Clinical determinants of survival in patients with 5-fluorouracil- based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients

Ch, Köhne; Cunningham, David; Costanzo, Francesco Di; Glimelius, Bengt; Blijham, Geert H.; Aranda, Enrique; Scheithauer, Werner; Rougier, Philippe; Palmer, Michael K; Wils, J.; Baron, B.; Pignatti, Francesco; Schöffski, Patrick; Micheel, S.; Hecker, Hartmut

doi:10.1093/annonc/mdf034

Cited by 433 publications

(266 citation statements)

References 38 publications

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“…23,39 Whilst it is possible that increasing neutrophil count is simply an epiphenomenon of the inflammatory response in the vicinity of the tumour, the emerging theory of 'immune enhancement' suggests that cells of the myeloid lineage, particularly neutrophils, are recruited from the circulation and play a direct role in promoting aggressive tumour phenotypes. 8,9 Neutrophils are the major producers of a number of ligands that may induce tumour cell proliferation and invasion, including transforming growth factor-.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases

Neal¹,

Mann²,

Sutton³

et al. 2009

European Journal of Cancer

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Background: There is increasing evidence that the presence of a preoperative systemic inflammatory response (SIR) independently predicts poor long-term outcome in patients with colorectal cancer (CRC).Socioeconomic deprivation was reported to correlate with the presence of the SIR and to itself independently predict poor outcome following primary CRC resection. The aim of this study was to determine the prognostic value of preoperative systemic inflammatory biomarkers and socioeconomic deprivation in patients undergoing resection of colorectal liver metastases (CLM) and to examine correlations between these variables in this context. Results: On multivariable analysis, poor CRS (3-5), high neutrophil count (>6.0 x10 9 /L) and low serum albumin (<40 g/dL) were the only independent predictors of shortened overall survival following metastasectomy, with neutrophil count representing the greatest relative risk of death. These factors were also the only independent predictors of shortened disease-free survival 3 following hepatectomy. Socioeconomic deprivation was associated with neither systemic inflammation nor long-term outcome in this context. Patients and methods: Conclusions:The presence of a preoperative systemic inflammatory response, but not socioeconomic deprivation, independently predicts shortened survival following resection of CLM.4

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Section: Discussionmentioning

confidence: 99%

“…2,13,20,23,26,31,39 For simplicity, high numbers of cells indicates cell numbers higher than the cut-off levels and low numbers of cells indicates cell numbers lower than the cut-off levels. Carstairs deprivation scores were analysed following allocation into established UK-based score quintiles.…”

Section: Statisticsmentioning

confidence: 99%

Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases

Neal¹,

Mann²,

Sutton³

et al. 2009

European Journal of Cancer

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“…Studies in patients with metastatic colorectal cancer showed that carriers of the TS 5 0 -UTR 3R (3G) and/or the TS 3 0 -UTR 6 þ alleles had adverse clinical outcomes (Pullarkat et al, 2001;Etienne et al, 2002;Park et al, 2002;Marcuello et al, 2004;Stoehlmacher et al, 2004;Martinez-Balibrea et al, 2007); however, such an association was not always detected (Lecomte et al, 2004;Jakobsen et al, 2005;Ruzzo et al, 2007a, b). Heterogeneity in clinical experimental conditions (Sorbye et al, 2007), in tumour burden (Köhne et al, 2002) and in genetic/molecular features in the presence of a multisite metastatic disease (Yokota, 2000) may explain variable results in these pharmacogenetic studies.…”

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confidence: 99%

Liver-only metastatic colorectal cancer patients and thymidylate synthase polymorphisms for predicting response to 5-fluorouracil-based chemotherapy

et al. 2008

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We investigated the association between thymidylate synthase (TS) germline polymorphisms and response to 5-fluorouracil-based chemotherapy in 80 patients with liver-only metastatic colorectal cancer (MCRC). The tandem repeat polymorphism (VNTR) in TS 5 0 -untranslated region (5 0 -UTR), which consists of two (2R) or three (3R) 28-bp repeated sequences, with or without a G/C nucleotide change in 3R carriers (3G or 3C) and a 6-bp insertion/deletion (6 þ /6À) in the TS 3 0 -UTR, was studied. The distinction between high (2R/3G, 3C/3G and 3G/3G) and low (2R/2R, 2R/3C and 3C/3C) TS expression genotypes according to the 5 0 -UTR VNTR þ G/C nucleotide change showed significant association with tumour response (P ¼ 0.01). In particular, high TS expression genotypes were found in 8 out of 34 patients (23.5%) with complete or partial response and in 24 out of 46 patients (52%) with stable disease and disease progression. Liver-only MCRC patients are a homogeneous and clinical relevant subgroup that may represent an ideal setting for studying the actual influence of TS polymorphisms.

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“…In the largest series, a multivariate analysis of 3825 patients treated with FU-based chemotherapy, performance status, the number of metastatic sites, alkaline phosphatase, and the leukocyte count were identified as the most relevant parameters (Köhne et al, 2002).…”

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confidence: 99%

Side effects during chemotherapy predict tumour response in advanced colorectal cancer

et al. 2005

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To investigate whether a relationship between chemotherapy-associated adverse events and treatment efficacy exists, we have analysed the toxicity, objective response and survival data of 303 patients with advanced colorectal cancer. Patients were divided into two groups: the first with beneficial effect (I, n ¼ 245), and the second with progressive disease (II, n ¼ 58). Differences in terms of incidence rates, type and severity of adverse events were analysed with univariate and multivariate models. The median number of side effects in group I was 6 vs 4 in group II (OR ¼ 1.342; P ¼ 0.0001). An inverse correlation between disease control and treatment tolerance was confirmed when side effects were analysed according to severity and type of treatment-associated toxicities (haematological: P ¼ 0.0005 vs nonhaematological P ¼ 0.0001). When median survival was analysed according to the number of adverse events, it was 10 (95% CI, 3 -7), 16 (14 -18), and 18 (16 -20) months in case of 0 -1, 2 -5, and X6 adverse events, respectively (P ¼ 0.01). In conclusion, the results of this analysis suggest that occurrence of side effects during chemotherapy in advanced colorectal cancer is an independent and reliable prognostic indicator for response and survival.

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Clinical determinants of survival in patients with 5-fluorouracil- based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients

Cited by 433 publications

References 38 publications

Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases

Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases

Liver-only metastatic colorectal cancer patients and thymidylate synthase polymorphisms for predicting response to 5-fluorouracil-based chemotherapy

Side effects during chemotherapy predict tumour response in advanced colorectal cancer

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