Phase III Study of Weekly High-Dose Infusional Fluorouracil Plus Folinic Acid With or Without Irinotecan in Patients With Metastatic Colorectal Cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986

Köhne, Claus Henning; Cutsem, Éric Van; Wils, J.; Bokemeyer, Carsten; El-Serafi, M.; Lutz, Manfred P.; Lorenz, M; Reichardt, Peter; Rückle-Lanz, H.; Frickhofen, N.; Fuchs, Roland J.; Mergenthaler, H.-G.; Langenbuch, T.; Vanhoefer, U.; Rougier, P; Voigtmann, R.; Müller, Lutz; Génicot, Bruno; Anak, Özlem; Nordlinger, Bernard

doi:10.1200/jco.2005.05.546

Cited by 306 publications

(152 citation statements)

References 31 publications

(8 reference statements)

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“…Two European trials investigated infusional 5-FU/FA regimens (de Gramont and Arbeitsgemeinschaft Internische Onkologie (AIO)); (Douillard et al, 2000;Köhne et al, 2005), whereas a US trial investigated a bolus 5-FU/FA regimen (Saltz et al, 2000). Irinotecan in combination with the bolus 5-FU/FA regimen was subsequently shown to be associated with high 60-day mortality levels (Sargent et al, 2001) and is now generally the less favoured way of administering this combination.…”

Section: Irinotecan In the First-line Treatment Of Advanced Crcmentioning

confidence: 99%

“…The addition of irinotecan to 5-FU/FA, irrespective of regimen, conferred a significant clinical benefit, in terms of RR (35 vs 22, 39 vs 21, 54 vs 32%), progression-free survival (PFS: 6.7 vs 4.4, 7.0 vs 4.3, 8.5 vs 6.4 months) and overall survival (17.4 vs 14.1, 14.8 vs 12.6, 20.1 vs 16.9 months) compared with the corresponding 5-FU/ FA regimen alone (respectively for Douillard et al, 2000;Saltz et al, 2000;Köhne et al, 2005). Also, although the more recent phase III study of Köhne et al, failed to demonstrate a statistically significant improvement in overall survival, the trend of 43 months increase led to one of the longest median overall survival times, to date, in this clinical setting.…”

Section: Irinotecan In the First-line Treatment Of Advanced Crcmentioning

confidence: 99%

“…The FOLFIRI/FOLFOX crossover in the Tournigand study achieved the longest survival recorded to date, for a phase III trial in advanced CRC. An interesting question is how much did crossover therapy contribute to the clinically significant benefits in survival of over 2 -3 months reported for the phase III trials of irinotecan/5-FU/FA in the first-line setting (Douillard et al, 2000;Saltz et al, 2000;Köhne et al, 2005)?…”

Section: The Influence Of Second-line Therapy On Survivalmentioning

confidence: 99%

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Management of advanced colorectal cancer: state of the art

Saunders

Iveson

2006

Br J Cancer

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Colorectal cancer (CRC) caused over 500 000 deaths worldwide in 2002. Recent advances in the treatment of advanced disease include the incorporation of two new cytotoxic agents, irinotecan and oxaliplatin, into first-line regimens. The concept of planned sequential therapy involving three active agents during the course of a patient's treatment is evolving. Coupled with the integrated use of targeted monoclonal antibodies, we can now expect overall survival rates for advanced disease to exceed 20 months. This review considers current treatments and suggests where future progress may occur.

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Section: Irinotecan In the First-line Treatment Of Advanced Crcmentioning

confidence: 99%

Section: Irinotecan In the First-line Treatment Of Advanced Crcmentioning

confidence: 99%

Section: The Influence Of Second-line Therapy On Survivalmentioning

confidence: 99%

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Management of advanced colorectal cancer: state of the art

Saunders

Iveson

2006

Br J Cancer

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“…However, only one-fourth of patients with metastases confined to the liver are surgical candidates due to tumor size, distribution or accessibility. 3,4 The mainstay of nonsurgical treatment for advanced colorectal cancer has been 5-fluorouracil (5-FU), and current chemotherapeutic regimens generally consist of 5-FU/leucovorin (folate) combined with newer agents, such as CPT-11 5,6 or oxaliplatin. 7,8 Nonetheless, whereas early-stage, organ-confined disease is associated with a good prognosis, the 5-year survival rate is still extremely poor for advanced colorectal cancer defined by the presence of metastatic disease.…”

Section: Introductionmentioning

confidence: 99%

Targeted delivery of a suicide gene to human colorectal tumors by a conditionally replicating vaccinia virus

et al. 2008

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We have generated a thymidine kinase gene-deleted vaccinia virus (VV) (Copenhagen strain) that expressed the fusion suicide gene FCU1 derived from the yeast cytosine deaminase and uracil phosphoribosyltransferase genes. Intratumoral inoculation of this thymidine kinase genedeleted VV encoding FCU1 (VV-FCU1) in the presence of systemically administered prodrug 5-fluorocytosine (5-FC) produced statistically significant reductions in the growth of subcutaneous human colon cancer in nude mice compared with thymidine kinase gene-deleted VV treatments or with control 5-fluorouracil alone. A limitation of prodrug therapies has often been the requirement for the direct injection of the virus into relatively large, accessible tumors. Here we demonstrate vector targeting of tumors growing subcutaneously following systemic administration of VV-FCU1. More importantly we also demonstrate that the systemic injection of VV-FCU1 in nude mice bearing orthotopic liver metastasis of a human colon cancer, with concomitant administration of 5-FC, leads to substantial tumor growth retardation. In conclusion, the insertion of the fusion FCU1 suicide gene potentiates the oncolytic efficiency of the thymidine kinase gene-deleted VV and represents a potentially efficient means for gene therapy of distant metastasis from colon and other cancers.

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“…Despite recent advancements in chemotherapy strategies for the treatment of advanced CRC patients, surgical resection of CRLM has been established as the treatment of choice and is the most effective and potentially curative therapy 6, 7, 8, 9, 10. Furthermore, surgical resection for CRLM combined with systemic adjuvant chemotherapy has a potential benefit to be curative for CRLM patients 11, 12.…”

Section: Introductionmentioning

confidence: 99%

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

Hirata

Ishiyama

Tanaka

et al. 2018

Annals of Gastroent Surgery

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AimWe investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells.MethodsWe classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences.ResultsThere were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural‐killer group 2, member D (NKG2D)‐ positive NK cells in PBMC and percentage of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐, NKp30‐, and signal regulatory protein β (SIRPβ)‐positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRPβ in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)‐2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups.ConclusionColorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients.

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Phase III Study of Weekly High-Dose Infusional Fluorouracil Plus Folinic Acid With or Without Irinotecan in Patients With Metastatic Colorectal Cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986

Cited by 306 publications

References 31 publications

Management of advanced colorectal cancer: state of the art

Management of advanced colorectal cancer: state of the art

Targeted delivery of a suicide gene to human colorectal tumors by a conditionally replicating vaccinia virus

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

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