Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials

2008 ◽  
Vol 26 (30) ◽  
pp. 4906-4911 ◽  
Author(s):  
Emmanuel Mitry ◽  
Anthony L.A. Fields ◽  
Harry Bleiberg ◽  
Roberto Labianca ◽  
Guillaume Portier ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Complete Resection ◽  
Hazard Ratio ◽  
Free Survival ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

Purpose Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. Patients and Methods After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m2 administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m2 [FFCD] × 5 days or FU 370 mg/m2 plus l-leucovorin 100 mg/m2 IV × 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm). Results A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis. Conclusion This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus–based regimen after complete resection of colorectal cancer metastases.

scholarly journals Colorectal cancer metastases to the lungs: outcomes of surgical treatment and prognostic factors

2020 ◽  
Vol 10 (2) ◽  
pp. 33-41
Author(s):  
B. B. Akhmedov ◽  
P. V. Kononets ◽  
M. Yu. Fedyanin ◽  
Z. Z. Mamedli ◽  
S. S. Gordeev ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Surgical Treatment ◽  
Survival Rate ◽  
Postoperative Complications ◽  
Progression Free Survival ◽  
Free Survival ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

Objective: to evaluate short-term and long-term outcomes of surgical treatment for colorectal cancer metastases to the lungs and to analyze factors affecting the efficacy of surgery. Materials and methods. This study included 211 patients with colorectal cancer metastases to the lungs treated between 1994 and 2014. We enrolled patients with resectable or conventionally resectable metastases (according to chest computed tomography evaluated by a thoracic surgeon); the exclusion criteria were as follows: multiple primary tumors and age more than 85 years. We assessed the type of surgeries, frequency of R0 resections, incidence of postoperative complications, overall survival, and progression-free survival. Results. One hundred and sixty-two patients out of 211 (76.8 %) have undergone atypical lung resection. Forty-nine patients (23.2 %) have undergone pneumonectomy, bilobectomy, or lobectomy. The majority of patients (96.2 %) have had R0 resection, whereas 2.9 % of study participants have had R1 or R2 resections. One patient has undergone a trial surgery. Clinically significant postoperative complications were observed in 4 (2 %) patients; postoperative mortality was 0.5 % (1 case). The five-year overall survival rate was 52.7 %; the 5-year progression-free survival rate was 45.8 %. Development of metastases within 24 months after primary surgery was found to be a significant factor negatively affecting overall survival (hazard ratio 0.347; 95 % confidence interval 0.227–0.53; р <0.0001). Conclusions. Surgical treatment is currently the only truly effective treatment, which can improve long-term survival of patients with colorectal cancer metastases to the lungs; the best treatment results are achieved in patients with a relapse-free interval of more than 24 months. 

Correlation of postoperative CEA trends with survival and patterns of recurrence after hepatectomy for colorectal cancer metastases.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 436-436 ◽  
Author(s):  
Lawrence Andrew Shirley ◽  
Megan McNally ◽  
Justin Huntington ◽  
Natalie Jones ◽  
Lavina Malhotra ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Locoregional Therapy ◽  
Free Survival ◽  
Cancer Metastases ◽  
Significant Difference ◽  
Colorectal Cancer Metastases ◽  
Patterns Of Recurrence

436 Background: Pre-operative carcinoembryonic antigen (CEA) level is associated with outcome after hepatectomy for colorectal cancer metastases. In this study we sought to determine the relationship between post-operative CEA and outcome after hepatectomy. Methods: A single institution retrospective review of hospital records from 1993 to 2010 found 339 patients who underwent a liver resection for CRC metastases. Of these, 140 had CEA levels drawn pre-operatively, post-operatively, and at least once more in follow-up. A ΔCEA level was calculated by subtracting the initial post-operative CEA level from the highest CEA level drawn in follow-up. Outcomes were compared between patients with ΔCEA less than 5 and greater than 5. Results: Of 140 patients, 61 had ΔCEA less than 5 and 79 had ΔCEA greater than 5. Patients with low ΔCEA had improved median overall survival (OS) (70.2 months) compared to those with high ΔCEA (38.7 months, P=0.0001). However, there was no significant difference in progression-free survival (PFS) (13.0 months vs. 12.3 months, P=0.982). 100 patients had recurrence after hepatectomy, 69 with high ΔCEA and 31 with low ΔCEA. Patients with low ΔCEA were more likely to have a single site of recurrence (77.4% vs. 53.6%, P<0.0001). Conclusions: Although a rising CEA after hepatectomy for CRC metastases is associated with worse overall survival, there is no difference in progression-free survival between patients with rising CEA and those with stable-to-decreasing CEA. Patients with stable-to-decreasing CEA have patterns of recurrence more amenable to locoregional therapy. Post-operative CEA values are an important component of oncologic surveillance, and patterns of rise and fall may indicate patterns of recurrence.

scholarly journals Transarterial Radioembolization of Hepatocellular Carcinoma, Liver-Dominant Hepatic Colorectal Cancer Metastases, and Cholangiocarcinoma Using Yttrium90 Microspheres: Eight-Year Single-Center Real-Life Experience

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 122
Author(s):  
Julie Pellegrinelli ◽  
Olivier Chevallier ◽  
Sylvain Manfredi ◽  
Inna Dygai-Cochet ◽  
Claire Tabouret-Viaud ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Progression Free Survival ◽  
Single Center ◽  
Free Survival ◽  
Risk Of Death ◽  
Transarterial Radioembolization ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres® or TheraSphere® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26–0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.

scholarly journals Efficacy and safety of second-line agents for treatment of metastatic castration-resistant prostate cancer progressing after docetaxel. A systematic review and meta-analysis

2015 ◽  
Vol 87 (2) ◽  
pp. 121 ◽  
Author(s):  
Gianpaolo Perletti ◽  
Elena Monti ◽  
Emanuela Marras ◽  
Anne Cleves ◽  
Vittorio Magri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Abiraterone Acetate ◽  
Hazard Ratio ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Androgen Synthesis ◽  
Castration Resistant ◽  
Androgen Synthesis Inhibitors

Objective: We performed a systematic review of the literature to assess the efficacy and the safety of second-line agents targeting metastatic castration-resistant prostate cancer (mCRPC) that has progressed after docetaxel. Pooled-analysis was also performed, to assess the effectiveness of agents targeting the androgen axis via identical mechanisms of action (abiraterone acetate, orteronel). Materials and Methods: We included phase III randomized controlled trials that enrolled patients with mCRPC progressing during or after first-line docetaxel treatment. Trials were identified by electronic database searching. The primary outcome of the review was overall survival. Secondary outcomes were radiographic progression-free survival (rPFS) and severe adverse effects (grade 3 or higher). Results: Ten articles met the inclusion criteria for the review. These articles reported the results of five clinical trials, enrolling in total 5047 patients. The experimental interventions tested in these studies were enzalutamide, ipilimumab, abiraterone acetate, orteronel and cabazitaxel. Compared to control cohorts (active drug-treated or placebotreated), the significant overall survival advantages achieved were 4.8 months for enzalutamide (hazard ratio for death vs. placebo: 0.63; 95% CI 0.53 to 0.75, P &lt; 0.0001), 4.6 months for abiraterone (hazard ratio for death vs. placebo: 0.66, 95% CI 0.58 to 0.75, P &lt; 0.0001) and 2.4 months for cabazitaxel (hazard ratio for death vs. mitoxantrone-prednisone: 0.70, 95% CI 0.59 to 0.83, p &lt; 0.0001). Pooled analysis of androgen synthesis inhibitors orteronel and abiraterone resulted in significantly increased overall and progression-free survival for anti-androgen agents, compared to placebo (hazard ratio for death: 0.76, 95% CI 0.67 to 0.87, P &lt; 0.0001; hazard ratio for radiographic progression: 0.7, 95% CI 0.63 to 0.77, P &lt; 0.00001). Androgen synthesis inhibitors induced significant increases in risk ratios for adverse effects linked to elevated mineralocorticoid secretion, compared to placebo (risk ratio for hypokalemia: 5.75, 95% CI 2.08 to 15.90; P = 0.0008; risk-ratio for hypertension: 2.29, 95% CI 1.02 to 5.17; P = 0.05). Conclusions: In docetaxel-pretreated patients enzalutamide, abiraterone-prednisone and cabazitaxel-prednisone can improve overall survival of patients, compared to placebo or to best of care at the time of study (mitoxantrone-prednisone). Agents targeting the androgen axis (enzalutamide, abiraterone, orteronel) significantly prolonged rPFS, compared to placebo. Further investigation is warranted to evaluate the benefit of combination or sequential administration of these agents. Large-scale studies are also necessary to evaluate the impact of relevant toxic effects observed in a limited number of patients (e.g., enzalutamide-induced seizures, orteronel-induced pancreatitis, and others).

Efficacy and prognostic significance of triflurodine/tipiracil beyond oxaliplatin and irinotecan based chemotherapy in patients with refractory metastatic colorectal cancer: An observational multicenter study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15586-e15586
Author(s):  
Mohamed Alghamdi ◽  
Shouki Bazarbashi ◽  
Elsamany Shereef ◽  
Mervat Mahrous ◽  
Omar Al shaer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Saudi Arabia ◽  
Neutrophil Count ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
P Value ◽  
Second Line ◽  
First Line ◽  
Free Survival

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.

scholarly journals Effects of Antihypertensive Drugs Use on Risk and Prognosis of Colorectal Cancer: A Meta-Analysis of 37 Observational Studies

2022 ◽  
Vol 12 ◽  
Author(s):  
Yujiao Deng ◽  
Yuxiu Xie ◽  
Meng Wang ◽  
Peng Xu ◽  
Bajin Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Enzyme Inhibitors ◽  
Antihypertensive Drugs ◽  
Progression Free Survival ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Free Survival ◽  
Receptor Blockers

Background: Antihypertensive drugs might play a key role in the risk and poor prognosis of colorectal cancer. However, current epidemiologic evidence remains inconsistent. The aim of this study is to quantify the association between antihypertensive drugs and colorectal cancer.Methods: To identify available studies, we systematically searched electronic databases: PubMed, Web of Science, Embase, Cochrane Library. The risk estimates and their corresponding 95% confidence intervals (CIs) were collected and analyzed by using random-effects models. Heterogeneity test and sensitivity analysis were also performed.Results: Overall, 37 observational studies were included in this analysis (26 studies with cohort design, three studies with nested case-control design, and 8 studies with case-control design). Antihypertensive drugs did not present a significant effect on the risk or overall survival of patients with colorectal cancer [Risk ratio (RR) = 1.00, 95% CI: 0.95–1.04; Hazard ratio (HR) = 0.93, 95% CI: 0.84–1.02]. In the subgroup analysis, diuretics use was significantly associated with a worse overall survival of patients with colorectal cancer (HR = 1.27; 95% CI: 1.14–1.40). However, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was associated with improved progression-free survival of patients who suffered from colorectal cancer (HR = 0.83; 95% CI: 0.72–0.95).Conclusion: Antihypertensive drug usage did not influence the risk and overall survival of patients with colorectal cancer in general. Further investigation reminded us that diuretics use might reduce the overall survival time in colorectal cancer patients, whereas those who took Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers had a longer progression-free survival.

scholarly journals Local ablation or radioembolization of colorectal cancer metastases: comorbidities or older age do not affect overall survival

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Ricarda Seidensticker ◽  
Robert Damm ◽  
Julia Enge ◽  
Max Seidensticker ◽  
Konrad Mohnike ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Older Age ◽  
Local Ablation ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

scholarly journals Prognostic factors for patients treated with abiraterone

2020 ◽  
Vol 6 (2) ◽  
pp. FSO436 ◽  
Author(s):  
Cecília M Alvim ◽  
André Mansinho ◽  
Rita S Paiva ◽  
Raquel Brás ◽  
Patrícia M Semedo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Hazard Ratio ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Prognostic And Predictive Factors

Aim: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Methods: Retrospective evaluation of patients with mCRPC treated with AA. Results: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10−0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14−0.41; p < 0.001). Conclusion: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.

scholarly journals Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer

2019 ◽  
Vol 47 (5) ◽  
pp. 1829-1842 ◽  
Author(s):  
Weimin Xu ◽  
Yilian Zhu ◽  
Wei Shen ◽  
Wenjun Ding ◽  
Tingyu Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
T Stage ◽  
Cdx2 Expression ◽  
Prognostic Prediction ◽  
Disease Free

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.

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