Liver toxicity in colorectal cancer patients treated with first-line FOLFIRI-containing regimen: a single institution experience

Vincenzi, Bruno; Imperatori, Marco; Picardi, Antonio; Gentilucci, Umberto Vespasiani; Gallo, Paolo; Fausti, Valentina; Ceruso, Mariella Spalato; Santini, Daniele; Tonini, Giuseppe

doi:10.1586/14737140.2015.1061937

Cited by 15 publications

(24 citation statements)

References 31 publications

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“…Unfortunately, the overall response rate of 5-FU in advanced CRC is limited to 10-15% [45], although this can be improved in combination with other cytotoxic agents [46] including oxaliplatin or irinotecan, in the first line setting albeit with increased toxicity [45,46]. Since resistance to 5-FU remains a major cause of failure of chemotherapy [47], model systems to better understand patient response to 5-FU are required.…”

Section: Introductionmentioning

confidence: 99%

A Biobank of Colorectal Cancer Patient-Derived Xenografts

Abdirahman

Christie

Preaudet

et al. 2020

Cancers

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Colorectal cancer (CRC) is a challenging disease, with a high mortality rate and limited effective treatment options, particularly for late-stage disease. Patient-derived xenografts (PDXs) have emerged as an informative, renewable experimental resource to model CRC architecture and biology. Here, we describe the generation of a biobank of CRC PDXs from stage I to stage IV patients. We demonstrate that PDXs within our biobank recapitulate the histopathological and mutation features of the original patient tumor. In addition, we demonstrate the utility of this resource in pre-clinical chemotherapy and targeted treatment studies, highlighting the translational potential of PDX models in the identification of new therapies that will improve the overall survival of CRC patients.

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Section: Introductionmentioning

confidence: 99%

A Biobank of Colorectal Cancer Patient-Derived Xenografts

Abdirahman

Christie

Preaudet

et al. 2020

Cancers

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“…According to some reports, more than 60% of patients receiving postoperative adjuvant chemotherapy for gastrointestinal tumors experience gastrointestinal complication of grade II or higher. 23 , 24 On the contrary, our research shows that perioperative HIPEC patients do not experience a high incidence of gastrointestinal complication (28/201, 13.93%), but the incidence of concomitant hepatotoxicity among patients who underwent grade II or more gastrointestinal complication was significantly increased (22/28, 78.57%). Thus, concern must be raised on gastrointestinal complication during HIPEC treatment.…”

Section: Discussionmentioning

confidence: 59%

The incidence and risk factors of hepatotoxicity induced by perioperative hyperthermic intraperitoneal chemotherapy in gastrointestinal carcinoma patients: a retrospective study

Zheng

Xiong

et al. 2018

OTT

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AimTo investigate the incidence and risk factors of hepatotoxicity induced by perioperative hyperthermic intraperitoneal chemotherapy (HIPEC) in gastrointestinal carcinoma patients.Patients and methodsPatients with gastrointestinal cancers treated with surgery in the presence or absence of HIPEC at a single institution were retrospectively reviewed. The patients received the treatment of surgery + HIPEC or surgery alone. The incidence of hepatotoxicity induced by HIPEC was recorded and risk factors were analyzed.ResultsIn total, 301 eligible patients were included in the study, with 201 cases in the surgery + HIPEC group and 100 cases in the surgery group alone. The incidence of hepatotoxicity in the surgery + HIPEC group was higher than that in the surgery-alone group (57.71% vs 42%, P<0.05). In univariate analysis, HIPEC regimens, HIPEC techniques, HIPEC duration, and gastrointestinal complications were associated with the incidence of hepatotoxicity (P<0.05), while patient age, gender, tumor type, clinical stage, pathological type, blood transfusion, hepatitis B virus infection status, long-term alcohol use, and surgical techniques were not (P>0.05). Multivariate analysis showed that HIPEC regimen was the main risk factor of hepatotoxicity induced by HIPEC, with cisplatin + docetaxel being an independent risk factor of the HIPEC-induced hepatotoxicity. Open HIPEC techniques and HIPEC duration more than 60 minutes tend to increase the incidence of hepatotoxicity.ConclusionSurgery + HIPEC increases the incidence of hepatotoxicity. HIPEC regimen is the main risk factor for hepatotoxicity induced by HIPEC. Further prospective study is needed to confirm our conclusion.

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“…It was well-recognized that SN-38, the active metabolite of irinotecan, was inactivated by glucuronidation during hepatic metabolism and can lead to steatosis, and the combination of 5-FU and irinotecan can lead to rapid progression from simple steatosis to chemotherapy-associated steatohepatitis. 7,18,19 More importantly, due to narrow therapeutic window, hepatoxicity of irinotecan can be highly variable among recipients and vulnerable to drug interactions. For example, co-administration of valproic acid can increase incidence of liver injury by changing the disposition of irinotecan.…”

Section: Discussionmentioning

confidence: 99%

A simple method to identify undiagnosed drug-induced liver injury (DILI) and its application in oncology pharmacy practice

Wen

et al. 2019

J Oncol Pharm Pract

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Aims To establish a simple method to identify chemotherapy-induced liver injury among oncological patients. To evaluate current clinical approach to elevated laboratory liver test results. Methods A total of 289 patients admitted to oncology department who had systemic chemotherapy episodes for cancer treatment from 1 January 2017 to 31 December 2017 were identified. With aid of healthcare information system, Hy's law was applied to laboratory liver test results to identify potential hepatocellular drug-induced liver injury cases. Medical record review was carried out among identified patients to exclude liver dysfunction of alternative causes. Current clinical approach to elevated laboratory liver tests was evaluated through medical record review. Results Of 289 patients who were treated by systemic chemotherapies, there were 123 patients with elevated laboratory liver tests, among which 8 patients were suspected as potential Hy's law cases. After medical record review, there were two patients determined with chemotherapy-associated liver injury, caused by 5-fluorouracil, leucovorin, irinotecan, and S-1 plus paclitaxel separately. Of eight potential Hy's law cases, seven (87.5%) patients were prescribed with ≥2 kinds of liver protectants and remained treated with traditional Chinese medicine for decoction. Conclusions A reliable and simple method to identify undiagnosed drug-induced liver injury was successfully established. An annual incidence of 0.69% of chemotherapy-associated liver injury in oncology department of the setting was found.

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Liver toxicity in colorectal cancer patients treated with first-line FOLFIRI-containing regimen: a single institution experience

Abstract: FOLFIRI-based hepatotoxicity has been indirectly defined as a mixed pattern injury in all three regimens evaluated.

Cited by 15 publications

References 31 publications

A Biobank of Colorectal Cancer Patient-Derived Xenografts

A Biobank of Colorectal Cancer Patient-Derived Xenografts

The incidence and risk factors of hepatotoxicity induced by perioperative hyperthermic intraperitoneal chemotherapy in gastrointestinal carcinoma patients: a retrospective study

A simple method to identify undiagnosed drug-induced liver injury (DILI) and its application in oncology pharmacy practice

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