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Administration of adjuvant chemotherapy for stage II-III colon cancer patients: An European population-based study.

ABSTRACT: The advantage of adjuvant chemotherapy (ACT) for treating Stage III colon cancer patients is well established and widely accepted. However, many patients with Stage III colon cancer do not receive ACT. Moreover, there are controversies around the effectiveness of ACT for Stage II patients. We investigated the administration of ACT and its association with overall survival in resected Stage II (overall and stratified by low-/high-risk) and Stage III colon cancer patients in three European countries including The Netherlands (2009-2014), Belgium (2009-2013) and Sweden (2009-2014). Hazard ratios (HR) for death were obtained by Cox regression models adjusted for potential confounders. A total of 60244 resected colon cancer patients with pathological Stages II and III were analyzed. A small proportion (range 9-24%) of Stage II and over half (range 55-68%) of Stage III patients received ACT. Administration of ACT in Stages II and III tumors decreased with higher age of patients. Administration of ACT was significantly associated with higher overall survival in high-risk Stage II patients (in The Netherlands (HR; 95%CI?=?0.82 (0.67-0.99), Belgium (0.73; 0.59-0.90) and Sweden (0.58; 0.44-0.75)), and in Stage III patients (in The Netherlands (0.47; 0.43-0.50), Belgium (0.46; 0.41-0.50) and Sweden (0.48; 0.43-0.54)). In Stage III, results were consistent across subgroups including elderly patients. Our results show an association of ACT with higher survival among Stage III and high-risk Stage II colon cancer patients. Further investigations are needed on the selection criteria of Stages II and III colon cancer patients for ACT.

SUBMITTER: Babaei M

PROVIDER: S-EPMC6002808 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Administration of adjuvant chemotherapy for stage II-III colon cancer patients: An European population-based study.

Babaei Masoud M Balavarca Yesilda Y Jansen Lina L Lemmens Valery V van Erning Felice N FN van Eycken Liesbet L Vaes Evelien E Sjövall Annika A Glimelius Bengt B Ulrich Cornelia M CM Schrotz-King Petra P Brenner Hermann H

International journal of cancer 20171204 7

The advantage of adjuvant chemotherapy (ACT) for treating Stage III colon cancer patients is well established and widely accepted. However, many patients with Stage III colon cancer do not receive ACT. Moreover, there are controversies around the effectiveness of ACT for Stage II patients. We investigated the administration of ACT and its association with overall survival in resected Stage II (overall and stratified by low-/high-risk) and Stage III colon cancer patients in three European countri ...[more]

PMID: 29159866

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Project description:BackgroundSince 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures.MethodsWe performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12.ResultsAfter 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority).ConclusionsAmong patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.).

Project description:BackgroundAmong patients with resected colon cancer, black patients have worse survival than whites. We investigated whether disparities in survival and related endpoints would persist when patients were treated with identical therapies in controlled clinical trials.MethodsWe assessed 14,611 patients (1218 black and 13,393 white) who received standardized adjuvant treatment in 12 randomized controlled clinical trials conducted in North America for resected stage II and stage III colon cancer between 1977 and 2002. Individual patient data on covariates and outcomes were extracted from the Adjuvant Colon Cancer ENdpoinTs (ACCENT) database. The endpoints examined in this meta-analysis were overall survival (time to death), recurrence-free survival (time to recurrence or death), and recurrence-free interval (time to recurrence). Cox models were stratified by study and controlled for sex, stage, age, and treatment to determine the effect of race. Kaplan-Meier estimates were adjusted for similar covariates to control for confounding. All statistical tests were two-sided.ResultsBlack patients were younger than whites (median age, 58 vs 61 years, respectively; P < .001) and more likely to be female (55% vs 45%, respectively; P < .001). Overall survival was worse in black patients than whites (hazard ratio [HR] of death = 1.22, 95% confidence interval [CI] = 1.11 to 1.34, P < .001). Five-year overall survival rates for blacks and whites were 68.2% and 72.8%, respectively. When subsets defined by sex, stage, and age were analyzed, overall survival was consistently worse in black patients. Recurrence-free survival was worse in black patients than whites (HR of recurrence or death = 1.14, 95% CI = 1.04 to 1.24, P = .0045). Three-year recurrence-free survival rates in blacks and whites were 68.4% and 72.1%, respectively. In contrast, recurrence-free interval was similar in black and white patients (HR of recurrence = 1.08, 95% CI = 0.97 to 1.19, P = .15). Three-year recurrence-free interval rates in blacks and whites were 71.3% and 74.2%, respectively.ConclusionsBlack patients with resected stage II and stage III colon cancer who were treated with the same therapy as white patients experienced worse overall and recurrence-free survival, but similar recurrence-free interval, compared with white patients. The differences in survival may be mostly because of factors unrelated to the patients' adjuvant colon cancer treatment.

Project description:BackgroundChemotherapy is an established treatment for stage III colon cancer cases. Older age is known to be associated with less chemotherapy use in these patients, but there might be other relevant factors besides age that influence treatment administration. We summarized evidence on associations between comorbidity and adjuvant chemotherapy administration in stage III colon cancer patients in a systematic review and meta-analysis.MethodsWe searched the PubMed and Web of Science databases up to 2 June 2020 for studies on comorbidities and chemotherapy use in patients with stage III colon cancer. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using random-effects models. Subgroup analyses according to year of colon cancer diagnosis, timing of comorbidity assessment, and geographical region were also conducted.ResultsThirty-three studies were included in this review, including 219,406 stage III colon cancer patients overall. Chemotherapy administration was 60.9% (95% CI: 56.9% to 64.9%), increasing from 57.1% before 2001 to 66.3% after 2010. There were inverse associations between comorbidities and chemotherapy administration. Compared with patients with Charlson comorbidity score 0, those with scores 1 (OR = 0.79, 95% CI = 0.72-0.87) and 2+ (OR = 0.49, 95% CI = 0.42-0.56) received chemotherapy less often. Among comorbidities, the strongest predictors of chemotherapy non-use were dementia (OR = 0.37, 95% CI = 0.33-0.54), followed by heart failure (OR = 0.44, 95% CI = 0.28-0.70) and stroke (OR = 0.56, 95% CI = 0.38-0.81).ConclusionsMerely 60% of stage III colon cancer patients receive chemotherapy. Comorbidities are strong predictors of chemotherapy non-use, but the association differs by comorbid condition and is strongest with dementia. Given the survival disadvantage of colon cancer patients with comorbidities, further evidence on the risk-benefit ratio of chemotherapy according to the type and severity of comorbidity and on the extent to which the survival disadvantage of comorbidity is explained by less use or lower tolerability of chemotherapy is needed to foster personalized medical care in these patients.

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Administration of adjuvant chemotherapy for stage II-III colon cancer patients: An European population-based study.

Publications

Administration of adjuvant chemotherapy for stage II-III colon cancer patients: An European population-based study.

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