Increase of Survival Benefit in Advanced Resectable Colon Cancer by Extent of Adjuvant Treatment

Link, K. H.; Kornmann, Marko; Staib, Ludger; M, Redenbacher; Kron, Martina; Beger, H. G.

doi:10.1097/01.sla.0000171033.65639.a9

Cited by 38 publications

(37 citation statements)

References 29 publications

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“…Based on the results of our FOGT1 adjuvant trial demonstrating that addition of FA to infusional FU markedly increased 5-year OS in locally advanced CC [3], our study group planned the present trial using infusional FU and FA as the best standard treatment. The duration of adjuvant treatment was reduced from 12 to 6 months and oral levamisole was omitted as recommended at that time [3,4].…”

Section: Discussionmentioning

confidence: 99%

“…In a former trial [3], our group had proven that 12-month adjuvant treatment using FUFA + levamisole was superior to FU + levamisole. Levamisole was considered to be ineffective, and a treatment duration of 6 months was judged to be equivalent to 12 months [4,5,6].…”

Section: Methodsmentioning

confidence: 99%

“…For sample size estimation the following assumptions were made: The 5-year OS rate of FUFA was estimated to be 70% [3], and the 5-year OS rate of the more toxic Folfiri combination should be 10 percent points higher compared to FUFA. The power of the study was 80%, and the level of significance was 2.5% (one-sided).…”

Section: Methodsmentioning

confidence: 99%

“…Its administration in lymph node-positive CC (Union for International Cancer Control (UICC) stage III) was estimated to reduce the relative risk of death by 26% compared to surgery alone [2]. Modulation of FU using folinic acid (FA) further improved its benefit [3], while modulation using levamisole was judged to be ineffective [4,5]. Several trials focusing on the duration of treatment revealed that 6-8 months may be as effective as 12 months [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…With the knowledge of the results of the largest German adjuvant trial in CC in mind [3], we designed a randomized phase III multicenter trial with the aim to improve OS in locally advanced CC. Standard adjuvant FUFA treatment was intensified by addition of irinotecan.…”

Section: Introductionmentioning

confidence: 99%

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Adjuvant Chemotherapy of Locally Advanced Colon Cancer: Final Results of a Randomized Trial Comparing 5-Fluorouracil and Folinic Acid with Folfiri

Paschke

Hebart²,

Goeb

et al. 2018

Visc Med

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Background: There is still the need to optimize adjuvant treatment of colon cancer (CC). Standard adjuvant chemotherapy using 5-fluorouracil (FU) and folinic acid (FA) was compared with a combination including irinotecan (Folfiri). The aim of the present report was to analyze overall survival (OS) after long-term follow-up, to summarize final recurrence rates and toxicity data, and to identify possible clinical and pathological factors associated with prognosis. Methods: Patients (CC stage IIb and III) were randomized to a 6-month treatment with FUFA or Folfiri. The trial was closed after 275 of 588 planned patients, 269 of which were included in the intention-to-treat analysis. Results: 133 and 136 patients received FUFA and Folfiri, respectively. Adjuvant therapy was not completed for 16 FUFA (12.0%) and 44 Folfiri (32.4%) patients. Toxicities grade III and IV were observed in 17 (12.8%) patients treated with FUFA and in 50 (36.8%) patients treated with Folfiri. Recurrences occurred in 46 of 133 (34.6%) and in 47 of 136 (34.6%) patients who received FUFA and Folfiri, respectively. 5-year OS rates were 69.9% (95% confidence interval (CI): 61.2-77.1) for FUFA and 72.7% (95% CI: 63.9-79.8) for Folfiri. OS was associated with tumor grading (1 & 2 vs. 3), tumor sub-stage (II vs. IIIa vs. IIIb vs. IIIc), and tumor location (left vs. right colon). Conclusion: Folfiri cannot be generally recommended for adjuvant chemotherapy of CC. Besides tumor grading and sub-staging, prognosis of CC may depend on tumor location. Left-sided tumors had a significantly better prognosis irrespective of treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Adjuvant Chemotherapy of Locally Advanced Colon Cancer: Final Results of a Randomized Trial Comparing 5-Fluorouracil and Folinic Acid with Folfiri

Paschke

Hebart²,

Goeb

et al. 2018

Visc Med

Self Cite

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Scientific Surgery

2006

British Journal of Surgery

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Natural killer cell‐mediated ablation of metastatic liver tumors by hydrodynamic injection of IFNα gene to mice

Takehara

Uemura

Tatsumi

et al. 2006

Intl Journal of Cancer

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Interferon (IFN) a is a pleiotropic cytokine acting as an antiviral substance, cell growth inhibitor and immunomodulator. To evaluate the therapeutic efficacy and mechanisms of IFNa on hepatic metastasis of tumor cells, we hydrodynamically injected naked plasmid DNA encoding IFNa1 (pCMV-IFNa1) into Balb/cA mice having 2 days hepatic metastasis of CT-26 cells. Single injection of pCMV-IFNa1 efficiently enhanced the natural killer (NK) activity of hepatic mononuclear cells, induced production of IFNc in serum and led to complete rejection of tumors in the liver. Mice protected from hepatic metastasis by IFNa therapy displayed a tumor-specific cytotoxic T cell response and were resistant to subcutaneous challenge of CT-26 cells. NK cells were critically required for IFNa-mediated rejection of hepatic metastasis, because their depletion by injecting anti-asialo GM1 antibody completely abolished the antimetastatic effect. To find whether NK cells are directly activated by IFNa and are sufficient for the antimetastatic effect, the responses to IFNa were examined in SCID mice lacking T cells, B cells and NKT cells. IFNa completely rejected hepatic metastasis in SCID mice and efficiently activated SCID mononuclear cells, as evidenced by activation of STAT1 and a variety of genes, such as MHC class I, granzyme B, tumor necrosis factorrelated apoptosis-inducing ligand and IFNc, and also enhanced Yac1 lytic ability. Study of IFNc knockout mice revealed that IFNc was not necessary for IFNa-mediated NK cell activation and metastasis protection. In conclusion, IFNa efficiently activates both innate and adaptive immune responses, but NK cells are critically required and sufficient for IFNa-mediated initial rejection of hepatic metastasis of microdisseminated tumors. ' 2006 Wiley-Liss, Inc.Key words: DNA; innate; adaptive; immunity NK The liver is the most common site of metastatic malignancy and the status of this organ is an important determinant of survival in patients with advanced disease. The risk of hepatic metastasis remains high in many patients after potentially curative surgery at primary sites.1 This suggests that the spread of tumor cells can occur in the liver even when they cannot be detected by current diagnostic modalities. To suppress the incidence of liver metastasis, whole liver therapy against microdisseminated tumors should be considered.2 Since the liver contains an abundance of immune cells, the cytokine-meditated activation of these cells may be a promising approach toward this end. 3,4 Interferon (IFN) a is a pleiotropic cytokine acting as an antiviral substance, cell growth inhibitor and immunomodulator. IFNa as well as IFNg are primarily induced in response to viral infection of cells and ligate a cognate receptor for the Type 1 IFN expressed on target cells. 5 On the other hand, Type 2 IFN, IFNg, is produced predominantly by T lymphocytes, natural killer (NK) cells and NKT cells and uses a distinct receptor. IFNa-mediated antiviral activity includes induction of 2 0 -5 0 oligoadenylate synthetases,...

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Increase of Survival Benefit in Advanced Resectable Colon Cancer by Extent of Adjuvant Treatment

Cited by 38 publications

References 29 publications

Adjuvant Chemotherapy of Locally Advanced Colon Cancer: Final Results of a Randomized Trial Comparing 5-Fluorouracil and Folinic Acid with Folfiri

Adjuvant Chemotherapy of Locally Advanced Colon Cancer: Final Results of a Randomized Trial Comparing 5-Fluorouracil and Folinic Acid with Folfiri

Scientific Surgery

Natural killer cell‐mediated ablation of metastatic liver tumors by hydrodynamic injection of IFNα gene to mice

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