Gemcitabine induced skin rash

Abstract

Gemcitabine is used in various carcinomas like lung cancer, pancreatic cancer, bladder cancer and breast cancer in adults. It is considered to be a well-tolerated drug with little known side effects [1]. The reported toxic effects of gemcitabine include myelosuppression, altered liver function tests, flu-like syndrome, bronchospasm, rash, itching, and fever [2]. Skin reactions are rarely reported [1-4], the reported incidence being 7%-30% [4].

Topical application of gemcitabine generates microvesicle particles in human and murine skin

“…[26][27][28] Of significance, multiple studies have reported the abilities of PAFR antagonists to control the growth of cancer cells or augment the responses of therapeutic agents. 26,29,30 Given that gemcitabine chemotherapy used against multiple human malignancies either alone or in combination with other agents, exhibits adverse effects, including skin rash/necrosis, [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] our current studies sought to determine the potential role of MVP release in the pathologic effects of topical gemcitabine application. To that end, pharmacologic approaches using human skin explants and genetic approaches using murine skin were used as relevant models.…”

“…MVPs were resuspended in filtered PBS and the concentration was determined via nanosight tracking analysis (NTA) using the NanoSight NS300 instrument (NanoSight Ltd, Malvern Instruments, Malvern, UK) as per our published reports 29–31 . The baseline MVP release from human and murine skin by vehicle (control) treatment ranges from 10 8 to 10 9 …”

“…In particular, topical use of chemotherapy has also been employed in the treatment of skin conditions such as non‐melanoma skin cancer, actinic keratoses, and skin aging 4,5 . However, often these drugs are associated with adverse side effects, including localized skin eruptions and necrosis as well as systemic pathologies, including ototoxicity and neutropenia 6–11 . Gemcitabine is one of the commonly used chemotherapy drugs, which has been used either alone, or in combination with other antineoplastic agents for the treatment of malignancies, including pancreatic cancer, non‐small cell lung cancer, intrahepatic cholangiocarcinoma, colorectal cancer, ovarian cancer, breast cancer, and melanoma 12–18 .…”

“…29,30 Notably, MVPs are small nano-sized cellular bodies of $100-1000 nm diameter that are released from a wide variety of cell types via exocytosis in response to various stimuli, including anticancer agents, and serve to mediate cell-to-cell communications, both in physiological and pathological conditions. [29][30][31] Given that gemcitabine is a potential drug of clinical interest, yet associated with adverse events such as skin rash/necrosis, 9,10 and that it can be absorbed through the skin via processes, including passive diffusion, 32 we sought to determine if topical treatment of gemcitabine would stimulate MVP release containing PAF agonists, and define the associated mechanisms.…”

“… 4 , 5 However, often these drugs are associated with adverse side effects, including localized skin eruptions and necrosis as well as systemic pathologies, including ototoxicity and neutropenia. 6 , 7 , 8 , 9 , 10 , 11 Gemcitabine is one of the commonly used chemotherapy drugs, which has been used either alone, or in combination with other antineoplastic agents for the treatment of malignancies, including pancreatic cancer, non‐small cell lung cancer, intrahepatic cholangiocarcinoma, colorectal cancer, ovarian cancer, breast cancer, and melanoma. 12 , 13 , 14 , 15 , 16 , 17 , 18 Nevertheless, the development of tumor resistance mechanisms to gemcitabine therapy remained one of the ongoing challenges in its limited therapeutic efficacy.…”