Gastrointestinal Disorders and Toxicities Induced By Anticancer Drugs. Another Risk Factor of Bleeding in Cancer-Associated Thrombosis
Authors: Janus Nicolas 
Published: November 2020

Introduction
Anticancer treatments has been changing since decades, evolving from chemotherapy (platinum salts) to recent check-point inhibitors. Nausea, vomiting and diarrhoea are common adverse events of anticancer drugs, despites the fact that some supportive care drugs can manage these adverse events. Gastro-intestinal (GI) disorders/toxicities are also important. Such as gastric/duodenal ulcer, gastritis, stomatitis, colitis, esophagitis... Cancer-associated-thrombosis (CAT) patients were also reported to be exposed to such GI disorders/toxicities and several publications recommended to consider these GI disorders/toxicities when choosing an anticoagulant in CAT (Carrier M. Curr Oncol 2018; Moik F. ESMO Open 2020). However, little is known about the nature of the anticancer drugs that CAT patients are receiving. The aim of this work was to check all the anticancer's SmPCs (Summary of Product Characteristics) on the EMA website for GI disorders.
Methods
All SmPCs of anticancer drugs indicated for lung cancer were checked on the EMA website. All adverse events regarding GI disorders/toxicities were collected. The frequency of adverse events used was the following: very common (≥ 1/10); common (≥ 1/100 to &lt; 1/10); uncommon (≥ 1/1,000 to &lt; 1/100); rare (≥ 1/10,000 to &lt; 1/1000); very rare (&lt; 1/10,000). However, it was decided to mainly focus on very common and common ones. Old anticancer drugs SmPCs (platinium salts...) were checked on electronic medicines compendium (medicines.org.uk), because these old SmPCs are not always available on the EMA website. Generics, biosimilars and drugs without a licence were excluded.
Results
Twenty-eight anticancer drugs were identified with a mix of traditional chemotherapies (platinum salts...), tyrosine kinase inhibitors (nib) and monoclonal antibodies (mab). Among these 28 anticancer drugs, 26 had at least one very common/common GI disorders/toxicities. Obviously, vomiting (82.1%) and diarrhoea (89.3%) are very well-known, but it was interesting to see that many anticancer drugs were associated with other very common/common GI toxicities such as stomatitis (71.4%) and colitis (10.7%). Additionally, several drugs (35.7%) were exposing to GI bleeding and/or GI perforation but these last adverse events were less common. Unfortunately, the SmPCs did not include data about the GI profile of the patients during the trials.
Conclusion
Monreal M et al reported in 1991 that acute gastroduodenal lesion was found in 21% of patients with venous thromboembolism, but there are no dedicated study about the incidence of GI disorders in CAT patients. This work reported that GI disorders/toxicities were common in anticancer drug's SmPCs. Consequently, it is important to be aware of this before initiating an anticoagulant treatment. However, this work had limitations. Indeed, these adverse events were reported in the SmPCs, based mainly on cancer trials and not on CAT trials. Furthermore, clinical trials and SmPCs may not always reflect the real clinical setting. Finally, lung cancer patients are usually receiving anticancer regimens that include several anticancer drugs, so the potential impact of GI disorders/toxicities from 2 or 3 anticancer drugs on a single patients could be greater. Nevertheless, it sounds reasonable to check for GI disorders/toxicities risks in order to initiate an adequate anticoagulant treatment in CAT patients and during follow-up.

Disclosures
Janus: Guerbet:Research Funding;B-Braun:Honoraria;LEO Pharma A/S:Current Employment, Honoraria;Fresenius Medical Care:Honoraria;Amgen:Honoraria, Research Funding;TEVA:Research Funding;Daichii-Sankyo:Honoraria, Research Funding;Roche:Honoraria, Research Funding;Vifor Pharma:Honoraria, Research Funding;Gilead:Honoraria, Research Funding;Novartis:Honoraria;Pierre Fabre Oncology:Research Funding;Bayer:Honoraria, Research Funding;Pfizer:Consultancy, Honoraria;IPSEN:Honoraria.