Irinotecan- <i>vs </i>oxaliplatin-based regimens for neoadjuvant chemotherapy in colorectal liver metastasis patients: A retrospective study

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Abstract

BACKGROUND

Neoadjuvant chemotherapy (NC) improves the survival outcomes of selected patients with colorectal liver metastasis (CRLM). The benefits of irinotecan-based regimens in these patients are still under debate.

AIM

To compare the benefits of irinotecan- and oxaliplatin-based regimens in patients with resectable CRLM.

METHODS

From September 2003 to August 2020, 554 patients received NC and underwent hepatectomy for CRLM. Based on a 1:1 propensity score matching (PSM) model, 175 patients who received irinotecan were matched to 175 patients who received oxaliplatin to obtain two balanced groups regarding demographic, therapeutic, and prognostic characteristics.

RESULTS

Chemotherapy was based on oxaliplatin in 353 (63.7%) patients and irinotecan in 201 (36.3%). After PSM, the 5-year progression-free survival (PFS) and overall survival (OS) rates with irinotecan were 18.0% and 49.7%, respectively, while the 5-year PFS and OS rates with oxaliplatin were 26.0% and 46.8%, respectively. Intraoperative blood loss, operating time, and postoperative complications differed significantly between the two groups. In the multivariable analysis, carbohydrate antigen 19-9, RAS mutation, response to NC, tumor size > 5 cm, and tumor number > 1 were independently associated with PFS.

CONCLUSION

In NC in patients with CRLM, irinotecan is similar to oxaliplatin in survival outcomes, but irinotecan is superior regarding operating time, intraoperative blood loss, and postoperative complications.

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Most cited references 24

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There is a need for clearly defined and widely applicable clinical criteria for the selection of patients who may benefit from hepatic resection for metastatic colorectal cancer. Such criteria would also be useful for stratification of patients in clinical trials for this disease. Clinical, pathologic, and outcome data for 1001 consecutive patients undergoing liver resection for metastatic colorectal cancer between July 1985 and October 1998 were examined. These resections included 237 trisegmentectomies, 394 lobectomies, and 370 resections encompassing less than a lobe. The surgical mortality rate was 2.8%. The 5-year survival rate was 37%, and the 10-year survival rate was 22%. Seven factors were found to be significant and independent predictors of poor long-term outcome by multivariate analysis: positive margin (p = 0.004), extrahepatic disease (p = 0.003), node-positive primary (p = 0.02), disease-free interval from primary to metastases 1 (p = 0.0004), largest hepatic tumor >5 cm (p = 0.01), and carcinoembryonic antigen level >200 ng/ml (p = 0.01). When the last five of these criteria were used in a preoperative scoring system, assigning one point for each criterion, the total score was highly predictive of outcome (p < 0.0001). No patient with a score of 5 was a long-term survivor. Resection of hepatic colorectal metastases may produce long-term survival and cure. Long-term outcome can be predicted from five criteria that are readily available for all patients considered for resection. Patients with up to two criteria can have a favorable outcome. Patients with three, four, or five criteria should be considered for experimental adjuvant trials. Studies of preoperative staging techniques or of adjuvant therapies should consider using such a score for stratification of patients.

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Irinotecan is active against colorectal cancer in patients whose disease is refractory to fluorouracil. We investigated the efficacy of these two agents combined for first-line treatment of metastatic colorectal cancer. 387 patients previously untreated with chemotherapy (other than adjuvant) for advanced colorectal cancer were randomly assigned open-label irinotecan plus fluorouracil and calcium folinate (irinotecan group, n=199) or fluorouracil and calcium folinate alone (no-irinotecan group, n=188). Infusion schedules were once weekly or every 2 weeks, and were chosen by each centre. We assessed response rates and time to progression, and also response duration, survival, and quality of life. Analyses were done on the intention-to-treat population and on evaluable patients. The response rate was significantly higher in patients in the irinotecan group than in those in the no-irinotecan group (49 vs 31%, p<0.001 for evaluable patients, 35 vs 22%, p<0.005 by intention to treat). Time to progression was significantly longer in the irinotecan group than in the no-irinotecan group (median 6.7 vs 4.4 months, p<0.001), and overall survival was higher (median 17.4 vs 14.1 months, p=0.031). Some grade 3 and 4 toxic effects were significantly more frequent in the irinotecan group than in the no-irinotecan group, but effects were predictible, reversible, non-cumulative, and manageable. Irinotecan combined with fluorouracil and calcium folinate was well-tolerated and increased response rate, time to progression, and survival, with a later deterioration in quality of life. This combination should be considered as a reference first-line treatment for metastatic colorectal cancer.

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Author and article information

Contributors

Wei Liu

Feng-Lin Chen

Kun Wang

Quan Bao

Hong-Wei Wang

Ke-Min Jin

Bao-Cai Xing

Journal

Journal ID (nlm-ta): World J Gastrointest Surg

Journal ID (publisher-id): WJGS

Title: World Journal of Gastrointestinal Surgery

Publisher: Baishideng Publishing Group Inc

ISSN (Electronic): 1948-9366

Publication date (Print): 27 September 2022

Publication date (Electronic): 27 September 2022

Volume: 14

Issue: 9

Pages: 904-917

Affiliations

Department of Hepatopancreatobiliary Surgery, Peking University School of Oncology, Beijing Cancer Hospital, Beijing 100142, China

Department of Hepatopancreatobiliary Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, China

Author notes

Author contributions: Liu W designed and performed the research and wrote the paper; Xing BC designed the research and supervised the report; Chen FL designed the research and contributed to the analysis; Wang K, Bao Q, Wang HW, and Jin KM provided clinical advice and reviewed the manuscript; and all authors have read and approved the final version.

Supported by the National Nature Science Foundation of China, No. 81874143 and No. 31971192; and Beijing Hospitals Authority Youth Program, No. QMS20201105.

Corresponding author: Bao-Cai Xing, Department of Hepatopancreatobiliary Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, No. 52 Fucheng Road, Haidian District, Beijing 100142, China. xingbaocai88@ 123456sina.com

Article

Other ID: jWJGS.v14.i9.pg904

DOI: 10.4240/wjgs.v14.i9.904

PMC ID: 9521480

SO-VID: ecdaeb17-8326-4978-8f83-25c59ae6e7b3

License:

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

History

Date received : 3 March 2022

Date revision received : 28 April 2022

Date accepted : 26 August 2022

Irinotecan- vs oxaliplatin-based regimens for neoadjuvant chemotherapy in colorectal liver metastasis patients: A retrospective study

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Abstract

BACKGROUND

AIM

METHODS

RESULTS

CONCLUSION

Related collections

Karger: Oncology

Most cited references 24

Global cancer statistics, 2012.

Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases.

Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial.

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