title: Erlotinib augmentation with dapsone for rash mitigation and increased anti-cancer effectiveness.
abstract: BACKGROUND
  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. 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Thus, 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.
authors.affiliation: IIAIGC Study Center, 22 Church Street, Burlington, VT 05401 USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Kast
keywords: Dapsone; Erlotinib; Glioblastoma; Interleukin-8; Neutrophils; Non-small cell lung cancer; Ovarian cancer; Pancreas cancer; Quality of life; Rash