Adjuvant Chemotherapy For Colon Cancer Research Articles

Surrogacy of progression-free survival (PFS) for overall survival (OS) in rectal cancer trials with preoperative therapy: Literature-based meta-analysis.

734 Background: Disease-free survival (DFS) after adjuvant chemotherapy in colon cancer has been validated as a surrogate endpoint for OS. An analysis of individual patient data from two randomized controlled trials evaluating preoperative chemoradiotherapy for rectal cancer has already shown that PFS might be a surrogate endpoint for OS (Eur J Cancer, 2012). However, since the report was derived from only two trials, the further evaluation of surrogacy with a larger number of trials is desirable. This study was conducted to explore the trial level correlations between PFS and OS in resectable rectal cancer with preoperative therapy. Methods: A systematic literature search of randomized trials of preoperative chemoradiotherapy, radiotherapy or chemotherapy for rectal cancer reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R2) within PFS and OS. 95% confidence interval of R2 was estimated by bootstrap method. The primary analysis included trials in which the HR of PFS and OS were reported. A sensitivity analysis included the trials in which either HR or 5 years point estimates of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the point estimates of PFS and OS assuming exponential distribution. Results: Of 1,048 articles, 14 trials (7,233 patients) were selected for the primary analysis and 18 (8,020) for the sensitivity analysis. Median numbers of enrolled patients were 332 (range 113-1,805) in primary analysis, and 296 (113-1,805) in sensitivity analysis. The primary analysis did not show the correlation between treatment effects on PFS and OS(R2 0.408; 95% CI [0.133-0.845]). The sensitivity analysis showed modest correlation between PFS and OS (R2 0.603; 95% CI [0.296-0.871]). Conclusions: The primary analysis showed that PFS was not suitable as a surrogate endpoint, which is contradictory to the previous report. Based on our results, OS is still preferable as the primary endpoint in the trials of preoperative therapy for resectable rectal cancer.

How can we improve adjuvant chemotherapy for colon cancer?

In The Lancet Oncology, Hans-Joachim Schmoll and colleagues1 report an individual patient data pooled analysis from four randomised controlled trials of patients with stage III colon cancer, in which different treatment regimens were used. The authors directly compared chemotherapy regimens involving two different fluoropyrimidine chemotherapy backbones (fluorouracil and leucovorin vs capecitabine), with or without the addition of oxaliplatin. The authors report no relevant differences in disease-free survival (adjusted HR 1·02 [95% CI 0·93–1·11]; p=0·72), relapse-free survival (1·02 [0·93–1·12]; p=0·72), or overall survival (1·04 [0·93–1·15]; p=0·50), irrespective of the base chemotherapy regimen used.

S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial)

S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV). Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. NCT00660894.

577P - Reasons for Delay in Time to Initiation of Adjuvant Chemotherapy for Colon Cancer: a Multi-Institution Study

ABSTRACT Aim: Although adjuvant chemotherapy (AC) has been shown to improve survival in patients with colon cancer (CC), meta-analyses have suggested decreased survival with increasing Time To AC (TTAC). We examined the predominant factors leading to delayed TTAC in routine clinical practice. Methods: Individual medical records were reviewed for 1,608 patients with CC who initiated AC 2005-2012 at eight cancer centers in the Province of Ontario. Patient, disease, and treatment characteristics, plus time intervals between each step in the cancer care pathway from surgery to AC, were captured. Patients were then categorized into three groups for comparison: (I) inter-current illness and/or post-operative complications, (II) oncologist/patient-initiated delay, (III) no medical reason for delay. Groups were compared using chi square tests and one-way ANOVA. A multivariate logistic regression analysis (MVA) was used to determine factors associated with TTAC >8 weeks (wks) for each cohort. Results: The proportion of patients in each group was: (I) 24.7%, (II) 19.5%, (III) 55.8%; mean TTAC was: (I) 10.1 ± 2.7, (II) 10.5 ± 3.6, (III) 8.5 ± 2.1 wks (p>0.001); the proportion of cases with TTAC>8 wks was: (I) 76.4%; (II) 81.4%; (III) 57.9%. The most common post-operative complication in Group I was ileus (34.2%). The only significant predictor of TTAC >8 wks by MVA in group I was AC via central venous catheter (OR = 2.4, 95%, CI:1.2-4.9). Median length of stay in hospital after surgery was 10, 6 and 6 days for Group I, II, and III, respectively (p Conclusions: Although the majority of patients had no medical reason for delay, the average TTAC was > 8 wks. Our findings suggest that health-system factors such as waiting for consultations and chemotherapy booking cause the majority of delays in TTAC. These are modifiable and quality improvement initiatives should focus on how to reduce these delays. Disclosure: R. Burkes: Research Funding by Sanofi for myself; C. Brezden-Masley: Research Funding by Sanofi for myself; K. Zbuk: Honoraria Yes by Sanofi for myself. All other authors have declared no conflicts of interest.

504PD - Three or Six Months of Adjuvant Chemotherapy for Colon Cancer: Compliance and Safety of the Phase III Italian Tosca Trial

ABSTRACT Aim: Six months FOLFOX4 or XELOX is the standard adjuvant chemotherapy in radically resected stage III colon cancer, however a shorter duration of therapy could be equally efficacious. Methods: This is an Italian, multicenter, non-inferiority phase III trial randomizing patients (pts) with stage III and high risk stage II colon cancer to receive 3 (arm 3) vs 6 (arm 6) months of FOLFOX4 or XELOX. Primary end-point is relapse free survival (RFS), and the arm 3 will be considered non-inferior if the superior margin of the 95% CI of the HR is Results: From June 2007 to March 2013, 3,759 patients were accrued and 3,738 (1860 in arm 3 and 1878 in arm 6) included in the intent-to-treat (ITT) population, since 21 pts were excluded due to major violations. The proportion of FOLFOX4 vs XELOX was 64% vs 36% in both arms. Among the ITT population, demographic factors (including gender and age) were balanced in the two arms. As expected, compliance was higher in arm 3 than in arm 6: treatment completion rate without any modification of planned dose and timing was 35% in arm 3 and 12% in arm 6, while approximately 55% pts in both arms completed treatment with modifications of dose and/or timing, resulting in 90% vs 67% pts receiving all the planned cycles. Therapy was permanently interrupted due to toxicity in 5% of pts in arm 3 and 17% in arm 6. The overall incidence of grade 3-4 toxicity (including grade 2 oxaliplatin neurotoxicity) events was 37% in arm 3 and 60% in arm 6. Grade 2+ neuropathy was more frequent in arm 6 than in arm 3: 32 % vs 9%, respectively. With a median follow-up of 30 months, 476 pts relapsed, 195 died and 520 relapsed and/or died. Conclusions: TOSCA is the first trial completing the accrual among the international initiative of comparing 3 vs 6 months of adjuvant treatment in colon cancer (IDEA). In general, reported toxicity was low, but, as expected, significantly higher in the 6-month arm compared to that of the 3-month arm; accordingly, compliance was lower in the standard 6-month arm. Data for efficacy analysis are premature. Disclosure: All authors have declared no conflicts of interest.

Reasons for Delay in Time to Initiation of Adjuvant Chemotherapy for Colon Cancer.

Adjuvant chemotherapy (AC) improves survival among patients with colon cancer (CC). Two meta-analyses have demonstrated a decrease in survival with increasing time to AC (TTAC). Here, we examine the predominant factors leading to delay in TTAC. Individual medical records of 580 patients with CC who initiated AC August 2005-November 2010 at two large academic cancer centers in Eastern Ontario were reviewed. Information regarding patient, disease, and treatment characteristics, including time intervals between each step in the cancer care pathway from surgery to AC, was captured. Patients were then categorized into three groups for comparison: (I) postoperative complication, (II) oncologist- or patient-initiated delay, (III) no delay. These groups were compared using χ(2) tests and one-way analysis of variance. A multivariable logistic regression model was used to determine factors associated with TTAC > 8 weeks in all patients and in group 1 alone. TTAC among the three groups was (I) 10.1 ± 2.7 weeks, (II) 10.5 ± 3.6 weeks, (III) 8.5 ± 2.1 weeks (P < .001). The only significant predictor of TTAC > 8 weeks on multivariable analysis in group I was route of AC via central venous catheter (odds ratio [OR] = 2.4; 95% CI, 1.2 to 4.9). When multivariable analysis was performed on all patients, the presence of postoperative complications (OR = 2.4; 95% CI, 1.6 to 3.8) and oncologist- or patient-initiated delay were the strongest predictors of delay (OR = 3.5; 95% CI, 2.1 to 6.0). The percentages of patients with TTAC > 8 weeks were (I) 76.4% (n = 110), (II) 81.4% (n = 92), (III) 57.9% (n = 187). In patients with no reason for delay, most experienced TTAC > 8 weeks. This likely reflects delays in referral, consultation, and chemotherapy booking. These health-system factors are modifiable, and future quality improvement initiatives should focus on how to reduce them.

Laparoscopy mitigates adverse oncological effects of delayed adjuvant chemotherapy for colon cancer.

Delaying initiation of adjuvant chemotherapy more than 8 weeks after surgical resection for colorectal cancer adversely affects overall patient survival. The effect of a laparoscopic surgical approach on initiation of chemotherapy has not been studied. The goal of this study was to determine if a laparoscopic approach to colon cancer resection affects the timing of adjuvant chemotherapy and outcomes. Patients who underwent curative surgery for stage II or III colon cancer and received adjuvant chemotherapy between 2003 and 2010 were identified from a prospectively maintained database. Patients were categorized according to surgical approach: open or laparoscopic. Patient demographics, clinicopathologic variables, postoperative complications, time from surgery to initiation of chemotherapy, and long-term oncologic outcomes were compared. Age, gender, ASA class, BMI, tumor stage, and postoperative complications were similar for laparoscopic and open cases, while length of stay was 2 days shorter for laparoscopic cases (5.4 vs 7.6 days, p < 0.01). The proportion of patients who received adjuvant chemotherapy more than 8 weeks after surgery did not differ between the groups (35.6 % open vs 38.7 % laparoscopic, p = 0.77). In the open group, delay in chemotherapy after surgery was associated with decreased disease-free and overall survival (p = 0.01, 0.01, respectively). However, delay in chemotherapy more than 8 weeks did not affect disease-free or overall survival in the laparoscopy group (p = 0.93, 0.51, respectively). The benefits of quicker recovery after laparoscopic surgery did not translate into earlier initiation of adjuvant chemotherapy in this retrospective study. However, a laparoscopic approach negated the inferior oncologic outcomes of patients who received delayed initiation of chemotherapy.

Reasons for delay in time to initiation of adjuvant chemotherapy for colon cancer: A multi-institution study.

e14504 Background: Although adjuvant chemotherapy (AC) has been shown to improve survival in patients with colon cancer (CC), meta-analyses have suggested decreased survival with increasing Time To...

Tolerability of capecitabine in postoperative adjuvant chemotherapy in colon cancer: A single center study.

e14633 Background: According to Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial, capecitabine has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, w...

Longitudinal study of cognitive dysfunctions induced by adjuvant chemotherapy in colon cancer patients

Chemotherapy can induce cognitive impairment in cancer patients. The main goal of this longitudinal study was to determine the incidence, characteristics, and duration of cognitive dysfunction in patients treated with adjuvant chemotherapy for colon cancer. We assessed cognitive function, quality of life, anxiety and depression, fatigue, and hemoglobin levels in colon cancer patients at three assessment points: pre-chemotherapy (n=81), post-chemotherapy (n=73), and after 6-month follow-up (n=54). All patients were treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) for 6 months. Thirty patients (37%) had cognitive impairment in the pre-chemotherapy evaluation, mainly in processing speed and psychomotor executive function (Trail Making Test A and B). At the end of treatment, the main domain affected was the verbal memory, with an acute decline detected in 56% of patients. Fifty-four percent of the patients improved their dysfunction after 6 months of follow-up, whereas 18 (33%) of them showed worsening in at least one test. Cognitive impairment was most common in older patients and in those with less years of education. Quality of life, anxiety, depression, fatigue, and hemoglobin did not influence the results of the cognitive tests. Adjuvant FOLFOX4 in patients with colon cancer can have a negative effect on verbal memory. This deterioration is usually mild and transient.

Transient increase in serum CEA while on adjuvant chemotherapy for colon cancer: Is this of prognostic importance?

654 Background: Serum Carcinoembryonic Antigen (CEA) is used to monitor response to treatment in metastatic colon cancer. Transient surges in CEA can occur after initiation of chemotherapy and are not associated with worse outcome. There is little data on transient CEA surge in the adjuvant setting. We aimed to review patterns of change in CEA levels with adjuvant chemotherapy and investigate associations between transient rises and patient survival. Methods: A retrospective review of patients in Auckland with a new diagnosis of colon cancer in 2001 or 2005 was reported previously [Murray, NZMJ, 2011]. CEA results immediately pre-chemotherapy, during and up to 9 months post chemotherapy were collected and death data was updated. Increase in CEA during chemotherapy was measured as the maximum change from baseline; values more than 2 (within-person) standard deviations above baseline [Erden, Scand, J Clin Lab Inv, 2008] were classified as increased. An increase was transient if the last recorded CEA post chemotherapy was within 2 sd of baseline. Three patient groups were defined: NI (no increase in CEA); TI (transient increase in CEA); and CI (continuous increase in CEA). Kaplan-Meier methods were used to estimate 5-year survival; Cox regression and log-rank p-values were used to compare survival. Results: Of the 77 patients identified with stage II or III disease who had received adjuvant chemotherapy, 61 had sufficient CEA data to be included. The TI group were younger (median [quartiles]: TI 59 [54, 64]; NI 65 [53, 74]; CI 68 [62, 74]) but a greater proportion were stage II (TI 32%; NI 23%; CI 17%). Patients were followed up for a minimum of 7.3 years (or death). Number of deaths per group were: TI 3/19; NI 9/30; CI 7/12. The 5 year overall survival was: TI 95%; NI 83%; CI 42%. There was no significant difference between TI and NI (p = 0.1), but the confidence interval was wide (HR 0.3; 95% CI (0.07 to 1.5). For CI compared to NI, the HR was 2.8 (95% CI (1.0 to 7.6), p = 0.04). Conclusions: The observation that CEA surge does not signal poorer prognosis will be further examined as part of a separate population-based New Zealand-wide study of colorectal cancer diagnosis, treatment and outcome. Part funded by a Genesis Oncology Trust grant.

Adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer.

626 Background: Established guidelines exist for indications of adjuvant chemotherapy in colon cancer. However, in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer, the benefit of adjuvant chemotherapy remains unproven. We evaluated clinical decision making behind adjuvant chemotherapy for locally advanced rectal cancer patients in our institute. Methods: Patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified. Exclusion criteria were inoperable disease, postoperative, recurrence, or palliative intent. 231 cases were examined retrospectively for the decisions behind giving or withholding adjuvant chemotherapy. Results: 35 (15%) were ineligible for consideration of adjuvant chemotherapy due to disease progression. 38 patients (16.4%) received chemotherapy in the adjuvant setting and 158 patients (68.4%) were potentially eligible for adjuvant chemotherapy, but did not receive it. The majority of clinicians based their decisions on post operative pathology results, and the key factor in decision making was final pathological stage in 65%. Clinicians considered pre-treatment imaging a key factor in only 14% of cases, despite a considerable number of patients being downstaged from a potentially higher initial pre-treatment stage that could have warranted adjuvant treatment. A considerable number of patients (25%) were deemed unfit for adjuvant treatment following neoadjuvant chemoradiotherapy and surgery due to toxicity of combined treatment. Conclusions: This analysis highlights the difficulty in clinical decision making for adjuvant chemotherapy in rectal cancer. The accuracy of pre-treatment staging is difficult to ascertain and its use to justify post operative treatment uncertain. It appears the majority of clinicians in our institute base their decision on post operative pathology. A considerable number of patients were not fit for consideration of adjuvant treatment due to toxicity of previous treatment. Further research is warranted as to the benefits of adjuvant chemotherapy, particularly in a setting where prior treatment already causes significant toxicity.

Colorectal signet-ring cell carcinoma: Responsive to adjuvant chemotherapy but still a poor prognosis.

529 Background: Colorectal signet-ring cell carcinoma (SRCC) has been associated with a poor survival compared to mucinous adenocarcinoma (MC) and the common adenocarcinoma (AC). Prognostic impact of tumor localization is unknown and efficacy of adjuvant chemotherapy in SRCC has never been assessed. This study analyses prognostic impact of SRCC and determines whether SRCC patients benefit from adjuvant chemotherapy for colon cancer equally compared with AC. Methods: Data on 196,757 patients with CRC in the Netherlands in the period 1989 and 2010 was included in this nationwide population-based study. Five-year relative survival estimates were calculated and multivariate relative survival analyses using a multiple regression model of relative excess risk (RER) were performed. Results: SRCC was found in 1.0% of CRC patients. SRCC patients presented more frequently with stage III or IV disease than AC (75.2% versus 43.6%, P&lt;0.0001) and SRCC was more frequently found in the proximal colon (57.7% versus 32.0%, P&lt;0.0001). SRCC patients had a poor 5-year relative survival of 31% in colon and 20% in the rectum compared to 57% and 59% in AC (P&lt;0.0001). This poorer survival for SRCC was found in stage II, III and IV. In comparison with AC, there was no significant interaction between SRCC and adjuvant chemotherapy (RER 1.10, 95% CI 0.81-1.51), suggesting a comparable benefit from adjuvant chemotherapy in AC and SRCC. Conclusions: Prognostic impact of SRCC is dismal in both colon and rectal cancer patients, but colonic SRCC patients seem to benefit from adjuvant chemotherapy equally compared with AC. Reduced efficacy of adjuvant chemotherapy therefore does not seem to explain the poor outcome in SRCC patients. We recommend to adhere to adjuvant treatment guidelines for all histological subtypes, but encourage clinical trials to take histological subtype into account for stratification.

High miR-21 expression from FFPE tissues is associated with poor survival and response to adjuvant chemotherapy in colon cancer

Colon cancer (CC) is a leading cause of cancer mortality. Novel biomarkers are needed to identify CC patients at high risk of recurrence and those who may benefit from therapeutic intervention. The aim of this study is to investigate if miR-21 expression from RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue sections is associated with prognosis and therapeutic outcome for patients with CC. The expression of miR-21 was measured by quantitative reverse transcriptase-polymerase chain reaction in a Japanese cohort (stage I-IV, n = 156) and a German cohort (stage II, n = 145). High miR-21 expression in tumors was associated with poor survival in both the stage II/III Japanese (p = 0.0008) and stage II German (p = 0.047) cohorts. These associations were independent of other clinical covariates in multivariable models. Receipt of adjuvant chemotherapy was not beneficial in patients with high miR-21 in either cohort. In the Japanese cohort, high miR-21 expression was significantly associated with poor therapeutic outcome (p = 0.0001) and adjuvant therapy was associated with improved survival in patients with low miR-21 (p = 0.001). These results suggest that miR-21 is a promising biomarker to identify patients with poor prognosis and can be accurately measured in FFPE tissues. The expression of miR-21 may also identify patients who will benefit from adjuvant chemotherapy.

Adjuvant chemotherapy in colon cancer: Can we improve quality of care?

At the beginning of nineties, the treatment of high-risk radically resected colon cancer changed dramatically: in fact, the 1990 NIH Consensus Conference suggested an adjuvant 5-fluorouracil-based chemotherapy as the standard of care for all medically fit patients with resected stage III colon cancer. The same treatment could be considered also in patients with high-risk stage II disease; high-risk patients were defined by pathological factors such as a small number of sampled lymph nodes, T4 lesions, perforation or poorly differentiated histology [1].

Efficacy and safety of single agent (SA) or combination (CO) adjuvant chemotherapy (AC) in elderly patients with colon cancer: A Canadian Cancer Institute experience.

e14715 Background: AC for colon cancer is recommended in the fit elderly. The pattern of AC use in elderly patients (pts), the toxicity profile, and survival benefit is unclear. We sought to: 1) determine whether patients ≥65 years old with stage III colon cancer were being offered SA or CO AC; 2) evaluate the reason for selecting SA vs. CO AC; 3) evaluate the toxicity profile of SA and CO in the elderly; and 4) determine whether a survival benefit exists for elderly pts receiving CO AC. Methods: Pts ≥65 diagnosed with stage III colon cancer at the Cross Cancer Institute from 2004-2010 were identified from the provincial cancer registry. A retrospective analysis of electronic and paper patient records was performed to identify baseline characteristics, AC protocols used, toxicity, dose reductions, dose delays and survival. Results: 258 pts ≥65 years old were diagnosed and treated with AC from 2004-2010. Of these, 168 were treated with SA and 90 with CO AC. The most common reasons for choosing SA AC were patient preference (64%), comorbidities (17%), and lack of drug coverage by provincial formulary (16%). 93 pts ≥age 75 were treated with SA AC, whereas only 20 pts ≥75 were treated with CO AC. Grade 3 and 4 non-hematologic toxicity was more common with CO AC (43% vs. 27%). 20% of all pts had initial dose reductions, with most common reasons being age and comorbidities. 67%, 71% and 29% received dose delays, reductions or drug discontinuation in the SA group, respectively. 72%, 58% and 34% received dose delays, reductions or drug discontinuation in the CO group respectively. 76% of pts received ≥75% of the expected cumulative dose in the SA group, and 81% in the CO group. The 5 year overall survival (OS) of pts who received &lt;75% of expected AC cycles was 63%, compared to 79% in those who received &gt;75% of expected cycles. The 5 year OS was 73% in pts who received SA AC, compared to 84% in those who received CO AC. Conclusions: In elderly pts treated with AC for stage III colon cancer, SA AC is used more frequently than CO AC, based on age, comorbidities, and patient choice. Toxicity with CO AC in elderly pts is high, but may carry a potential a survival benefit for those who receive it.

Study protocol of the B-CAST study: a multicenter, prospective cohort study investigating the tumor biomarkers in adjuvant chemotherapy for stage III colon cancer

BackgroundAdjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied.Methods/designThe B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients’ clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative.DiscussionA total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results of the study will identify the predictors of benefit from each 5-FU derivative, and will contribute to establish the “personalized therapy” in adjuvant chemotherapy for colon cancer.Trial registrationClinicalTrials.gov: NCT00918827, UMIN Clinical Trials Registry (UMIN-CTR) UMIN000002013

Uptake of adjuvant chemotherapy for colon cancer in older and younger patients in the Irish population.

478 Background: Colon cancer is predominantly a disease of the elderly, with recent evidence supporting the use of adjuvant chemotherapy in the older population. However, it remains unclear to what degree such patients are receiving adjuvant therapy in clinical practice. We examined uptake of adjuvantchemotherapy and it’s impact on survival in older patients with stage II and stage III colon cancer in a national cohort. Methods: Using the National cancer Registry of Ireland, we identified 3,486 patients with stage II and III colon cancer who were treated with curative resection from 2004-2009. Clinopathological features and chemotherapy use were compared between those ≥70 years and those &lt; 70 years. Results: A total of 2,026 patients with stage II disease were identified, 56% male and 60% ≥ 70 years. T3 tumors accounted for 81%, T4 19% and 89% were grade 2/3. Adjuvant chemotherapy was utilized in 10% and 40% of ≥ 70 and &lt;70 years, respectively (p&lt;0.0001). A benefit for chemotherapy over observation alone was seen in both the older [HR 0.36; 95% CI 0.36 – 0.68; p &lt;0.0001] and younger patient groups [HR 0.43; 95% CI 0.2701 - 0.6881; p&lt;0.0004]. Of 1,460 patients with stage III disease, 51% were ≥ 70 years, 54% male. 34% of older and 83% of younger patients received adjuvant therapy (p&lt;0.0001). A similar magnitude of benefit from chemotherapy compared to observation was seen in patients ≥ 70 years [HR 0.30; 95% CI 0.29 - 0.45 ; p &lt;0.0001] and &lt;70 years [HR 0.22 95%CI 0.1 – 0.2; p&lt;0.0001] with stage III disease. Conclusions: Adoption of adjuvant chemotherapy appears to be associated with significant survival benefit in older patients (age ≥ 70 years), however, is still underutilized in clinical practice. The impact of sociodemographic and clinicopathological features as potential drivers of treatment decisions in a cohort of this population will be reported.

The effect of age and comorbidity on patient-centered health outcomes in patients receiving adjuvant chemotherapy for colon cancer

While the impact of age, comorbidity and receipt of adjuvant chemotherapy on survival are known, less is known about their effect on patient-centered outcomes including living situation and unplanned health care services. The current study describes the impact of age and comorbidity on patient-centered outcomes in patients with colon cancer. Patients with resected stage III colon cancer and high risk stage II colon cancer were identified from a colorectal cancer center database. Using data collected from chart abstraction, we describe unplanned health care utilization and trajectories of living situation (use of home health, skilled nursing facility, etc.) among high-risk stage II and III colon cancer patients with regard to age categories and receipt of adjuvant chemotherapy. Among 126 eligible patients, 66% received adjuvant chemotherapy and 34% did not. Older patients receiving chemotherapy were more likely to be living independently (81%) compared to those older patients who did not receive chemotherapy (63%). Older patients receiving chemotherapy were less likely to be started on an oxaliplatin-containing regimen compared to younger patients (54% vs. 81%, p=0.02). On multivariate analysis, both diabetes mellitus (OR 3.70 [95% CI 1.3-10.2]) and chronic obstructive pulmonary disease (OR 4.26 [95% CI 1.1-16.0]) were significantly associated with unplanned health care service use. Medical oncologists appear to factor clinical and sociodemographic variables when making recommendations for adjuvant chemotherapy. Older patients deemed eligible for chemotherapy did not experience significant changes in living situation. Among patients with colon cancer receiving adjuvant chemotherapy, diabetes mellitus and COPD are associated with emergency visits and hospital admissions.

A Case of Liver Fibrosis with Splenomegaly after Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer

Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and α-smooth muscle actin (α-SMA) were conducted with control group. The immunohistochemical stains for CD31 and α-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.