go back to reference Pastore S, Mascia F, Mariotti F, et al. ERK1/2 regulates epidermal chemokine expression and skin inflammation. J Immunol. 2005;174:5047–56.PubMed Pastore S, Mascia F, Mariotti F, et al. ERK1/2 regulates epidermal chemokine expression and skin inflammation. J Immunol. 2005;174:5047–56.PubMed
15.
go back to reference Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006;6:803–12.PubMed Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006;6:803–12.PubMed
16.
go back to reference Pruzanski W, Greenwald RA, Street IP, et al. Inhibition of enzymatic activity of phospholipases A2 by minocycline and doxycycline. Biochem Pharmacol. 1992;44:1165–70.PubMed Pruzanski W, Greenwald RA, Street IP, et al. Inhibition of enzymatic activity of phospholipases A2 by minocycline and doxycycline. Biochem Pharmacol. 1992;44:1165–70.PubMed
17.
go back to reference Amin AR, Attur MG, Thakker GD, et al. A novel mechanism of action of tetracyclines: effects on nitric oxide synthases. Proc Natl Acad Sci. 1996;93:14014–9.PubMedCentralPubMed Amin AR, Attur MG, Thakker GD, et al. A novel mechanism of action of tetracyclines: effects on nitric oxide synthases. Proc Natl Acad Sci. 1996;93:14014–9.PubMedCentralPubMed
18.
go back to reference Dreno B, Bettoli V, Ochsendorf F, et al. European recommendations on the use of oral antibiotics for acne. Eur J Dermatol. 2004;14:391–9.PubMed Dreno B, Bettoli V, Ochsendorf F, et al. European recommendations on the use of oral antibiotics for acne. Eur J Dermatol. 2004;14:391–9.PubMed
19.
go back to reference Vincent JA, Mohr S. Inhibition of caspase-1/interleukin-1beta signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes. 2007;56:224–30.CrossRefPubMed Vincent JA, Mohr S. Inhibition of caspase-1/interleukin-1beta signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes. 2007;56:224–30.CrossRefPubMed
20.
go back to reference Shu KY, Kindler HL, Medenica M, et al. Doxycycline for the treatment of paronychia induced by the epidermal growth factor receptor inhibitor cetuximab. Br J Dermatol. 2006;154:191–2.PubMed Shu KY, Kindler HL, Medenica M, et al. Doxycycline for the treatment of paronychia induced by the epidermal growth factor receptor inhibitor cetuximab. Br J Dermatol. 2006;154:191–2.PubMed
21.
go back to reference Stintzing S, Kapaun C, Laubender RP, et al. Prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer patients and its correlation with parameters of the epidermal growth factor receptor signal transduction pathway: results from a randomized trial of the GERMAN AIO CRC Study Group. Int J Cancer. 2013;132:236–45.PubMed Stintzing S, Kapaun C, Laubender RP, et al. Prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer patients and its correlation with parameters of the epidermal growth factor receptor signal transduction pathway: results from a randomized trial of the GERMAN AIO CRC Study Group. Int J Cancer. 2013;132:236–45.PubMed
22.
go back to reference Migliaccio A, Castoria G, Di Domenico M, et al. Steroid-induced androgen receptor-oestradiol receptor-Src complex triggers prostate cancer cell proliferation. EMBO J. 2000;19:5406–17.PubMedCentralPubMed Migliaccio A, Castoria G, Di Domenico M, et al. Steroid-induced androgen receptor-oestradiol receptor-Src complex triggers prostate cancer cell proliferation. EMBO J. 2000;19:5406–17.PubMedCentralPubMed
23.
go back to reference Migliaccio A, Castoria G, Di Domenico M, et al. Crosstalk between EGFR and extranuclear steroid receptors. Ann NY Acad Sci. 2006;1089:194–200.PubMed Migliaccio A, Castoria G, Di Domenico M, et al. Crosstalk between EGFR and extranuclear steroid receptors. Ann NY Acad Sci. 2006;1089:194–200.PubMed
Metadata
Title
Efficacy of Prophylactic Minocycline Treatment for Skin Toxicities Induced by Erlotinib Plus Gemcitabine in Patients with Advanced Pancreatic Cancer: A Retrospective Study
Authors
Akira Shinohara
Masafumi Ikeda
Hiroyuki Okuyama
Misaki Kobayashi
Hideki Funazaki
Shuichi Mitsunaga
Satoshi Shimizu
Izumi Ohno
Hideaki Takahashi
Yasuhiko Ichida
Kunio Takahashi
Takuji Okusaka
Shinichiro Saitoh
Publication date
01-06-2015
Publisher
Springer International Publishing
Published in
American Journal of Clinical Dermatology / Issue 3/2015
Print ISSN: 1175-0561
Electronic ISSN: 1179-1888
DOI
https://doi.org/10.1007/s40257-015-0116-x

Other articles of this Issue 3/2015

American Journal of Clinical Dermatology 3/2015 Go to the issue