Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial

Nordlinger, Bernard; Sørbye, Halfdan; Glimelius, Bengt; Poston, Graeme J.; Schlag, Peter M.; Rougier, Philippe; Bechstein, Wolf O.; Primrose, John; Walpole, Euan; Finch-Jones, Meg; Jaeck, Daniel; Mirza, D.; Parks, Rowan W.; Mauer, Murielle; Tanis, E.; Cutsem, Éric Van; Scheithauer, Werner; Gruenberger, Thomas

doi:10.1016/s1470-2045(13)70447-9

Cited by 1,065 publications

(757 citation statements)

References 16 publications

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“…The final results for the secondary endpoint of overall survival were presented at the 2012 annual meeting of American Society of Clinical Oncology (ASCO). The addition of perioperative chemotherapy to resection led to no significant improvement in long term survival (HR 0.87, 0.66-1.14, p = 0.303), but there was a mere 4% improvement in the FOLFOX4 arm after 5-years (25). Perioperative FOLFOX therapy is considered a highrisk chemotherapeutic regimen in terms of safety.…”

Section: Discussionmentioning

confidence: 99%

A combination of oral uracil-tegafur plus leucovorin (UFT + LV) is a safe regimen for adjuvant chemotherapy after hepatectomy in patients with colorectal cancer: Safety report of the UFT/LV study

Saiura¹,

Yamamoto²,

Hasegawa³

et al. 2014

DD&T

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Section: Discussionmentioning

confidence: 99%

A combination of oral uracil-tegafur plus leucovorin (UFT + LV) is a safe regimen for adjuvant chemotherapy after hepatectomy in patients with colorectal cancer: Safety report of the UFT/LV study

Saiura¹,

Yamamoto²,

Hasegawa³

et al. 2014

DD&T

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“…Dieser wurde in einem systematischen Review [1083], mit überwiegend retrospektiven kontrollierten Beobachtungsstudien, einer randomisierten Studie [1084,1085] sowie mehreren nicht kontrollierten Analysen untersucht. Insgesamt ist kein Einfluss auf das Gesamtüberleben (OS) nachweisbar.…”

Section: Hintergrundunclassified

S3-Leitlinie – Kolorektales Karzinom

Schmiegel

Buchberger

Follmann³

et al. 2017

Z Gastroenterol

148

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“…5-7 Unfortunately, surgical resection of isolated liver metastases of CRC (LM-CRC) is curative in only 20%-30% of patients, 8 , 9 and systemic therapy provides limited survival benefit. 10 Patients with unresectable LM-CRC have a poor prognosis with a median survival of only two years. 11 Therefore, there is a pressing need for more effective therapeutic strategies for LM-CRC.…”

Section: Introductionmentioning

confidence: 99%

Blockade of LAG3 enhances responses of tumor-infiltrating T cells in mismatch repair-proficient liver metastases of colorectal cancer

et al. 2018

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Purpose: Liver metastasis develops in >50% of patients with colorectal cancer (CRC), and is a leading cause of CRC-related mortality. We aimed to identify which inhibitory immune checkpoint pathways can be targeted to enhance functionality of intra-tumoral T-cells in mismatch repair-proficient liver metastases of colorectal cancer (LM-CRC). Methodology: Intra-tumoral expression of multiple inhibitory molecules was compared among mismatch repair-proficient LM-CRC, peritoneal metastases of colorectal cancer (PM-CRC) and primary CRC. Expression of inhibitory molecules was also analyzed on leukocytes isolated from paired resected metastatic liver tumors, tumor-free liver tissues, and blood of patients with mismatch repair-proficient LM-CRC. The effects of blocking inhibitory pathways on tumor-infiltrating T-cell responses were studied in ex vivo functional assays. Results: Mismatch repair-proficient LM-CRC showed higher expression of inhibitory receptors on intra-tumoral T-cells and contained higher proportions of CD8+ T-cells, dendritic cells and monocytes than mismatch repair-proficient primary CRC and/or PM-CRC. Inhibitory receptors LAG3, PD-1, TIM3 and CTLA4 were higher expressed on CD8+ T-cells, CD4+ T-helper and/or regulatory T-cells in LM-CRC tumors compared with tumor-free liver and blood. Antibody blockade of LAG3 or PD-L1 increased proliferation and effector cytokine production of intra-tumoral T-cells isolated from LM-CRC in response to both polyclonal and autologous tumor-specific stimulations. Higher LAG3 expression on intra-tumoral CD8+ T-cells associated with longer progression-free survival of LM-CRC patients. Conclusion: Mismatch repair-proficient LM-CRC may be more sensitive to immune checkpoint inhibitors than mismatch repair-proficient primary CRC. Blocking LAG3 enhances tumor-infiltrating T-cell responses of mismatch repair-proficient LM-CRC, and therefore may be a new promising immunotherapeutic target for LM-CRC.

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Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial

Cited by 1,065 publications

References 16 publications

A combination of oral uracil-tegafur plus leucovorin (UFT + LV) is a safe regimen for adjuvant chemotherapy after hepatectomy in patients with colorectal cancer: Safety report of the UFT/LV study

A combination of oral uracil-tegafur plus leucovorin (UFT + LV) is a safe regimen for adjuvant chemotherapy after hepatectomy in patients with colorectal cancer: Safety report of the UFT/LV study

S3-Leitlinie – Kolorektales Karzinom

Blockade of LAG3 enhances responses of tumor-infiltrating T cells in mismatch repair-proficient liver metastases of colorectal cancer

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