Clinical impact of minocycline on afatinib-related rash in patients with non-small cell lung cancer harboring epidermal growth factor receptor mutations

Respir Investig. 2018 Mar;56(2):179-183. doi: 10.1016/j.resinv.2017.11.009. Epub 2017 Dec 21.

Abstract

Background: The management of skin toxicity is crucial for efficient afatinib treatment, but the role of tetracycline class antibiotics (TCs) in managing these rashes is relatively unknown.

Methods: We reviewed the clinical records of patients who were administered afatinib for the treatment of non-small cell lung cancer harboring epidermal growth factor receptor mutations between October 2014 and November 2016. Twenty-five patients, who received TCs for the management of afatinib-related skin disorders, were enrolled.

Results: Minocycline was administered orally to participants. Afatinib-related toxic effects, such as rash, diarrhea, and paronychia, were observed in 92%, 92%, and 40% of cases, respectively. Although 24% of diarrhea and 4% of paronychia cases were rated grade 3 or higher, no severe cases of rash were observed during afatinib treatment. Of the 18 afatinib dose reductions, 14 (78%), three (17%), and one (6%) resulted from diarrhea, paronychia, and stomatitis, respectively; no patients required a dose reduction because of rash. When minocycline treatment started, 21 patients (84%) had a rash of grade 1 or less, and three patients had a grade 2 rash. A response to afatinib was observed in 18 patients (72%) and the median duration of afatinib administration was 501 days. An adverse event related to minocycline (grade 1 nausea) was observed in one patient.

Conclusions: A large proportion of the study patients started minocycline before grade 2 rash development and the severity of afatinib-related rash was lower than that previously reported. Oral TCs may be beneficial, especially if started early.

Keywords: Afatinib; Epidermal growth factor inhibitor; Minocycline; Rash; Tetracycline.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Diarrhea / chemically induced
  • Diarrhea / drug therapy
  • Epidermal Growth Factor / genetics*
  • Exanthema / chemically induced*
  • Exanthema / drug therapy*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Minocycline / administration & dosage*
  • Mutation*
  • Paronychia / chemically induced
  • Paronychia / drug therapy
  • Pyridines / adverse effects*
  • Pyridines / therapeutic use
  • Severity of Illness Index
  • Thiazoles / adverse effects*
  • Thiazoles / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Pyridines
  • Thiazoles
  • fatostatin
  • Epidermal Growth Factor
  • Minocycline