Gastrointestinal perforations in patients treated with erlotinib: A report of two cases with fatal outcome and literature review

Gass-Jégu, Florence; Gschwend, Anthony; Gairard-Dory, Anne-Cécile; Mennecier, B.; Tebacher-Alt, Martine; Gourieux, B.; Quoix, Élisabeth

doi:10.1016/j.lungcan.2016.06.012

Cited by 16 publications

(13 citation statements)

References 8 publications

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“…Erlotinib is a tyrosine kinase inhibitor, which drug interactions occur commonly because of DDIs concern absorption (incomplete drug absorption is a risk of drug interaction) and metabolization by the cytochrome P450 isozymes (30). Significant clinical consequences have been associated with these interaction mechanisms (8,31,32). Interaction between sunitinib and ondansetron or quinolones was found in the study which may result in an increased risk of QT interval prolongation.…”

Section: Discussionmentioning

confidence: 87%

“…For example, concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) and methotrexate may result in an increased risk of methotrexate toxicity, and fatal cases have been reported (6,7). Dual CYP3A4 and CYP1A2 inhibitor ciprofloxacin may result in increased erlo-tinib exposure and even lead to death (8). Patients receiving anti-cancer therapy are particularly vulnerable to DDIs because they often take numerous medications concurrently to manage their malignancy, toxicities, cancer-associated syndromes and other co-morbid illnesses.…”

Section: Introductionmentioning

confidence: 99%

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The Prevalence of the Potential Drug-Drug Interactions Involving Anticancer Drugs in China: A Retrospective Study

Wang¹,

Xiao²,

Liu³

et al. 2019

ijph

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Background: To survey the prevalence of potential drug-drug interactions (DDIs) between anticancer drugs and non-anticancer drugs and evaluate the risk factors associated with these drug-drug interactions in China. Methods: All discharged patients in the Department of Oncology were collected from Jun to Dec in 2016 with the Hospital Information System of the Chinese people’s Liberation Army General Hospital. Drugs were screened for interactions by Micromedex solutions database. Descriptive statistics were generated and logistic regression was used to identify the associated factors. Results: Among 6578 eligible patients, 1979 potential drug interactions were found in 1830 patients (27.82%). The most common drug-drug interaction was cisplatin and furosemide. Erlotinib was most likely to interact with various non-anticancer drugs. Most interactions were classified as pharmacodynamics (71.60%), major severity (97.02%) and were supported by fair documentation evidence (86.21%). In multivariate analysis, increasing number of medications, lung cancer and patients with stage IV had a higher risk for potential drug-drug interactions. Conclusion: Potential drug-drug interactions between antineoplastic drugs and non-antineoplastic drugs occur frequently in cancer patients of Chinese hospitals. Doctors should fully consider potential risk associated with DDIs. Further research should be performed to evaluate real clinical significance of these drug-drug interactions.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

The Prevalence of the Potential Drug-Drug Interactions Involving Anticancer Drugs in China: A Retrospective Study

Wang¹,

Xiao²,

Liu³

et al. 2019

ijph

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“…A retrospective series of 208 patients with NSCLC who received bevacizumab identified grade 3 diarrhea, febrile neutropenia, and stomatitis as risk factors for bevacizumab-associated perforation (16). Gastrointestinal perforation secondary to erlotinib, a first-generation EGFR inhibitor, is reported in two case reports (17,18), but there have been no reports of bowel perforation associated with osimertinib.…”

Section: Discussionmentioning

confidence: 99%

Cecal Volvulus as a Rare Complication of Osimertinib Dosed at 160 mg in Patients With EGFR-Mutant Non-small Cell Lung Cancer

et al. 2020

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Background: Osimertinib is a 3rd-generation tyrosine kinase inhibitor (TKI) that blocks the epidermal growth factor receptor (EGFR) in non-small lung cancer (NSCLC) and has dramatically improved outcomes for patients with EGFR mutations. While gastrointestinal complications such as diarrhea have been reported with EGFR inhibitors (due to off-target interactions with EGFR receptors within the gut lining), cecal volvulus is an extremely rare complication in advanced malignancy. To date, there are no reported cases associating cecal volvulus with any EGFR TKIs.Case Presentation: In this case series, we present three cases of cecal volvulus among patients with EGFR-positive NSCLC patients treated with osimertinib dosed at double the standard 80 mg dose (160 mg daily). No patient was receiving concurrent chemotherapy or bevacizumab at the time of this described complication. In two cases where pathology was available for review, peritoneal carcinomatosis or intra-abdominal spread was not observed. In a retrospective evaluation of 101 patients treated with osimertinib in our institution, there was a statistically significant difference in the incidence of cecal volvulus among patients receiving osimertinib at 160 mg vs. patients receiving the 80 mg dose (27 vs. 0%; p < 0.001).Conclusions: To our knowledge, these are the first cases to highlight a potentially important and serious gastrointestinal complication associated with the 160 mg dose of osimertinib.

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“…In our case, crizotinib produced marked tumor regression within a few days. There are two reported cases of EGFR-tyrosine kinase inhibitor (TKI) associated GI perforation without GI metastasis ( 6 , 7 ). ALK inhibitor has similar characteristics to EGFR TKI, which is known for the rapid onset of its action.…”

Section: Discussionmentioning

confidence: 99%

Crizotinib-induced Rectal Perforation with Abscess

et al. 2017

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An 86-year-old Japanese man was diagnosed with stage IV lung adenocarcinoma. The patient was treated with crizotinib after echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement was detected from his pleural effusion. He subsequently developed abdominal pain and rebound tenderness in the right lower abdomen. Contrast-enhanced abdominal CT showed a low-density area in the abdominal cavity. The size of the abscess was decreased by drainage and the administration of antibiotics. Fistulography revealed a fistula from the rectum to the abscess, and a diagnosis of lower intestinal tract perforation with abscess formation was made. Crizotinib was discontinued and treatment with alectinib was initiated. The patient remains under treatment as an outpatient at our department without adverse effects.

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Gastrointestinal perforations in patients treated with erlotinib: A report of two cases with fatal outcome and literature review

Cited by 16 publications

References 8 publications

The Prevalence of the Potential Drug-Drug Interactions Involving Anticancer Drugs in China: A Retrospective Study

The Prevalence of the Potential Drug-Drug Interactions Involving Anticancer Drugs in China: A Retrospective Study

Cecal Volvulus as a Rare Complication of Osimertinib Dosed at 160 mg in Patients With EGFR-Mutant Non-small Cell Lung Cancer

Crizotinib-induced Rectal Perforation with Abscess

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