Prevalent diabetes and risk of total,colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Background We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.Methods We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.Results A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I² = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I² = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I² = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I² = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I² = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.Conclusions Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.Subject terms: Risk factors, Cancer epidemiology     

Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis

BackgroundChemotherapy (CT) combined with radiotherapy is the standard treatment of ‘limited-stage’ small-cell lung cancer. However, controversy persists over the optimal timing of thoracic radiotherapy and CT.Materials and methodsWe carried out a meta-analysis of individual patient data in randomized trials comparing earlier versus later radiotherapy, or shorter versus longer radiotherapy duration, as defined in each trial. We combined the results from trials using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival.ResultsTwelve trials with 2668 patients were eligible. Data from nine trials comprising 2305 patients were available for analysis. The median follow-up was 10 years. When all trials were analysed together, ‘earlier or shorter’ versus ‘later or longer’ thoracic radiotherapy did not affect overall survival. However, the HR for overall survival was significantly in favour of ‘earlier or shorter’ radiotherapy among trials with a similar proportion of patients who were compliant with CT (defined as having received 100% or more of the planned CT cycles) in both arms (HR 0.79, 95% CI 0.69–0.91), and in favour of ‘later or longer’ radiotherapy among trials with different rates of CT compliance (HR 1.19, 1.05–1.34, interaction test, P < 0.0001). The absolute gain between ‘earlier or shorter’ versus ‘later or longer’ thoracic radiotherapy in 5-year overall survival for similar and for different CT compliance trials was 7.7% (95% CI 2.6–12.8%) and -2.2% (-5.8% to 1.4%), respectively. However, ‘earlier or shorter’ thoracic radiotherapy was associated with a higher incidence of severe acute oesophagitis than ‘later or longer’ radiotherapy.Conclusion‘Earlier or shorter’ delivery of thoracic radiotherapy with planned CT significantly improves 5-year overall survival at the expense of more acute toxicity, especially oesophagitis.     

Impact of EGFR expression on colorectal cancer patient prognosis and survival.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviors. The aim of this study was to evaluate EGFR immunohistochemical reactivity in CRC biopsies, and to analyze its relationship with various histological and clinical characteristics and survival. PATIENTS AND METHODS: A composite EGFR score, obtained by multiplying the grade (% positive cells) by the intensity of labeling (0-9) was used to define patients with low or high EGFR expression whose clinicopathological features were then compared. Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. RESULTS: Tissue sections from 150 CRC patients with a median follow-up of 40 months were examined. Median patient age at diagnosis was 70 years (range 38-89 years). EGFR reactivity was positive for 143 patients (97%) and high for 118 (80%). According to multivariate analysis, EGFR overexpression was significantly associated with tumor stage, with a higher percentage of EGFR overexpression in T3 than T4 (P=0.003) and not with overall survival. CONCLUSIONS: EGFR was overexpressed in this CRC patient population and was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.     

Meningiomas in children and adolescents: a meta-analysis of individual patient data

Background

The epidemiological, prognostic, and therapeutic features of child and adolescent meningioma are poorly defined. Clinical knowledge has been drawn from small case series and extrapolation from adult studies. This study was done to pool and analyse the clinical evidence on child and adolescent meningioma.

Methods

Searches of PubMed, Medline, and Embase identified 35 case series of child and adolescent meningioma completed over the past 21 years. Individual patient data were obtained from 30 studies via direct communication with investigators. Primary outcomes were relapse-free survival (RFS) and overall survival. Prognostic variables were extent of initial surgery, use of upfront radiotherapy, age, sex, presence of neurofibromatosis, tumour location, and tumour grade. RFS and overall survival were analysed using Kaplan-Meier survival curves and multivariable Cox regression models.

Findings

From a total of 677 children and adolescents with meningioma, 518 were eligible for RFS analysis and 547 for overall survival analysis. Multivariable analysis showed that patients who underwent initial gross-total resection had better RFS (hazard ratio 0·16, 95% CI 0·10–0·25; p<0·0001) and overall survival (0·21, 0·11–0·39; p<0·0001) than those who had subtotal resection. No significant benefit was seen for upfront radiotherapy in terms of RFS (0·59, 0·30–1·16; p=0·128) or overall survival (1·10, 0·53–2·28; p=0·791). Patients with neurofibromatosis type 2 (NF2) had worse RFS than those without neurofibromatosis (2·36, 1·23–4·51; p=0·010). There was a significant change in overall survival with time between patients with NF2 compared with those without neurofibromatosis (1·45, 1·09–1·92; p=0·011); although overall survival was initially better for patients with NF2 than for those without neurofibromatosis, overall survival at 10 years was worse for patients with NF2. Patients with WHO grade III tumours had worse RFS than those with WHO grade I (3·90, 2·10–7·26; p<0·0001) and grade II tumours (2·49, 1·11–5·56; p=0·027).

Interpretation

Extent of initial surgical resection is the strongest independent prognostic factor for child and adolescent meningioma. No benefit for upfront radiotherapy was noted. Hence, aggressive surgical management, to achieve gross-total resection, is the initial treatment of choice. In the event of a subtotal resection, repeat resection is recommended to achieve maximum extirpation. Close observation is warranted for patients who have a subtotal resection or who have WHO grade III tumours. Patients without neurofibromatosis should have a minimum 10-year follow-up, whereas patients with NF2 should be considered a special risk category, necessitating life-long follow-up.

Funding

None.     

Matrix metalloproteinase 9 expression and prognosis in colorectal cancer: a meta-analysis

Matrix metalloproteinase-9 (MMP-9) is an important member of the matrix metalloproteinase family and is considered to be involved in the invasion and metastasis of cancer cells. Many studies were published to assess the prognostic role of MMP-9 overexpression in patients with colorectal cancer, but the findings from those studies were inconsistent. We searched eligible studies in Pubmed, Embase, and Web of Science databases. Thirteen studies with a total of 2, 390 CRC patients were finally included into the meta-analysis. The pooled hazard ratios (HRs) with the corresponding 95 % confidence interval (95 % CIs) for overall and progression-free survival were calculated by using meta-analysis. There were nine studies with a total of 1,674 colorectal cancer patients relating the progression-free survival, and eight studies with a total of 1,379 colorectal cancer patients relating the overall survival. Overall, MMP-9 overexpression was associated with poorer progression-free survival in patients with colorectal cancer (fixed-effects HR 1.81, 95 % CI 1.48–2.20, P?<?0.001; random-effects HR 1.92, 95 % CI 1.46–2.53, P?<?0.001). In addition, MMP-9 overexpression was also associated with poorer overall survival in patients with colorectal cancer (fixed-effects HR 1.74, 95 % CI 1.39–2.19, P?<?0.001; random-effects HR 1.78, 95 % CI 1.31–2.41, P?<?0.001). MMP-9 expression is associated with the prognosis of patients with colorectal cancer, and patients with higher MMP-9 expression have poorer survival.     

Postoperative radiotherapy in non-small-cell lung cancer: update of an individual patient data meta-analysis

We report an updated systematic review and individual patient data meta-analysis of the effectiveness of postoperative radiotherapy (PORT) in non-small-cell lung cancer. Results continue to show PORT to be detrimental, with an 18% relative increase in the risk of death. Similar detriments were observed for local recurrence-free survival, distant recurrence-free survival and overall recurrence-free survival. There continues to be evidence that the effects of PORT are more harmful in those patients with stage I disease than those with stage II disease.     

Chemotherapy-induced neutropenia and the prognosis of colorectal cancer: a meta-analysis of cohort studies

Introduction: Recently, there has been a controversial discussion about the prognostic value of chemotherapy-induced neutropenia (CIN) in colorectal cancer patients. Thus, a meta-analysis was conducted to determine the relationship between CIN and the prognosis of colorectal cancer patients.

Methods: We searched the PubMed, EMBASE, and Cochrane library databases to identify studies evaluating the association between CIN and colorectal cancer prognosis. Pooled random/fixed effect models were used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association.

Results: Eight studies were selected for the meta-analysis, for a total of 2,745 patients. There was significant improved survival among colorectal cancer patients with CIN (HR = 0.62, 95% CI = 0.47–0.76). However, significant heterogeneity was found (p = 0.000, Ι² = 75.0%). Through subgroup analysis, we could greatly eliminate the heterogeneity and found that neutropenia was associated with better survival in stage IV colorectal cancer patients, no matter the HR calculated by overall survival (OS) or progression-free survival (PFS). Meanwhile, the prognostic value of neutropenia in stage II/III colorectal cancer can be found when the HR is calculated by disease-free survival (DFS). Additionally, we observed significant differences after stratification according to various tumor stages, endpoints, and the use of G-CSF.

Conclusions: Our results which, based on a cohort study, indicate that CIN is associated with improved survival in patients with colorectal cancer. However, further randomized controlled trials are warranted.     

Platinum versus platinum-combination chemotherapy in platinum-sensitive recurrent ovarian cancer: a meta-analysis using individual patient data

BackgroundThe majority of women with ovarian cancer develop recurrent disease. For patients with a platinum-free interval of >6 months, platinum-based chemotherapy is a treatment of choice. The benefit of platinum-based combination chemotherapy in randomized trials varies, and a meta-analysis was carried out to gain more secure information on the size of the benefit of this treatment.Materials and methodsWe initiated a systematic review and meta-analysis following a pre-specified protocol to determine whether combination chemotherapy is superior to single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer.ResultsA total of five potentially eligible randomized trials were identified that had used combination-platinum chemotherapy versus single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer. For one trial (190 patients), adequate contact with the investigators could not be established. Therefore, four trials that randomly assigned 1300 patients were included, with a median follow-up of 36.1 months. Overall survival (OS) analyses were based on 865 deaths and demonstrated evidence for the benefit of combination-platinum chemotherapy (HR = 0.80; 95% CI, 0.64–1.00; P = 0.05). Progression-free survival (PFS) analyses were based on 1167 events and demonstrated strong evidence for the benefit of combination-platinum chemotherapy (HR = 0.68; 95% CI, 0.57–0.81; P < 0.001). There was no evidence of a difference in the relative effect of combination-platinum chemotherapy on either OS or PFS in patient subgroups defined by previous paclitaxel (Taxol) treatment (OS, P = 0.49; PFS, P = 0.66), duration of treatment-free interval (OS, P = 0.86; PFS, P = 0.48) or the number of previous lines of chemotherapy (OS, P = 0.21; PFS, P = 0.27).ConclusionsIn this individual patient data (IPD) meta-analysis, we have demonstrated that combination-platinum chemotherapy improves OS and PFS across all subgroups. This provides the strongest evidence to date of the benefit of combination-platinum over single-agent platinum.     

Neoadjuvant chemotherapy for locally advanced cervical cancer: a systematic review and meta-analysis of individual patient data from 21 randomised trials

Despite the enrollment of more than 3000 women in randomised trials, the benefits and risks of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer remain uncertain. We carried out a systematic review and meta-analysis of individual patient data to assess the effect of neoadjuvant chemotherapy in two comparisons. In the first comparison, of neoadjuvant chemotherapy followed by radical radiotherapy compared with the same radiotherapy alone, we obtained data from 18 trials and 2074 patients. When all trials were considered together, a high level of statistical heterogeneity suggested that the results could not be combined indiscriminately. A substantial amount of heterogeneity was explained by separate analyses of groups of trials. Trials using chemotherapy cycle lengths of 14 days and shorter (Hazard Ratio (HR))=0.83, 95% Confidence Interval (CI)=0.69-1.00, P=0.046) or cisplatin dose intensities greater than or equal to 25 mg/m2 per week (HR=0.91, 95% CI=0.78-1.05, P=0.20) tended to show an advantage for neoadjuvant chemotherapy on survival. In contrast, trials using cycle lengths longer than 14 days (HR=1.25, 95% CI=1.07-1.46, P=0.005) or cisplatin dose intensities lower than 25mg/m2 per week (HR=1.35, 95% CI=1.11-1.14, P=0.002) tended to show a detrimental effect of neoadjuvant chemotherapy on survival. In the second comparison, of neoadjuvant chemotherapy followed by surgery compared with radical radiotherapy alone, data from 5 trials and 872 patients were obtained. The combined results from all trials (HR=0.65, 95% CI=0.53-0.80, P=0.0004) indicated a highly significant reduction in the risk of death with neoadjuvant chemotherapy, but there were some differences between the trials in their design and results. Despite some unexplained heterogeneity, the timing and dose intensity of cisplatin-based neoadjuvant chemotherapy appears to have an important impact on whether or not it benefits women with locally advanced cervical cancer and warrants further exploration.     

Contributions of meta-analyses based on individual patient data to therapeutic progress in colorectal cancer

Meta-analysis is the statistical process of combining information from several studies addressing the same question. Meta-analyses based on individual patient data are far more reliable and informative than those based on summary statistics obtained from the trialists or extracted from the published literature. Meta-analysis of randomized clinical trials may contribute to therapeutic progress through (1) establishing efficacy benefits beyond a reasonable doubt, (2) identifying sources of heterogeneity between trials, (3) studying subsets reliably, (4) confirming differences in toxicity profiles, (5) evaluating the cost-effectiveness of experimental therapies, (6) assessing surrogate endpoints, and (7) addressing ancillary questions. All of these potential contributions are illustrated with examples in early and advanced colorectal cancer.     

Microsatellite instability as a marker of prognosis and response to therapy: A meta-analysis of colorectal cancer survival data

Background and methodsWe have reviewed and pooled data from published studies to evaluate the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Thirty-one eligible studies reporting survival in 12782 patients characterised for MSI were pooled using a fixed- or random-effects model.ResultsThe summary odds ratio (OR) estimate for overall survival (OS) associated with MSI was 0.6 (95%CI 0.53–0.69, p < 0.0001), with no evidence of heterogeneity. The effect was similar for disease-free survival (DFS) (OR = 0.58, 95%CI 0.47–0.72, p < 0.0001). In a subset of patients treated with 5-fluorouracil (5-FU)-based chemotherapy a significant improved prognosis was found for microsatellite stable (MSS) tumours (OR = 0.52, 95%CI 0.4–0.6, p < 0.0001) with no heterogeneity (p = 0.53; I² = 0%). By contrast a large heterogeneity characterised the data relative to 396 patients with MSI tumours (OR = 0.69, 95%CI 0.3–1.5, p = 0.1; heterogeneity: p = 0.03; I² = 58%).ConclusionsThis study confirmed the association between MSI and favourable prognosis as determined by both OS and DFS of CRC patients. A significant beneficial effect of 5-FU therapy was found for MSS tumours whilst no clear conclusion was reached for MSI tumours due to the high inter-study heterogeneity. We propose that this inconclusive result is due to the use of a single marker, such as MSI, that cannot account alone for the complexity of the mechanisms underlying 5-FU cytotoxicity. Future studies to predict response to 5-FU chemotherapy should include additional genome stability markers.     

An individual patient data meta-analysis of long supported adjuvant chemotherapy with oral carmofur in patients with curatively resected colorectal cancer

To reappraise the benefits of the long supported chemotherapy with carmofur, a meta-analysis based on individual patient data from the three clinical trials was performed by pooling 614 patients from three trials, there is a statistically significant survival benefit (2p=0.032) and disease-free survival (DFS) benefit (2p=0.021) for carmofur; and a highly significant advantage for carmofur in DFS (2p=0.0004) and in survival (2p=0.004) in Dukes' C patients. This IPD meta-analysis strongly suggested an effect of oral carmofur in a long supported chemotherapy for curatively resected colorectal carcinoma.     

Tobacco smoking and cancer: a meta-analysis

We conducted a systematic meta-analysis of observational studies on cigarette smoking and cancer from 1961 to 2003. The aim was to quantify the risk for 13 cancer sites, recognized to be related to tobacco smoking by the International Agency for Research on Cancer (IARC), and to analyze the risk variation for each site in a systematic manner. We extracted data from 254 reports published between 1961 and 2003 (177 case-control studies, 75 cohorts and 2 nested case-control studies) included in the 2004 IARC Monograph on Tobacco Smoke and Involuntary Smoking. The analyses were carried out on 216 studies with reported estimates for 'current' and/or 'former' smokers. We performed sensitivity analysis, and looked for publication and other types of bias. Lung (RR = 8.96; 95% CI: 6.73-12.11), laryngeal (RR = 6.98; 95% CI: 3.14-15.52) and pharyngeal (RR = 6.76; 95% CI: 2.86-15.98) cancers presented the highest relative risks (RRs) for current smokers, followed by upper digestive tract (RR = 3.57; 95% CI: 2.63-4.84) and oral (RR = 3.43; 95% CI: 2.37-4.94) cancers. As expected, pooled RRs for respiratory cancers were greater than the pooled estimates for other sites. The analysis of heterogeneity showed that study type, gender and adjustment for confounding factors significantly influence the RRs estimates and the reliability of the studies.     

Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (oesophageal cancer collaborative group)

Purpose: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery.Methods and Materials: This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials.Results: With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78–1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent.Conclusion: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15→20%).     

Adjuvant therapy with oral fluoropyrimidines as main chemotherapeutic agents after curative resection for colorectal cancer: individual patient data meta-analysis of randomized trials

BACKGROUND: Oral 5-fluorouracil and its prodrugs (tegafur, carmofur) is now being studied for adjuvant chemotherapy of curatively resected colorectal cancers. To evaluate the effect of these oral fluoropyrimidines (o-FPs), an individual patient data (IPD) meta-analysis of randomized clinical trials was performed in Japan as an inter-trialist group study. METHODS: Data from the three clinical trials in which postoperative adjuvant therapy with o-FPs was compared with surgery alone in patients with colorectal cancer were sought. IPD from a total of 4960 patients with follow-up periods of at least 5 years were analyzed. RESULTS: The results of the meta-analysis on an 'intention to treat' basis demonstrated a significant benefit of o-FPs in terms of the disease-free survival (DFS) of the total patients [risk ratio (RR) 0.830, 95% confidence interval (CI) 0.742-0.929, P = 0.001]. o-FPs were also demonstrated to be effective for survival in rectal cancer (RR 0.857, 95% CI 0.734-0.999, P = 0.049) and in Dukes'C colorectal cancer (RR 0.828, 95% CI 0.711-0.965, P = 0.016). CONCLUSION: The results suggest the advantage of long term o-FPs, possibly with the injection of mitomycin C, for prognosis for curatively resected colorectal cancer patients.     

Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis

Background:

The role of tumour-infiltrating inflammation in the prognosis of patients with colorectal cancer (CRC) has not been fully evaluated. The primary objective of our meta-analysis was to determine the impact of tumour-infiltrating inflammation on survival outcomes.

Methods:

Ovid MEDLINE and EMBASE were searched to identify studies reporting the prognostic significance of tumour-infiltrating inflammation for patients with CRC. The primary outcome measures were overall survival (OS), cancer-specific survival (CS) and disease-free survival (DFS).

Results:

A total of 30 studies involving 2988 patients were identified. Studies were subdivided into those considering the associations between CRC survival and generalised tumour inflammatory infiltrate (n=12) and T lymphocyte subsets (n=18). Pooled analyses revealed that high generalised tumour inflammatory infiltrate was associated with good OS (HR, 0.59; 95% CI, 0.48–0.72), CS (HR, 0.40; 95% CI, 0.27–0.61) and DFS (HR, 0.72; 95% CI, 0.57–0.91). Stratification by location and T lymphocyte subset indicated that in the tumour centre, CD3⁺, CD8⁺ and FoxP3⁺ infiltrates were not statistically significant prognostic markers for OS or CS. In the tumour stroma, high CD8⁺, but not CD3⁺ or FoxP3⁺ cell infiltrates indicated increased OS. Furthermore, high CD3⁺ cell infiltrate was detected at the invasive tumour margin in patients with good OS and DFS; and high CCR7⁺ infiltrate was also indicated increased OS.

Conclusion:

Overall, high generalised tumour inflammatory infiltrate could be a good prognostic marker for CRC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes to increase the robustness of the analyses.     

Efficacy of capecitabine versus 5-fluorouracil in colorectal and gastric cancers: a meta-analysis of individual data from 6171 patients

BackgroundTo compare the effects of oral capecitabine-containing chemotherapy regimens with i.v. 5-fluorouracil (5-FU)-containing chemotherapy regimens on overall survival in patients with gastrointestinal cancers.MethodsA meta-analysis, based on individual patient data from six randomised non-inferiority trials, was carried out at the request of regulatory authorities to compare the effects of single-agent capecitabine or capecitabine-containing chemotherapy versus matched 5-FU-based regimens in terms of overall survival in patients with stage III colon, metastatic colorectal or advanced gastric cancer.ResultsData from a total of 6171 patients with stage III colon cancer (n = 1987), metastatic colorectal cancer (n = 3868) or advanced gastric cancer (n = 316) were included. A total of 3097 patients were treated with capecitabine-containing chemotherapy and 3074 patients with 5-FU-containing chemotherapy. The unadjusted hazard ratio for overall survival for capecitabine-containing chemotherapy versus 5-FU-containing chemotherapy was 0.94 (95% confidence interval 0.89–1.00; P = 0.0489).ConclusionsOral capecitabine is at least equivalent to i.v. 5-FU in terms of overall survival in patients with gastrointestinal cancers. Capecitabine and 5-FU can be used interchangeably in these patient populations.