Adjuvant Treatment Of Colon Cancer Research Articles

The Role of Capecitabine in Locally Advanced Rectal Cancer Treatment

Preoperative infusional 5-fluorouracil (5-FU) and concurrent radiation therapy (RT) followed by total mesorectal surgery is the current standard of care for locally advanced rectal cancer (LAR). When compared with postoperative 5-FU-based chemoradiation, this strategy is associated with significantly lower rates of local relapse, lower toxicity and better compliance. Capecitabine is a rationally designed oral prodrug that is converted into 5-FU by intracellular thymidine phosphorylase. Substitution of infusional 5-FU with capecitabine is an attractive option that provides a more convenient administration schedule and, possibly, increased efficacy. Indeed, incorporation of capecitabine in combined modality neoadjuvant therapy for LAR has been under intense investigation during the last 10 years. Phase I and II clinical trials showed that a regimen consisting of capecitabine 825mg/m(2) twice daily for 7 days/week continuous oral administration in combination with RT is an active and well tolerated regimen, thereby being the preferred concurrent regimen. The definitive demonstration that efficacy of capecitabine/RT is similar to 5-FU/RT has been provided by the NSABP-R-04 and the German Margit trials. One approach to improve outcomes in rectal cancer is to deliver a second RT-sensitizing drug with effective systemic activity. Oxaliplatin and irinotecan are therefore good candidates. However, two phase III trials demonstrated that incorporation of oxaliplatin to capecitabine with RT did not improve early outcomes and, by contrast, increased toxicity. Capecitabine has also been combined with irinotecan. This regimen showed encouraging results in phase I and II clinical trials, which led to an ongoing phase III clinical trial. New strategies with induction chemotherapy with or without chemoradiation prior to surgery are currently under investigation. Whether or not capecitabine has a role in this setting is being investigated in ongoing trials. Incorporation of agents directed towards new targets, such as anti-epidermal growth factor receptor (EGFR) antibodies or antiangiogenic agents, in combination preoperative regimens, is being hampered by results of early trials in which efficacy outcomes with cetuximab were poor and an excessive rate of surgical complications with bevacizumab was observed. The lack of improvements in efficacy with the addition of cetuximab or bevacizumab in the adjuvant treatment of colon cancer led to concerns about further development of these agents in rectal cancer. The role of capecitabine in the postoperative adjuvant setting is the aim of the ongoing Dutch SCRIPT trial. The prediction of response associated with capecitabine has been based on expression of thymidylate synthase and dihydropyrimidine dehydrogenase, as well as on gene expression arrays. All these procedures require further validation and should be considered as investigational. In conclusion, capecitabine can safely and effectively replace intravenous continuous infusion of 5-FU in the preoperative chemoradiation setting for rectal cancer management. The addition of other new antineoplastic agents to a fluoropyrimidine-based regimen remains investigational.

FOLFOX4 in the adjuvant treatment of colon cancer in Asian patients.

Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Surgery is the only way to potentially cure the disease and may be accomplished in 70% to 80% of newly diagnosed cases. However, 40% to 50% of patients who undergo surgery alone ultimately relapse and die of metastatic disease. Adjuvant chemotherapy, which has been developed to reduce the recurrence of CRC, has evolved from the single agent fluorouracil (5FU) to combinations with oxaliplatin, which now have an established role in stage III CRC. FOLFOX4 has been widely used as an adjuvant treatment of CRC, including the Asia-Pacific region. Adjuvant chemotherapy for CRC has been extensively investigated in the West but whether treatment outcomes in Asian individuals vary due to racial differences is uncertain. Racial differences should be considered, and differences in outcomes have been shown in patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors. This article critically reviews the evolution of adjuvant chemotherapy in CRC and focuses on the side effects of FOLFOX4 when administered to Asian patients for the adjuvant treatment of CRC. Comparisons of the tolerability of FOLFOX4 in different races from well-designed studies conducted in the West and Asia will be reviewed.

Comparative Effectiveness of Oxaliplatin vs Non–Oxaliplatin-containing Adjuvant Chemotherapy for Stage III Colon Cancer

The addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain. Patients younger than 75 years with stage III colon cancer who received chemotherapy within 120 days of surgical resection were identified from five observational data sources-the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER-Medicare), the New York State Cancer Registry (NYSCR) linked to Medicaid and Medicare claims, the National Comprehensive Cancer Network (NCCN) Outcomes Database, and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS). Overall survival (OS) was compared among patients treated with oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy. Overall survival for 4060 patients diagnosed during 2004-2009 was compared with pooled data from five RCTs (the Adjuvant Colon Cancer ENdpoinTs [ACCENT] group, n = 8292). Datasets were juxtaposed but not combined using Kaplan-Meier curves. Covariate and propensity score adjusted proportional hazards models were used to calculate adjusted survival hazard ratios (HR). Stratified analyses examined effect modifiers. All statistical tests were two-sided. The survival advantage associated with the addition of oxaliplatin to adjuvant 5-FU was evident across diverse practice settings (3-year OS: RCTs, 86% [n = 1273]; SEER-Medicare, 80% [n = 1152]; CanCORS, 88% [n = 129]; NYSCR-Medicaid, 82% [n = 54]; NYSCR-Medicare, 79% [n = 180]; and NCCN, 86% [n = 438]). A statistically significant improvement in 3-year overall survival was seen in the largest cohort, SEER-Medicare, and in the NYSCR-Medicare cohort (non-oxaliplatin-containing vs oxaliplatin-containing adjuvant therapy, adjusted HR of death: pooled RCTs: HR = 0.80, 95% CI = 0.70 to 0.92, P = .002; SEER-Medicare: HR = 0.70, 95% CI = 0.60 to 0.82, P < .001; NYSCR-Medicare patients aged ≥65 years: HR = 0.58, 95% CI = 0.38 to 0.90, P = .02). The association between oxaliplatin treatment and better survival was maintained in older and minority group patients, as well as those with higher comorbidity. The addition of oxaliplatin to 5-FU appears to be associated with better survival among patients receiving adjuvant colon cancer treatment in the community.

A Case of Therapy-Related Acute Myeloid Leukemia Following 5-Fluorouracil Chemotherapy

A Case of Therapy-Related Acute Myeloid Leukemia Following 5-Fluorouracil Chemotherapy

Cost-Effectiveness of Adjuvant FOLFOX Therapy for Stage III Colon Cancer in Japan Based on the MOSAIC Trial

ObjectiveTo evaluate the cost-effectiveness of adjuvant FOLFOX therapy versus 5-fluorouracil/leucovorin (FU/LV) for patients with stage III colorectal cancer. MethodsWe performed the cost-effectiveness of FOLFOX compared with standard FU/LV treatment by the retrospective analysis of patient-level data from the randomized controlled Multicenter International Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) trial. Predicted mean time spent in each disease state was calculated by our statistical model, which takes into account the cure rate and treats death from causes other than colon cancer as a competing risk. We performed this analysis from the perspective of the health-care payer. Using a time horizon of 30 years, both cost and effectiveness were discounted by 3% per year. ResultsEstimated cure rates for colon cancer were 0.715 (FOLFOX) and 0.622 (FU/LV). Estimated medical costs of FOLFOX were JPY 3.1 million (USD 34,000) compared with JPY 1.9 million (USD 22,000) of FU/LV. The mean estimated quality-adjusted life-year was 9.83 with FOLFOX and 9.07 with that of FU/LV. The incremental cost-effectiveness ratio of FOLFOX was JPY 1.5 million (USD 17,000) per quality-adjusted life-year compared with FU/LV, which was supported by sensitivity analysis. Even if we assume that Japanese outcomes were better than those reported by the MOSAIC trial, which would reduce the difference between cure rates for each treatment to 5%, the incremental cost-effectiveness ratio remained below 5.0 million (USD 56,000) per quality-adjusted life-year. ConclusionsAdjuvant FOLFOX is a cost-effective treatment for stage III colon cancer in Japan compared with FU/LV therapy. Even when parameters were changed to reflect smaller improvements with FOLFOX, the conclusion is the same.

The Evolution of Adjuvant Therapy in the Treatment of Early-Stage Colon Cancer

Adjuvant treatment of colon cancer, one of the most common malignancies, is an important issue in oncology. This article describes the development of adjuvant therapy and how the 2 major evolution steps, the successes of fluoropyrimidines, and then of oxaliplatin, have been achieved, Problems and failures, such as those of targeted therapies, also are addressed to help us to overcome their limitations. Special situations, such as stage II disease and an elderly population in which adjuvant chemotherapy is still controversial, are reviewed from the clinician perspective. The synthesis of these data allows us to conceive a future development focused on translational research.

Safety Analysis of FOLFOX4 Treatment in Colorectal Cancer Patients: A Comparison Between Two Asian Studies and Four Western Studies

Oxaliplatin-based therapy, notably FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin), is a standard regimen approved globally for the treatment of metastatic colorectal cancer, and as adjuvant treatment of colon cancer. As part of the Japanese submission for the adjuvant indication, the safety profile of FOLFOX4 regimen was compared in Asian and Western patients. A total of 3359 patients with colorectal cancer treated with the FOLFOX4 regimen were included in the analyses: 1515 from 2 Asian studies (Japanese Post Marketing Surveillance and Multicenter Asia Study in Adjuvant Treatment of Colon Cancer with Oxaliplatin/5-FU/LV), and 1844 from 4 Western studies (EFC2962, N9741, EFC4584, and Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer). Doses administered and safety parameters were analyzed by using common definitions and programs. Demographic and baseline characteristics were comparable between Asian and Western patients. Patients received FOLFOX4 for a median of 6-12 cycles, which ranged from 16 to 28 weeks. Median dose intensities of oxaliplatin and of 5-fluorouracil, bolus and infusion, were within the ranges of 33 to 36 mg/m(2)/week, 297 to 338 mg/m(2)/week, and 467 to 510 mg/m(2)/week, respectively. Most frequently reported adverse events (AE) included hematologic, gastrointestinal, and neurosensory adverse events (NSAE). The incidence of grade ≥3 neutropenia ranged from 37% (422 of 1134) to 52% (83 of 159) in Asian and 41% (455 of 1108) to 56% (144 of 259) in Western studies; of diarrhea, ranged from 1.4% (3 of 222) to 6.3% (10 of 159) and 11% (30 of 268 or 120 of 1108) to 14% (36 of 259); of NSAEs, from 1.9% (21 of 1134) to 4.4% (7 of 159) and 9.3% (25 of 268) to 19% (39 of 209); and of allergic reactions, from 0.6% (7 of 1134) to 3.1% (5 of 159) and 1.1% (3 of 268) to 3.0% (33 of 1108), respectively. The probability of grade ≥3 NSAEs and diarrhea was statistically significantly lower in Asian than in Western studies by using a log-rank test. There was no evidence that Asian patients experienced worse toxicity than did Western patients when treated with FOLFOX4, and trends toward reduced neurotoxicity and diarrhea among Asian patients were observed.

Oxaliplatin in the adjuvant treatment of colon cancer

Oxaliplatin in the adjuvant treatment of colon cancer

Recommendations and expert opinion on the adjuvant treatment of colon cancer in Spain

Adjuvant chemotherapy is the current standard in the management of patients with localised colon cancer (CC) following curative resection. The use of oxaliplatin plus 5 fluorouracil/leucovorin (FOLFOX) or oxaliplatin plus capecitabine-based (XELOX) regimens, both approved in Europe as adjuvant treatment for stage III CC, has improved prognosis in this stage, but questions on their usefulness in high-risk stage II or elderly CC patients and on the role of some prognostic biomarkers are still pending. In April 2010, a consensus meeting on adjuvant CC treatment based on a revision of the most recent literature was held in Spain. The panel considered the use of adjuvant chemotherapy for high-risk stage II CC patients to be justified. Additionally, the more convenient administration of oral fluoropyrimidines vs. IV continuous infusion 5-FU would make XELOX a more suitable alternative for the patient. A more cautious decision should be taken when prescribing oxaliplatin treatment in patients aged ≥70.

Outcomes Among Black Patients With Stage II and III Colon Cancer Receiving Chemotherapy: An Analysis of ACCENT Adjuvant Trials

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

Adjuvant Chemotherapy in Colon Cancer: Ageism or Appropriate Care?

Adjuvant Chemotherapy in Colon Cancer: Ageism or Appropriate Care?

Adjuvant treatment of colon cancer: what is next?

Since 2003, fluorouracil/leucovorin plus oxaliplatin (FOLFOX) has been the standard of care in adjuvant therapy. This review reports the results of recent phase III trials which have attempted to improve upon the existing standard of care in adjuvant therapy. In addition, we examine how results of these trials have shaped our knowledge and outline directions for future research. The demonstrated efficacy of adding irinotecan, bevacizumab, or cetuximab to fluorouracil-based regimens in the treatment of patients with metastatic colorectal cancer led to several multicenter phase III trials investigating the efficacy of these agents in the adjuvant setting. In the last 2 years, all of these trials have reported failures to improve patient outcomes, and the field has remained essentially static. Negative results from multiple phase III trials suggest that the existing paradigm for the selection of agents to use in adjuvant trials is deeply flawed. Moving forward, we need to ensure mechanistic rationale for clinical trial design and reassess whether disease-free survival is the primary endpoint that should be used to evaluate biologic agents. Future research should be directed toward the development of prognostic and predictive markers for the development of a data-driven roadmap to inform risk stratification and therapeutic decision-making.

Cost-minimization analysis (CMA) of capecitabine plus oxaliplatin (XELOX) compared with modified FOLFOX6 (mFOLFOX6) for the adjuvant treatment of resected colon cancer in British Columbia.

e16538 Background: Evidence suggests that XELOX (NO16968 XELOXA) may have similar efficacy as mFOLFOX6 in the adjuvant treatment of colon cancer. Because XELOX is partly administered orally and is associated with a 3-week rather than a 2-week treatment cycle, we conducted a CMA from the healthcare payer and societal perspectives in order to evaluate the potential cost savings of replacing mFOLFOX6 with XELOX in the province of British Columbia, Canada. Methods: Applying treatment and toxicity data from phase III clinical trials of XELOX and FOLFOX-based regimens to the adjuvant colon cancer population in British Columbia, the CMA compared total costs associated with chemotherapy medications, drug administration and delivery, hospital and clinic visits, treatment-related toxicities, and need for central venous access devices (CVADs). Costs to patients in terms of lost time and decreased travel were also considered. We assumed that patients would receive either 8 cycles of XELOX or 12 cycles of mFOLFOX6 in our cost models. Results: The different costs by type are summarized in the table. From the payer perspective, the use of XELOX resulted in cost savings of $5,339 per patient when compared to mFOLFOX6. From a societal perspective, XELOX was also associated with savings of $6,082 per patient. The greatest cost savings with XELOX were attributed to fewer visits for chemotherapy treatment and decreased CVAD usage. XELOX was also associated with less loss of time and decreased travel for patients because of fewer clinic visits. Conclusions: Replacing mFOLFOX6 with XELOX in the adjuvant treatment of colon cancer may be associated with potential cost savings from both the payer and societal perspectives. Cost items (all in CAD currency) XELOX mFOLFOX6 Incremental difference Drug costs $24,280 $25,399 Administration costs $1,647 $3,302 Hospitalization costs $2,172 $3,163 Clinic costs $107 $121 Toxicity costs $82 $78 Central venous access costs $194 $1,757 Total costs - payer $28,484 $33,823 - $5,339 Patient time costs $2,745 $3,257 Patient travel costs $1,116 $1,345 Total costs - societal $32,345 $38,427 - $6,082

A multinational, randomized phase III study of bevacizumab (Bev) with FOLFOX4 or XELOX versus FOLFOX4 alone as adjuvant treatment for colon cancer (CC): Subgroup analyses from the AVANT trial.

3509 Background: The therapeutic impact of Bev plus either FOLFOX4 or XELOX in the adjuvant setting was evaluated in the AVANT trial. First efficacy findings were presented at ASCO GI 2011. Here we present results of subgroup analyses. Methods: Eligible pts underwent resection for resected high-risk stage II or stage III CC. Pts were randomly assigned to 1 of 3 treatment groups and stratified by geographic region and tumor stage: Arm A: FOLFOX4 w1–24; Arm B: FOLFOX4 + Bev w1–24, then Bev alone w25–48; Arm C: XELOX + Bev w1–24, then Bev alone w25–48. The primary endpoint was disease-free survival (DFS) for stage III CC; secondary endpoints included overall survival (OS) and safety. DFS/OS follow-up assessments were performed every 6m after randomization for 4y, then annually until recurrence/death. Results: 3,451 (2,867 stage III CC) pts were enrolled between Dec 2004 and Jun 2007; median age was 58–59y. Median duration of follow-up was 48m (range 0–66). Adding Bev did not prolong DFS with FOLFOX4 (HR 1.17; 95% CI 0.98–1.39) or XELOX (HR 1.07; 95% CI 0.90–1.28); the chemotherapy alone arm was favored numerically. Key subgroup findings for DFS in stage III pts are presented below (Table). Conclusions: Subgroup analysis results for DFS were consistent with those seen in the overall stage III CC population. Follow-up is ongoing for OS analysis. Subgroups FOLFOX4 n=955 FOLFOX4 + Bev n=960 XELOX + Bev n=952 n n HR (95% CI) n HR (95% CI) Gender Male Female 530 425 487 1.07 (0.85–1.35) 473 1.32 (1.01–1.71) 520 1.04 (0.83–1.31) 432 1.11 (0.84–1.47) Age, y <65 ≥65 <70 ≥70 680 275 833 122 699 1.14 (0.93–1.40) 261 1.26 (0.92–1.73) 848 1.17 (0.97–1.41) 112 1.19 (0.72–1.96) 656 1.00 (0.80–1.24) 296 1.24 (0.91–1.69) 819 1.04 (0.86–1.26) 133 1.28 (0.80–2.06) Race Asian Black White Other 139 6 791 18 115 2.18 (1.29–3.67) 13 0.48 (0.08–2.89) 813 1.09 (0.90–1.32) 18 0.97 (0.31–3.02) 123 1.52 (0.88–2.63) 14 0.27 (0.04–1.97) 795 1.04 (0.86–1.26) 20 1.24 (0.40–3.84) No. of lymph nodes analyzed <12 ≥12 269 684 261 1.26 (0.91–1.75) 695 1.13 (0.92–1.39) 275 1.06 (0.76–1.49) 675 1.08 (0.88–1.34) N stage N1 N2 585 370 590 1.37 (1.07–1.76) 370 0.99 (0.78–1.26) 572 1.14 (0.87–1.48) 380 0.99 (0.78–1.26)

Relationship between physician characteristics and the use of newer chemotherapy for the treatment of colon cancer.

6106 Background: Oxaliplatin has been a standard part of adjuvant colon cancer treatment since 2003, while patients with metastatic cancer receive oxaliplatin and/or irinotecan. We investigated the...

The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute⊕ Study

BackgroundThe presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC). In spite of a potentially curative resection, 20 to 30% of CC patients testing negative for lymph node metastases (i.e. pN0) will subsequently develop locoregional and/or systemic metastases within 5 years. The presence of occult nodal isolated tumor cells (ITCs) and/or micrometastases (MMs) at the time of resection predisposes CC patients to high risk for disease recurrence. These pN0micro+ patients harbouring occult micrometastases may benefit from adjuvant treatment. The purpose of the present study is to delineate the subset of pN0 patients with micrometastases (pN0micro+) and evaluate the benefits from adjuvant chemotherapy in pN0micro+ CC patients.Methods/designEnRoute+ is an open label, multicenter, randomized controlled clinical trial. All CC patients (age above 18 years) without synchronous locoregional lymph node and/or systemic metastases (clinical stage I-II disease) and operated upon with curative intent are eligible for inclusion. All resected specimens of patients are subject to an ex vivo sentinel lymph node mapping procedure (SLNM) following curative resection. The investigation for micrometastases in pN0 patients is done by extended serial sectioning and immunohistochemistry for pan-cytokeratin in sentinel lymph nodes which are tumour negative upon standard pathological examination. Patients with ITC/MM-positive sentinel lymph nodes (pN0micro+) are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS).DiscussionThe EnRoute+ study is designed to improve prognosis in high-risk stage I/II pN0 micro+ CC patients by reducing disease recurrence by adjuvant chemotherapy.Trial RegistrationClinicalTrials.gov: NCT01097265

AVANT: Results from a randomized, three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer.

362 Background: Bevacizumab (BEV), a humanized anti-VEGF monoclonal antibody, has demonstrated clinical efficacy in combination with 5-FU-based regimens in patients with metastatic colorectal cancer. The therapeutic impact of concurrent BEV with either FOLFOX4 or XELOX chemotherapy in the adjuvant setting was evaluated in this international, controlled phase III trial. Methods: Eligible patients had high-risk stage II or stage III colon cancer and had undergone surgical resection. Patients were randomly assigned to one of three treatment groups and stratified by geographic region and tumor stage: Arm A: FOLFOX4 on weeks 1–24; Arm B: FOLFOX4 + BEV on weeks 1–24, then BEV alone on weeks 25–48; Arm C: XELOX + BEV on weeks 1–24, then BEV alone on weeks 25–48. The primary endpoint was disease-free survival (DFS) for patients with stage III colon cancer; secondary endpoints included overall survival (OS), and safety. DFS/OS follow-up assessments were performed every 6 months after randomization for 4 years, then annually until recurrence or death. Results: 3,451 (2,867 stage III) patients were enrolled between December 2004 and June 2007; median age was 58–59 years. Median duration of follow-up was 48 months (range 0–66 months). BEV did not prolong DFS or OS when added to either FOLFOX4 or XELOX in patients with stage III colon cancer based on the final efficacy analysis conducted in September 2010. Efficacy results favored the chemotherapy-alone control arm. Numerically more relapses and deaths occurred in both the BEV arms compared to control. The observed adverse events were consistent with those previously reported in pivotal trials of BEV across tumor types for approved indications. Conclusions: The primary endpoint of the AVANT study was not met. BEV does not prolong DFS when added to either FOLFOX4 or XELOX in patients with stage III colon cancer. The safety profile of BEV was consistent with prior study results. [Table: see text]

Study on the deterioration of verbal memory in colon cancer patients after receiving adjuvant chemotherapy.

509 Background: Usually, patients treated with chemotherapy (CT) complain about memory loss. This was mainly studied on patients receiving adjuvant CT for breast cancer. However there are no data on adjuvant treatment of colon cancer (CC). The aim of this study is to investigate whether adjuvant CT induces in CC patients impaired memory, particularly the verbal one. Methods: 77 patients diagnosed with stage II-III CC who received adjuvant CT for 6 months with FOLFOX-4 were included between January 2008 and May 2010. Verbal memory was investigated pre-and post-treatment by the Test Barcelona. Peña-Casanova, (1990). Results: Data of 54 patients who completed the analysis pre-and post-treatment were collected. Population characteristics are: male (61%), mean age of 66, less than 5 years of education (58.3%), stage II/III (43/57%) treated with FOLFOX-4/Xeloda (85/15%). Analysis of verbal memory performance can be seen in the table. Conclusions: We found a clear verbal memory impairment after adjuvant CT in CC patients, although the number of words Learning decreases without reaching statistical significance. Remembering of stories is significantly deteriorated after the administration of QT, affecting the patient immediate recall of stories, even when given clues. So it is the delayed recall (after 5′). This can have a negative impact on the patient's life in tasks involving immediate or delayed recall of events. This interesting finding must be tested in larger series and placebo controlled randomized trials. [Table: see text] No significant financial relationships to disclose.

A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: A Hellenic Cooperative Oncology Group study

BackgroundColon cancer is a public health problem worldwide. Adjuvant chemotherapy after surgical resection for stage III colon cancer has been shown to improve both progression-free and overall survival, and is currently recommended as standard therapy. However, its value for patients with stage II disease remains controversial. When this study was designed 5-fluorouracil (5FU) plus leucovorin (LV) was standard adjuvant treatment for colon cancer. Irinotecan (CPT-11) is a topoisomerase I inhibitor with activity in metastatic disease. In this multicenter adjuvant phase III trial, we evaluated the addition of irinotecan to weekly 5FU plus LV in patients with stage II or III colon cancer.MethodsThe study included 873 eligible patients. The treatment consisted of weekly administration of irinotecan 80 mg/m2 intravenously (IV), LV 200 mg/m2 and 5FU 450 mg/m2 bolus (Arm A) versus LV 200 mg/m2 and 5FU 500 mg/m2 IV bolus (Arm B). In Arm A, treatments were administered weekly for four consecutive weeks, followed by a two-week rest, for a total of six cycles, while in Arm B treatments were administered weekly for six consecutive weeks, followed by a two-week rest, for a total of four cycles. The primary end-point was disease-free survival (DFS) at three years.ResultsThe probability of overall survival (OS) at three years was 0.88 for patients in Arm A and 0.86 for those in Arm B, while the five-year OS probability was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.436). Furthermore, the probability of DFS at three years was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.334). With the exception of leucopenia and neutropenia, which were higher in patients in Arm A, there were no significant differences in Grades 3 and 4 toxicities between the two regimens. The most frequently recorded Grade 3/4 toxicity was diarrhea in both treatment arms.ConclusionsIrinotecan added to weekly bolus 5FU plus LV did not result in improvement in disease-free or overall survival in stage II or III colon cancer, but did increase toxicity.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12610000148077

Oxaliplatine, fluoro-uracile et leucovorine: traitements adjuvants des cancers du côlon

BackgroundThe standard adjuvant treatment for colon cancer is fluorouracil plus leucovorin (FL). Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer. We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting.MethodWe randomly assigned 2,246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months. The primary end point was disease-free survival.ResultsA total of 1,123 patients were randomly assigned to each group. After a median follow-up of 37.9 months, 237 patients in the group given FL plus oxaliplatin had had acancer-relatedevent, as compared with 293 patients in the FL group (21.1 percent versus 26.1 percent; hazard ratio for recurrence, 0.77; P = 0.002). The rate of disease-free survival at three years was 78.2 percent (95 percent confidence interval, 75.6 to 80.7) in the group given FL plus oxaliplatin and 72.9 percent (95 percent confidence interval, 70.2 to 75.7) in the FL group (P = 0.002 by the stratified log-ranktest). In the group given FL plus oxaliplatin, the incidence of febrile neutropenia was 1.8 percent, the incidence of gastrointestinal adverse effects was low, and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment, decreasing to 1.1 percent at one year of follow-up. Six patients in each group died during treatment (death rate, 0.5 percent).ConclusionAdding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment for colon cancer.