Efficacy of Oral Adjuvant Therapy After Resection of Colorectal Cancer: 5-Year Results From Three Randomized Trials

2004 ◽  
Vol 22 (3) ◽  
pp. 484-492 ◽  
Author(s):  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Therapy ◽  
Oral Therapy ◽  
Randomized Trials ◽  
Early Stage ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Oral Fluoropyrimidines ◽  
Disease Free

Purpose Adjuvant therapy of colorectal cancer with oral fluorinated pyrimidines is attractive because of its ease of administration and good tolerability. The purpose of this meta-analysis is to assess the survival and disease-free survival benefits of treating patients after surgical resection of a primary colorectal tumor with oral fluoropyrimidines for 1 year. Patients and Methods This meta-analysis was performed on individual data from three randomized trials conducted by the Japanese Foundation for Multidisciplinary Treatment for Cancer involving a total of 5,233 patients with stages I to III colorectal cancer. Results The overall hazard ratio in favor of oral therapy was 0.89 for survival (95% CI, 0.80 to 0.99; P = .04), and 0.85 for disease-free survival (95% CI, 0.77 to 0.93; P < .001). Thus oral therapy reduced the risk of death by 11% and the risk of recurrence or death by 15%. There was no significant heterogeneity between trials, nor did the benefit of oral therapy depend on tumor stage (I, II, or III), tumor site (rectum or colon), patient age, or patient sex. Conclusion Oral fluoropyrimidines improve disease-free survival and survival of patients after resection of early-stage colorectal cancer. These observations support the use of these agents alone after resection of early-stage disease, as well as further testing of oral agents in combination with new drugs that have recently shown antitumor activity in advanced colorectal cancer.

Adjuvant chemotherapy in colorectal cancer with high-dose leucovorin and fluorouracil: impact on disease-free survival and overall survival.

1997 ◽  
Vol 15 (6) ◽  
pp. 2432-2441 ◽  
Author(s):  
A Zaniboni
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Randomized Trials ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
Disease Free

PURPOSE The rationale for using adjuvant chemotherapy in colorectal cancer is to achieve better disease control and thus reduce the high rates of tumor recurrence and mortality in patients who undergo curative surgery. The current literature, including relevant abstracts, on clinical trials of fluorouracil (5-FU) in combination with high-dose leucovorin as adjuvant chemotherapy for colorectal cancer is reviewed. The intent is not to present new data, but to present the reader with a broad perspective and larger patient experience on which to base well-reasoned treatment decisions. DESIGN Published clinical trials and abstracts presented at the 1996 American Society of Clinical Oncology (ASCO) meeting that assessed 5-FU in combination with high-dose leucovorin as adjuvant chemotherapy for colorectal cancer were surveyed. End points of interest were disease-free survival (DFS), overall survival, and toxicity. RESULTS In randomized trials that used high-dose leucovorin at doses that ranged from daily-times-five 200 mg/m2 to weekly 500 mg/m2 in combination with 5-FU, significant improvements in both DFS and overall survival were observed over surgery alone (control). In patients treated with high-dose leucovorin/5-FU, DFS rates ranged from 71% to 77% compared with control (58% to 64%). A similar trend was seen in overall survival, with a range of 75% to 84% compared with control (63% to 77%). Toxicities observed for high-dose leucovorin administered on a weekly or daily-times-five schedule were diarrhea, stomatitis, myelosuppression, and nausea. CONCLUSION Overall, the results of these randomized trials support the use of high-dose leucovorin/5-FU as adjuvant therapy for colorectal cancer. Longer follow-up studies are needed to compare the benefits of these different regimens in terms of survival and to characterize adverse effects, especially those that may not be immediately evident. Adjuvant therapy with high-dose leucovorin/5-FU is an effective regimen that is well tolerated by many patients with colorectal cancer.

Adjuvant Therapy for Stage II Colon Cancer: A Systematic Review From the Cancer Care Ontario Program in Evidence-Based Care’s Gastrointestinal Cancer Disease Site Group

2004 ◽  
Vol 22 (16) ◽  
pp. 3395-3407 ◽  
Author(s):  
Alvaro Figueredo ◽  
Manya L. Charette ◽  
Jean Maroun ◽  
Melissa C. Brouwers ◽  
Lisa Zuraw
Keyword(s):  
Systematic Review ◽  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Therapy ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free

Purpose To develop a systematic review that would address the following question: Should patients with stage II colon cancer receive adjuvant therapy? Methods A systematic review was undertaken to locate randomized controlled trials comparing adjuvant therapy to observation. Results Thirty-seven trials and 11 meta-analyses were included. The evidence for stage II colon cancer comes primarily from a trial of fluorouracil plus levamisole and a meta-analysis of 1,016 patients comparing fluorouracil plus folinic acid versus observation. Neither detected an improvement in disease-free or overall survival for adjuvant therapy. A recent pooled analysis of data from seven trials observed a benefit for adjuvant therapy in a multivariate analysis for both disease-free and overall survival. The disease-free survival benefits appeared to extend to stage II patients; however, no P values were provided. A meta-analysis of chemotherapy by portal vein infusion has also shown a benefit in disease-free and overall survival for stage II patients. A meta-analysis was conducted using data on stage II patients where data were available (n = 4,187). The mortality risk ratio was 0.87 (95% CI, 0.75 to 1.01; P = .07). Conclusion There is preliminary evidence indicating that adjuvant therapy is associated with a disease-free survival benefit for patients with stage II colon cancer. These benefits are small and not necessarily associated with improved overall survival. Patients should be made aware of these results and encouraged to participate in active clinical trials. Additional investigation of newer therapies and more mature data from the presently available trials should be pursued.

scholarly journals Allogeneic Peripheral Blood Stem-Cell Compared With Bone Marrow Transplantation in the Management of Hematologic Malignancies: An Individual Patient Data Meta-Analysis of Nine Randomized Trials

2005 ◽  
Vol 23 (22) ◽  
pp. 5074-5087 ◽  
Keyword(s):  
Late Stage ◽  
Randomized Trials ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Free Survival ◽  
Stage Disease ◽  
Disease Free

Purpose Considerable uncertainty exists regarding relative effects of allogeneic peripheral blood stem cells transplantation (PBSCT) versus bone marrow transplantation (BMT) on outcomes of patients with hematologic malignancies. Patients and Methods To provide the totality of research evidence related to the effects of PBSCT versus BMT, we conducted an individual-patient data meta-analysis using data from nine randomized trials enrolling 1,111 adult patients. Results Compared with BMT, PBSCT led to faster neutrophil (odds ratio [OR] = 0.31; 95% CI, 0.25 to 0.38; P < .00001) and platelet engraftment (OR = 0.52; 95% CI, 0.44 to 0.61; P < .00001). PBSCT was associated with a significant increase in the development of grade 3-4 acute graft-versus-host disease (GVHD; OR = 1.39; 95% CI, 1.03 to 1.88) and extensive (47% v 31% at 3 years; OR = 1.89; 95% CI, 1.47 to 2.42; P < .000001) and overall chronic GVHD (68% v 52% at 3 years; OR = 1.92; 95% CI, 1.47 to 2.49; P < .000001), but not grade 2-4 acute GVHD (54% v 53%; P = .49). PBSCT was associated with a decrease in relapse (21% v 27% at 3 years; OR = 0.71; 95% CI, 0.54 to 0.93; P = .01) in both late-stage–(33% v 51% at 3 years; OR = 0.59; 95% CI, 0.38 to 0.93; P = .02) and early-stage–disease patients (16% v 20% at 3 years; OR = 0.69; 95% CI, 0.49 to 0.98; P = .04). Nonrelapse mortality was not different between groups. Overall and disease-free survival were only statistically significantly improved in patients with late-stage disease (overall survival: 46% v 31% at 3 years; OR = 0.64; 95% CI, 0.46 to 0.90; P = .01; disease-free survival: 41% v 27% at 3 years; OR = 0.63 95% CI, 0.45 to 0.87; P = .01). Conclusion PBSCT is associated with a decreased relapse rate in hematologic malignancies and improvement in overall and disease-free survival in patients with late-stage disease. PBSCT is also associated with a significant risk of extensive chronic GVHD.

scholarly journals Prognostic value of the C-reactive protein to albumin ratio in colorectal cancer: an updated systematic review and meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Kai Liao ◽  
Yen-Lin Yu ◽  
Yueh-Chen Lin ◽  
Yu-Jen Hsu ◽  
Yih-Jong Chern ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Pre Treatment ◽  
Disease Free

Abstract Backgrounds The inflammatory biomarker “C-reactive protein to albumin ratio (CAR)” has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. Methods We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. Results A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808−2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321–2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. Conclusions High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.

Immune-related gene signature in predicting prognosis of early-stage colorectal cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3586-3586
Author(s):  
Jia Ke ◽  
Xuanhui Liu ◽  
Xiaofeng Jiang ◽  
Yufeng Chen ◽  
Zerong Cai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Disease Free Survival ◽  
Gene Signature ◽  
Free Survival ◽  
Training Cohort ◽  
Immune Related Genes ◽  
Colorectal Cancer Patients ◽  
Disease Free

3586 Background: Immune-related genes (IRGs) were found to be associated with the prognosis of colorectal cancer (CRC) patients. The aim of this study was to evaluate the impact of IRGs in predicting prognosis of early-stage CRC patients. Methods: According to the CIT microarray data set, 309 early-stage CRC patients were selected for generation of immune-related gene signature (IRGS). 5 independent data sets included 1587 CRC patients with complete prognostic information were divided into a training cohort (566 patients) and two validation cohorts (624 patients in validation-1 and 397 patients in meta-validation). Prognostic analysis were performed to test the predictive value of IRGS. Results: Of 309 early-stage CRC patients, a prognostic immune signature included 23 immune-related genes was constructed. In the training cohort, when considering patients with early tumor stage (I or II), IRGS significantly stratified patients into immune low- vs high-risk groups in terms of disease-free survival (HR = 5.03, 95%CI = 2.94-8.62, P < 0.001). Similarly, higher IRGS was correlated with significantly worse prognosis of early-stage CRC patients in validation-1 (HR = 2.71, 95%CI = 1.44-5.08, P = 0.001) and meta-validation cohort (HR = 3.10, 95%CI = 1.60-6.00, P < 0.001). When compared with Oncotype DX, we found IRGS achieved an improved survival correlation in the training cohort (mean C-index, 0.85 vs 0.65) and the validation-1 cohort (mean C-index, 0.72 vs 0.61). After integrated with clinical characteristics, IRGS remained as an independent prognostic factor after adjusting for T stage and TNM stage of tumor in multivariate analysis (HR = 2.02, 95%CI = 1.61-2.53, P < 0.001). Furthermore, IRGS stratified immune low-risk group patients with adjuvant chemotherapy showed even worse disease-free survival when compared with those without adjuvant chemotherapy (HR = 5.66, 95%CI = 3.153-10.16, P < 0.001 in the training cohort and HR = 3.21, 95%CI = 1.74-5.92, P < 0.001 in the validation-1 cohort). IRGS identified immune high-risk group obtained a significantly higher immune and stromal infiltration (P < 0.001). Particularly, the percentages of Macrophages M2 and CD8+ T cells infiltration were significantly different between these two groups. Conclusions: The proposed prognostic IRGS is a promising system for estimating DFS of colorectal cancer patients, especially those in early-stage. Further studies are needed to evaluate the clinical utility of this system in predicting prognosis of colorectal cancer patients.

scholarly journals Biomarker roles identification of miR-106 family for predicting the risk and poor survival of colorectal cancer

2020 ◽  
Author(s):  
Qiliang Peng ◽  
Yi Shen ◽  
Peifeng Zhao ◽  
Ming Cheng ◽  
Yaqun Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanism ◽  
Bioinformatics Analysis ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Poor Survival ◽  
Free Survival ◽  
Diagnosis And Prognosis ◽  
Disease Free ◽  
Normal Controls

Abstract Background: Recent studies have extensively investigated the roles of miR-106 in colorectal cancer (CRC). However, the associations and molecular mechanism underlying the roles of miR-106 in CRC remain unclear. We aimed to thoroughly investigate the biomarker roles of miR-106 for predicting the risk and survival outcome in CRC.Methods: We first conducted a comprehensive meta-analysis to quantitatively evaluate the roles of miR-106 in the diagnosis and prognosis of CRC. Then, we qualitatively explored the biomarker roles of miR-106 in CRC through an integrative bioinformatics analysis. Results: The results indicated that miR-106 yielded a combined AUC of 0.79 (95% CI: 0.76–0.83), with a pooled sensitivity of 0.50 (95% CI: 0.32–0.68) and a pooled specificity of 0.93 (95% CI: 0.79–0.98) for discriminating CRC cases from normal controls. Moreover, patients with higher expression of miR-106 were significantly associated with shorter disease-free survival (HR: 1.73; 95%CI: 1.23-2.44) and overall survival (HR: 1.39; 95%CI: 1.09-1.77). Finally, gene ontology and pathway analysis demonstrated that miR-106 family was highly involved in the initiation and progression of CRC and indicated the potential molecular mechanism for miR-106 in CRC.Conclusions: Our results indicated that miR-106 showed promising potential as diagnostic and prognostic biomarker for CRC. Nevertheless, the underlying molecular mechanism of miR-106 family involved in CRC requires further investigation.

scholarly journals Liver Transplantation for Non-Resectable Liver Metastases from Colorectal Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Rebecca Varley ◽  
Munir Tarazi ◽  
Madhav Davé ◽  
Shahd Mobarak ◽  
Martyn C. Stott ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Transplantation ◽  
Liver Metastases ◽  
Colorectal Liver Metastases ◽  
Palliative Chemotherapy ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Current Evidence ◽  
Free Survival ◽  
Disease Free

Abstract Backgrounds Colorectal liver metastases were historically considered a contraindication to liver transplantation, but dismal outcomes for those with metastatic colorectal cancer and advancements in liver transplantation (LT) have led to a renewed interest in the topic. We aim to compare the current evidence for liver transplantation for non-resectable colorectal liver metastases (NRCLM) with the current standard treatment of palliative chemotherapy. Methods A systematic review and meta-analysis of proportions was conducted following screening of MEDLINE, EMBASE, SCOPUS and CENTRAL for studies reporting liver transplantation for colorectal liver metastases. Post-operative outcomes measured included one-, three- and five-year survival, overall survival, disease-free survival and complication rate. Results Three non-randomised studies met the inclusion criteria, reporting a total of 48 patients receiving LT for NRCLM. Survival at one-, three- and five-years was 83.3–100%, 58.3–80% and 50–80%, respectively, with no significant difference detected (p = 0.22, p = 0.48, p = 0.26). Disease-free survival was 35–56% with the most common site of recurrence being lung. Thirteen out of fourteen deaths were due to disease recurrence. Conclusion Although current evidence suggests a survival benefit conferred by LT in NRCLM compared to palliative chemotherapy, the ethical implications of organ availability and allocation demand rigorous justification. Concomitant improvements in the management of patients following liver resection and of palliative chemotherapy regimens is paramount.

Sign in / Sign up

Export Citation Format

Share Document