title: Randomized, open-label trial evaluating the preventive effect of tetracycline on afatinib induced-skin toxicities in non-small cell lung cancer patients.
abstract: BACKGROUND
  Afatinib has shown long progression free survival and improvement in quality of life in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Although afatinib causes acneiform rash, it can be manageable. Tetracyclines are usually used to treat it; nonetheless, there is no trial that evaluates their prophylactic efficacy on afatinib induced-skin toxicities (AIST).
  
  
  METHODS
  This open-label, randomized, controlled trial assessed the preventive effect of tetracycline for reducing afatinib-skin toxicities in NSCLC patients receiving afatinib 40 mg/day. Patients were randomly assigned to receive pre-emptive treatment with tetracycline 250 mg every 12h for 4 weeks or not. Reactive treatment in both groups included general dermatological recommendations such as use of skin moisturizers, sunscreen and topical steroids, according to toxicity severity. All patients were blindly monitored for skin toxicities by an expert dermatologist at the start of treatment with afatinib (day 0), weeks 2 and 4 of treatment. The protocol is registered on clinicaltrials.gov (NCT01880515).
  
  
  RESULTS
  We included 90 patients, no differences were found in clinical and dermatological baseline characteristics. Rash incidence of any grade, and grade ≥2 was less frequent in the pre-emptive arm vs. the control arm (44.5 vs. 75.6%, RR 0.4 [95% CI 0.17-0.99], p=0.046 and 15.6 vs. 35.6%, RR 0.35 [95% CI, 0.12-0.91], p=0.030, respectively). No difference was found in paronychia, xerosis, mucositis, folliculitis, and skin fissure. No adverse event was associated with tetracycline. Neither rash nor pre-emptive tetracycline impacted on response rate, progression-free or overall survivals.
  
  
  CONCLUSIONS
  Pre-emptive tetracycline was well tolerated and reduced the rash incidence and severity associated with afatinib in more than 60%.
authors.affiliation: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico; Experimental Oncology Laboratory, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico; Medicine School of Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico. Electronic address: ogar@servidor.unam.mx.
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
authors.affiliation: Dermatological Clinic, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Vega-González
authors.affiliation: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
authors.forename: Diego
authors.initials: D
authors.lastname: López-Macías
authors.affiliation: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
authors.forename: Jorge Negueb
authors.initials: JN
authors.lastname: Martínez-Hernández
authors.affiliation: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
authors.forename: Ludwing
authors.initials: L
authors.lastname: Bacon-Fonseca
authors.affiliation: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
authors.forename: Eleazar Omar
authors.initials: EO
authors.lastname: Macedo-Pérez
authors.affiliation: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
authors.forename: Laura Alejandra
authors.initials: LA
authors.lastname: Ramírez-Tirado
authors.affiliation: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
authors.forename: Diana
authors.initials: D
authors.lastname: Flores-Estrada
authors.affiliation: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: de la Garza-Salazar
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D065129:Pre-Exposure Prophylaxis; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D012871:Skin Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control*; D013752:Tetracycline / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077716:Afatinib; D013752:Tetracycline
keywords: Afatinib; Non-small cell lung cancer; Skin toxicities; Tetracycline; Tirosine kinase inhibitors; Toxicity severity