Nutritional Status, Body Surface, and Low Lean Body Mass/Body Mass Index Are Related to Dose Reduction and Severe Gastrointestinal Toxicity Induced by Afatinib in Patients With Non-Small Cell Lung Cancer

Oncologist. 2015 Aug;20(8):967-74. doi: 10.1634/theoncologist.2015-0058. Epub 2015 Jul 14.

Abstract

Background: The main reason for dose reduction of afatinib is gastrointestinal toxicity (GT). In a phase II study, we analyzed anthropometrical, nutritional, and biochemical factors associated with GT induced by afatinib.

Materials and methods: Patients diagnosed with non-small cell lung cancer who progressed to prior chemotherapy received 40 mg of afatinib. Malnutrition was determined by Subjective Global Assessment, and lean body mass (LBM) was determined by computed tomography scan analysis using a pre-established Hounsfield unit threshold. Toxicity was obtained during four cycles by Common Terminology Criteria for Adverse Events.

Results: Eighty-four patients were enrolled. Afatinib was administered as the second, third, and fourth line of treatment in 54.8%, 38.1%, and 7.12% of patients, respectively. Severe diarrhea, mucositis, and overall severe GT were present in 38.9%, 28.8%, and 57.5%, respectively. Of the patients, 50% developed dose-limiting toxicity (DLT). Patients with malnutrition have higher risk for severe GT. Patients with lower LBM and body mass index developed more DLT (71.4% vs. 18.8%).

Conclusion: Malnutrition is associated with a higher risk of severe GT induced by afatinib. Determination of nutritional status and body composition are helpful in identifying patients at higher risk of severe GT and could allow initiating treatment with lower doses according to tolerance.

Keywords: Afatinib; Gastrointestinal toxicity; Malnourishment; Non-small cell lung cancer; Nutritional status; Phase II trial.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Afatinib
  • Body Mass Index
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Female
  • Gastrointestinal Diseases / etiology*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Nutritional Status
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects*
  • Quinazolines / therapeutic use

Substances

  • Quinazolines
  • Afatinib