Erlotinib augmentation with dapsone for rash mitigation and increased anti-cancer effectiveness.

R E Kast

doi:10.1186/s40064-015-1441-5

Abstract

BackgroundThe epidermal growth factor receptor tyrosine kinase inhibitor erlotinib has failed in many ways to be as potent in the anti-cancer role as pre-clinical studies would have suggested. This paper traces some aspects of this failure to a compensatory erlotinib-mediated increase in interleukin-8. Many other-but not all- cancer chemotherapeutic cytotoxic drugs also provoke a compensatory increase in a malignant clone’s interleukin-8 synthesis. Untreated glioblastoma and other cancer cells themselves natively synthesize interleukin-8. Interleukin-8 has tumor growth promoting, mobility and metastasis formation enhancing, effects as well as pro-angiogenesis effects.FindingsThe old sulfone antibiotic dapsone- one of the very first antibiotics in clinical use- has demonstrated several interleukin-8 system inhibiting actions. Review of these indicates dapsone has potential to augment erlotinib effectiveness. Erlotinib typically gives a rash that has recently been proven to come about via an erlotinib triggered up-regulated keratinocyte interleukin-8 synthesis. The erlotinib rash shares histological features reminiscent of typical neutrophilic dermatoses. Dapsone has an established therapeutic role in current treatment of other neutrophilic dermatoses.ConclusionThus, dapsone has potential to both improve the quality of life in erlotinib treated patients by amelioration of rash as well as to short-circuit a growth-enhancing aspect of erlotinib when used in the anti-cancer role.

Highlights

The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib has failed in many ways to be as potent in the anti-cancer role as pre-clinical studies would have suggested
A little noted breakthrough in understanding glioblastoma pathophysiology came from a study showing that endothelial cells can upregulate their synthesis of IL-8 in response to glioblastoma cells’ secreted IL-8, and vice versa (Infanger et al 2013), findings that replicate the feedforward system of Schruefer et al (2005) between neutrophils and endothelial cells, findings that again support the potential role for dapsone in glioblastoma treatment
This paper reviewed the growth promoting aspects of IL-8 in a few selected cancers and data showing how erlotinib, a drug designed to- and in a limited way succeeded in decreasing cancer growth, can and often does increase IL-8 in skin

Summary

Introduction

The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib has failed in many ways to be as potent in the anti-cancer role as pre-clinical studies would have suggested. Conclusion: dapsone has potential to both improve the quality of life in erlotinib treated patients by amelioration of rash as well as to short-circuit a growth-enhancing aspect of erlotinib when used in the anti-cancer role.

Results

Conclusion