Assessment of diarrhea as side effect of oral targeted antineoplastic agents in clinical practice



Diarrhea is one of the most frequent class adverse events associated with targeted oral antineoplastic agents (OAAs). Our objective was to analyze the incidence, characteristics, and severity of diarrhea in cancer patients in clinical practice.


An observational, longitudinal, and prospective study of cancer outpatients treated with targeted OAAs was carried out in a tertiary hospital. Targed OAAs analyzed were anaplastic lymphoma kinase inhibitors, BCR-ABL inhibitors, cyclin-dependent kinase inhibitors, epidermal growth factor receptor inhibitors, mTOR inhibitors, poly (ADP-ribose) polymerase inhibitors, and vascular endothelial growth factor receptor inhibitors. Patients were given a data collection form to record daily the number, severity (CTCAE version 5.0), and characteristics of stools during the first 30 days of treatment with OAAs. Multivariate analysis was performed to identify risk factors associated with the incidence of diarrhea.


We analyzed 240 patients, of whom 28.7% experienced diarrhea (25.4% grades 1–2 and 3.3% grades 3–4). Patients treated with EGFR and VEGFR inhibitors had a higher incidence of diarrhea. The multivariate analysis revealed that taking the OAA with food was associated with a lower risk of diarrhea (OR = 0.404 [0.205–0.956], p = 0.038).


More than a third of patients in treatment with OAAs presented diarrhea (any grade), and 22.1% of stools were semi-liquid/liquid. In multivariate analysis, taking the OAA on an empty stomach was associated with a statistically significant increase in the incidence of diarrhea.

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Author information




Dr. Martín and Dr. Escudero-Vilaplana conceived the idea. Dr. Escuero-Vilaplana, Dr. Collado-Borrell, Dr. del Monte-Millán, Dr. Gómez, Dr. Revuelta-Herrero, Dr. Hoyo-Muñoz, Dr. Marzal-Alfaro, Dr. Gonzalez-Haba, Dr. Lopez-Tarruella, and Dra. Jerez performed the measurements and collected the data. Dr. Herranz, Dr. Sanjurjo, and Dr. Martín were involved in planning and supervised the work. Dr. Escudero-Vilaplana, Dr. Collado-Borrell, and Dr. del Monte-Millán processed the experimental data, performed the analysis, drafted the manuscript, and designed the figures. Dr. Martín, Dr. Herranz, and Dr. Sanjurjo aided in interpreting the results and worked on the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Vicente Escudero-Vilaplana.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the local ethics committee (study code MMJ-ITK-2013-01) and conducted in accordance with the ethical principles of the Declaration of Helsinki. Patients signed an informed consent before entering the study and for publication.

Consent for publication

Patients signed an informed consent before entering the study and for publication.

Conflict of interest

Dr. Escudero-Vilaplana received support to continuing education/advisory fees from Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Ipsen Pharma, Janssen and Merck Sharp & Dohme, Novartis, and Pfizer, outside the submitted work.

Dr. Collado-Borrell received support to continuing education/advisory fees from Boehringer ingelheim, Hoffmann-La Roche, Bristol-Myers Squibb, Janssen Cilag, and Pfizer, outside the submitted work.

Dr. Marzal-Alfaro received support to continuing education/advisory fees from Roche, Abbvie, Pfizer, and Bayer Hispania, outside the submitted work.

Dr. Gonzalez-Haba received support to advisory fees from Bayer, Bristol-Myers Squibb, and Novartis, outside the submitted work.

Dr. Lopez-Tarruella Cobo has received consulting/advisory fees from Celgene, Novartis, Pierre Fabre, Pfizer, Roche, Astra-Zeneca, Eisai, Daiichi-Sankyo, and Lilly and speakers’ honoraria from Lilly, Novartis, and Pfizer, outside the submitted work.

Dr. Jerez Gilarranz has a consultant or advisory role at Novartis, Pfizer, Roche, and AstraZeneca and has received speaker honoraria from Roche, Novartis, and AstraZeneca and travel grants from Roche, Novartis, Pfizer, and Teva.

Dr. Herranz reported honorary/advisory fees from Astellas, Janssen, Kern, and Novartis, outside the submitted work.

Dr. Martin has received research grants from Roche, PUMA, and Novartis; consulting/advisory fees from AstraZeneca, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology, Daiichi Sankyo, and Pfizer; and speakers’ honoraria from AstraZeneca, Lilly, Amgen, Roche/Genentech, Novartis, and Pfizer, outside the submitted work.

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Escudero-Vilaplana, V., Collado-Borrell, R., del Monte-Millán, M. et al. Assessment of diarrhea as side effect of oral targeted antineoplastic agents in clinical practice. Support Care Cancer (2021).

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  • Diarrhea
  • Oral antineoplastic agent
  • Safety
  • Side effect
  • Toxicity