Oxaliplatin-based Adjuvant Chemotherapy Research Articles

Considerations regarding an updated meta-analysis of the optimal duration of oxaliplatin-based adjuvant chemotherapy in patients with different risk factors for stage II-III colon cancer.

Considerations regarding an updated meta-analysis of the optimal duration of oxaliplatin-based adjuvant chemotherapy in patients with different risk factors for stage II-III colon cancer.

Optimal duration of oxaliplatin-based adjuvant chemotherapy in patients with different risk factors for stage II-III colon cancer: a meta-analysis.

The duration of oxaliplatin-based chemotherapy in high-risk stage II, low-risk stage III, and high-risk stage III colon cancer (CC) patients is controversial. To reduce the risk of adverse events (AEs) without compromising efficacy while improving chemotherapy compliance is crucial. The authors searched Cochrane, Embase, Pubmed, and Web of Science databases for articles from inception to August 8, 2023, the main outcomes were disease-free survival, overall survival, chemotherapy completion rates, and AE frequency. Six randomized controlled trials (RCTs) involving 10332 patients were included. Disease-free survival analysis revealed that only the high-risk stage III CC patients experienced better results with the 6-month FOLFOX regimen when compared with the 3-month regimen [Hazard ratio (HR): 1.32, 95% CI: 1.15-1.51, P <0.0001). Overall survival (OS) analysis revealed that extending the use of FOLFOX and CAPEOX regimens did not provide survival benefits for stage III CC patients (HR: 1.16, 95% CI: 0.9-1.49, and HR: 0.89, 95% CI: 0.67-1.18, P =0.40). The completion rate of the 3-month oxaliplatin-based adjuvant chemotherapy regimen was significantly higher than that of the 6-month regimen [Relative risk (RR): 1.16, 95% CI: 1.06-1.27, P =0.002]. Moreover, the 3-month regimen had significantly lower AE rates than the 6-month regimen (RR: 0.62, 95% CI: 0.57-0.68, P <0.00001), with differences mainly concentrated in grade 3/4 neutropenia (RR: 0.70, 95% CI: 0.59-0.85, P =0.0002), peripheral sensory neuropathy at ≥grade 2 (RR: 0.45, 95% CI: 0.38-0.53, P <0.00001), and hand-foot syndrome at ≥grade 2 (RR: 0.36, 95% CI: 0.17-0.77, P =0.009). The 6-month FOLFOX regimen should only be recommended for high-risk stage III CC, while the 3-month regimen can be recommended for other stages. A 3-month CAPEOX regimen can be recommended for stage II-III CC.

The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study

BackgroundFor high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers.MethodsPatients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses.ResultsWe collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26–6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06–6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67–4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs.ConclusionsThese data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors.

Development of an improved risk stratification scheme for stage II and III colorectal cancers through incorporation of the digital pathology biomarker QuantCRC.

162 Background: There is a need to improve current risk stratification of stage II and III colorectal cancer (CRC) to better inform risk of recurrence and guide adjuvant chemotherapy. The purpose of this study is to examine whether integration of QuantCRC, an AI-based digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. Methods: ASCO and QuantCRC-integrated risk schemes were applied to an observational cohort of 1,068 stage II and III CRCs. The stage II integrated scheme utilizes pT3 vs. pT4 and QuantCRC-derived risk groups. The stage III integrated scheme utilizes pT1-3 vs. pT4, pN1 vs. pN2, and QuantCRC-derived risk groups. Performance metrics included log-rank test, hazard ratios and Somers’ Dxy rank correlation. Results: Integration of QuantCRC provides improved risk stratification compared to the ASCO scheme for stage II and III CRC. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared to the ASCO scheme (69.3% vs. 60.4%) without decreased 3-year RFS. The QuantCRC-integrated scheme provided larger hazard ratios (HR) for both intermediate-risk (3.04, 95%CI 1.81-5.10, P=2.8x10-5) and high-risk (4.62, 95%CI 2.02-10.61, P=0.0003) groups compared to ASCO intermediate-risk (2.09, 95%CI 1.21-3.63, P=0.008) and high-risk (3.08, 95%CI 1.57-6.01, P=0.001) groups. The QuantCRC-integrated scheme for stage III tumors identified a small group of 80/518 (15.4%) CRCs at very high risk of recurrence with HR of 4.08 (95%CI 2.68-6.23, P=6.5x10-11) compared to a HR of 2.42 (95%CI 1.72-3.38, P=3.1x10-7) for 228/518 (44.0%) high-risk CRCs in the ASCO scheme. QuantCRC-integrated risk groups remained prognostic in stage III CRCs when stratified by presence or absence of any adjuvant chemotherapy. No difference in RFS were seen in QuantCRC-integrated low-risk and intermediate-risk stage III CRCs stratified by 3 vs. 6-months of oxaliplatin-based adjuvant chemotherapy suggesting that these two groups can be treated with 3-months of adjuvant therapy. Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance.

Real-world impact on overall survival of oxaliplatin-based adjuvant chemotherapy in older patients with colorectal cancer in Mexico.

61 Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancer both in Mexico and worldwide, with the peak incidence in patients &gt;65 years. The use of adjuvant chemotherapy (CT) improves the prognosis of high-risk CRC. The benefit from fluorouracil (FU)-based CT across all age groups is not questionable, but the use of oxaliplatin (Ox) is controversial. Methods: Original, retrospective, observational study. Included patients diagnosed with CRC adenocarcinoma treated at the Instituto Nacional de Cancerología México, between 2004 to 2022. Statistical analysis required: X2 and t-test, Kaplan Meier, Log Rank, and Cox Regression. Statistical significance differences were assessed when p was bilaterally &lt;0.05. Results: From 1,238 patients with localized CRC, 275 patients were included in analysis and divided into 2 groups: young (≤ 30 years) (n = 54), and older (≥ 70 years) (n = 221). Most patients were female for both groups (55%). Comorbidities were observed in 2% of young patients and 51% of older patients (p &lt; 0.001). Stages (S) were: II (31%; 39%), and III (59%; 47%). CT was received in 70% of young and 47% of older patients (p = 0.002). Regarding CT regimens, 56% and 21% of young and older patients respectively, had oxaliplatin (p &lt; 0.001), while 21% of young and 32% of older patients did not complete the CT (p = 0.012). Overall survival (OS) analysis was performed considering age and S. S-II median-OS was not reached (NR) for both groups, while S-III median-OS was 170 months (m) for young versus NR for older (p = 0.690). When including CT in OS analysis, patients S-II median-OS was NR for all groups (p = 0.081), while S-III median-OS was 170 m with and 19 m without CT for young versus NR with and 89 m without CT for older, respectively (p = 0.010, 95% CI 0.059-0.123). In S-III older patients, a sub-analysis was performed considering Ox: 10-year-OS was 71% versus 60% for patients treated with and without Ox respectively (p = 0.030, 95% CI 0.25-0.93). In Cox-Regression analysis for patients with clinical stage III, regimen completion (p = 0.004; HR 0.38, 95% CI 0.201-0.745) and Ox (p = 0.022; HR 0.423, 95% CI 0.203-0.881) remained as predictor factors of OS. Conclusions: There are no studies which compare the administration of CT between young and older patients or the description of these populations in Mexico. Young patients are more likely to receive CT with Ox assumingly due to the lack of comorbidities and life expectancy. The benefit of CT on OS in young patients is not in question. An increase in OS was found in older patients who received CT with Ox, but a higher percentage of treatment discontinuation secondary to toxicity. As recommended by the literature, its essential to integrate assessment in older patients to determine which patients will benefit from complete CT regimens to increase their OS, apart from their chronological age.

Adjuvant oxaliplatin-based chemotherapy comparing observation alone after radical resection of metachronous metastases of colorectal cancer: interim analysis

Introduction. Despite the registered standard treatment option for patients who underwent radical resection for metachronous metastases of colorectal cancer (CRC), the feasibility of adjuvant chemotherapy (ACT) for all patients seems controversial. Due to studies demonstrating improved disease-free survival rates with postoperative chemotherapy vs observation, it would seem that there is reasonable expectation of improved overall survival (OS) rates, which, however, were not statistically different between groups. This article presents the interim results of our own study.Aim. To analyse the efficacy of ACT vs dynamic observation in patients who underwent surgery for metachronous metastases of colorectal cancer.Materials and methods. It was a prospective-retrospective, non-randomized, non-inferiority study. A total of 120 patients were recruited between June 2008 and September 2022. The ACT group included 71 patients. All patients received only oxaliplatin-based chemotherapy regimens; the dynamic observation group included 49 patients.Results. The interim analysis showed that the median disease-free survival (mDFS) in the ACT group (n = 71) was 20.9 months (13.7–28.3) vs 24.4 months in the dynamic observation group (n = 49) (11.1–37.7), HR: 0.76 (95% CI: 0.45–1.29), p = 0.29. Two-year disease-free survival (DFS) rates were 46.6% in the post-surgery chemotherapy (CT) group (n = 50) and 55.5% in the experimental group (n = 31), HR: 0.69 (95% CI: 0.39–1.2), p = 0.21.Conclusion. ACT has not improved the long-term treatment outcomes in patients who underwent radical resection for metachronous metastases of CRC.

Impact of the IDEA collaboration study on practice patterns of adjuvant chemotherapy in patients with stage III colon cancer: A population-based study.

533 Background: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration showed no significant clinical difference in outcomes in patients with stage III colon cancer treated with 3 months versus 6 months of oxaliplatin-based adjuvant chemotherapy (O-ACT). We aimed to assess the change in practice patterns of ACT before and after publication of the IDEA study. Methods: This was a retrospective, population-based, cohort study of patients ≥ 18 years of age diagnosed with stage III colon cancer between January 1, 2012 and December 31, 2021 in Alberta, Canada. Eligible patients received &gt;1 dose of ACT. Patients were divided into two groups; pre-IDEA (diagnosed prior to March 31, 2018) and post-IDEA (diagnosed on or after April 1, 2018). Treatment duration was categorized as short (&lt;4.5 months) and long (≥4.5 months). The primary outcome was the median duration and type of ACT and factors associated with a shorter duration of ACT. Two-year overall survival (OS) and cancer-specific survival (CSS) were secondary outcomes. Results: We identified a total of 735 patients. Median age at diagnosis was 64 years (range 27-90 years) and 52.8% (N=388) were male. 48.8% (N=359) patients had had pT4 and/or pN2 disease. 78% (N=572) received O-ACT. In the post-IDEA era, the use of capecitabine plus oxaliplatin (CAPOX) ACT increased (23.0% to 50.9%, p&lt;0.001) and median duration of O-ACT was significantly shorter (2.7 vs 4.8 months, p&lt;0.001). On multivariable logistic regression, factors associated with shorter duration of ACT included treatment in the post-IDEA era (odds ratio [OR] 1.85, p=0.007), no pT4 and/or pN2 disease (OR 1.6, p=0.02), and receipt of CAPOX ACT (OR 2.7, p&lt;0.001). Characteristics not significantly associated with ACT duration included age, sex, residence rurality, neighborhood income, and comorbidity index. The 2-year OS and CSS was similar in the pre-IDEA and post-IDEA eras (OS 95% vs 93%, p=0.29; CSS 96% vs 96%, p=0.30). Neither time era or treatment duration were independently associated with OS or CSS in multivariable models. Conclusions: Our study is one of the first that shows that the results of the IDEA trial have been largely adopted in clinical practice with shorter duration of ACT and increased use of CAPOX ACT in low-risk stage III colon cancer using population-based data.

Oxaliplatin‑induced changes in splenic volume and liver fibrosis indices: retrospective analyses of colon cancer patients receiving adjuvant chemotherapy

The aim of our study was to evaluate the association between increased splenic volume (SV) and liver fibrosis indices in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy. Patients who received adjuvant oxaliplatin-based regimens with the diagnosis of stage II and III colon cancer were evaluated. Splenic volume measurements, liver function tests, platelet count, and non-invasive liver fibrosis indices [NAFLD fibrosis score (NFS), AST to platelet ratio (APRI), and Fibrosis-4 (FIB-4)] were measured before and after treatment. A 30% increase in SV after chemotherapy compared to baseline was considered increased SV. The rate of increase in SV was 57.7% in the whole group. An increase in SV was shown at a higher rate in patients treated with capecitabine and oxaliplatin (CAPOX) than those treated with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) (66.3% vs. 36.8%, p = 0.002). Furthermore, the CAPOX regimen (OR: 2.831, 95% CI: 1.125-7.121; p = 0.027), and higher post-treatment FIB-4 score (OR: 3.779; 95% CI:1.537- 9.294, p = 0.004) were determined as independent risk factors for the increased SV. Our study revealed that increased SV had a significant association with higher FIB-4 score in patients treated with oxaliplatin-based chemotherapy.

Poor Prognosis in Patients With Stage III Colorectal Cancer Receiving Adjuvant FOLFOX/CAPOX Therapy Is Predicted by the Presence of Many Poorly Differentiated Clusters.

Poorly differentiated clusters (PDCs) have been reported to be a useful grading system for predicting prognosis in patients with colorectal cancer (CRC). We investigated the association between the number of PDCs and prognosis in patients with stage III CRC treated with oxaliplatin-based adjuvant chemotherapy. This is a retrospective study of 49 patients with stage III CRC who underwent curative surgery followed by oxaliplatin-based adjuvant chemotherapy. PDC was defined as a cluster of ≥5 cancer cells without glandular structure at the invasive front of the primary tumor. During the observation period, 12 patients experienced relapse. The patients were divided into two groups (<7 and ≥7 PDC groups), and receiver operating characteristic (ROC) curves were calculated [area under the curve (AUC)=0.743]. Patients with ≥7 PDCs had a much shorter relapse-free survival (RFS) than those with <7 PDCs (p<0.0001). The overall survival (OS) was also significantly worse in patients with ≥7 PDCs than in those with <7 PDCs (p<0.0001). Multivariate analysis revealed that PDC was the only significant prognostic factor measured that could predict RFS (p=0.002) and OS (p=0.0047) in patients with stage III CRC treated with oxaliplatin-based adjuvant chemotherapy. In patients with stage III CRC treated with post-resection oxaliplatin-based adjuvant chemotherapeutic regimens, the presence of ≥7 PDCs at the invasive front of the primary tumor predicted unfavorable prognosis.

Sex difference in tolerability of adjuvant oxaliplatin-based chemotherapy for colorectal cancer and changes in diagnostic components of sarcopenia: A prospective study.

e15625 Background: We previously reported that based on CT images at the 3rd lumbar vertebra, female patients with colorectal cancer (CRC) were more likely to be sarcopenic than male patients after curative resection, and predisposed to develop early dose limiting toxicities (DLTs) in adjuvant CAPOX therapy. Although oxaliplatin-based adjuvant chemotherapy for CRC is prevalently used worldwide, it is largely unknown how the treatment affects patients in terms of sarcopenia. Therefore we conducted a prospectively study on the impact of adjuvant chemotherapy on multifactorial components assessed for sarcopenia. Methods: We examined stage II-III CRC patients who received adjuvant CAPOX after curative surgery after March 2022. Informed consent was obtained from all participants. During this systemic therapy, we assessed nutritional status using Mini-Nutritional Assessment (MNA, an 18-item questionnaire consisting of psychological well-being, diet quality, physical activity and anthropometric metrics; score range:0-30), and examined gait speed and grip strength, as well as whole body skeletal muscle mass, fat mass, and bone mineral using a body composition analyzer. The changes in these metrics were analyzed in association with dose reduction/adverse events of CAPOX. All continuous variables were tested by Wilcoxon rank-sum test. Results: Eighteen men and 13 women (mean age: 61 years old) were included in this study. Seven (39%) male and seven (54%) female patients required dose reduction within the four treatment cycles (p = 0.65). The median MNA, gait speed, grip, muscle mass, fat mass and bone mineral at the first and fourth cycles of CAPOX in men were 20.4 and 24.0, 1.10 and 1.23 m/sec, 30.9 and 31.2 kg, 27.3 and 28.0 kg, 11.8 and 11.9 kg, and 2.8 and 2.9 kg, respectively. The median of these metrics at the first and fourth cycles of CAPOX in women were 21.4 and 22.4, 1.32 and 1.33 m/sec, 22.0 and 22.4 kg, 21.95 and 22.12 kg, 13.43 and 14.62 kg, and 2.34 and 2.31 kg, respectively. The relative values (medians) of the metrics at the fourth cycle to those at the first cycle of CAPOX (men vs women) were as follows; MNA:1.131 vs 1.045 (p = 0.057), gait speed:1.075 vs 0.950 (p = 0.17), grip:1.018 vs 1.044 (p = 0.81), muscle mass:1.028 vs 1.011 (p = 0.036), fat mass:1.029 vs 1.080 (p = 0.47), and bone mineral:1.030 vs 0.991 (p = 0.015). Conclusions: It is suggested that adjuvant CAPOX has negative impact on postoperative recovery of psychological and physical components in female patients.

Liver cirrhosis following oxaliplatin-based adjuvant chemotherapy for rectal cancer.

Oxaliplatin is a third-generation platinum-based antineoplastic drug that is widely used to treat patients with colorectal cancer. Reported adverse reactions include hepatic sinusoidal obstruction syndrome and liver fibrosis, but there are few reports of cirrhosis associated with chemotherapy. In addition, the pathogenesis of cirrhosis remains unclear. We report a case of suspected oxaliplatin-induced liver cirrhosis, an adverse reaction that has not been previously reported. A 50-year-old Chinese man was diagnosed with rectal cancer and underwent laparoscopic radical rectal cancer surgery. The patient had a history of schistosomiasis, but history and serology showed no evidence of chronic liver disease. However, after five oxaliplatin-based chemotherapy cycles, the patient presented dramatic changes in liver morphology and developed splenomegaly, massive ascites, and elevated CA125 levels. Four months after discontinuing oxaliplatin, the patient's ascites had decreased significantly and CA125 levels declined from 505.3 to 124.6 mU/mL. After 15 weeks of follow-up, CA125 levels decreased to the normal range, and there has been no increase in ascites in this patient. Oxaliplatin-induced cirrhosis may be a serious complication and should be discontinued based on clinical evidence.

Real-world tolerance and outcomes of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer-Does dose intensity matter?

Fluoropyrimidine and oxaliplatin-based adjuvant chemotherapy delivered as 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), or capecitabine and oxaliplatin (CAPOX) is the standard of care for resected stage III colon cancer. Without randomized trial data, we compared real-world dose intensity, survival outcomes, and tolerability of these regimens. Records of patients treated with FOLFOX or CAPOX in the adjuvant setting for stage III colon cancer across four institutions in Sydney during 2006-2016 were reviewed. The relative dose intensity (RDI) of fluoropyrimidine and oxaliplatin of each regimen, disease-free survival (DFS), overall survival (OS), and incidence of grade ≥2 toxicities were compared. Characteristics of patients receiving FOLFOX (n=195) and CAPOX (n=62) were evenly matched. FOLFOX patients had a higher mean RDI for both fluoropyrimidine (85% vs. 78%, p<0.01) and oxaliplatin (72% vs. 66%, p=0.06). In spite of a lower RDI, CAPOX patients trended toward a better 5-year DFS (84% vs. 78%, HR=0.53, p=0.068) and similar OS (89% vs. 89%, HR=0.53, p=0.21) compared to the FOLFOX group. This difference was most pronounced in the high-risk (T4 or N2) group where 5-year DFS was 78% versus 67% (HR=0.41, p=0.042). Patients receiving CAPOX experienced more grade ≥2 diarrhea (p=0.017) and hand-foot syndrome (p<0.001) but not peripheral neuropathy or myelosuppression. In a real-world setting, patients who received CAPOX had similar OS rates when compared to those receiving FOLFOX in the adjuvant setting in spite of lower RDI. In the high-risk population, CAPOX appears to demonstrate a superior 5-year DFS over FOLFOX.

Preliminary tolerance analysis of adjuvant chemotherapy in older patients after resection of stage III colon cancer from the PRODIGE 34-FFCD randomized trial.

Colon adenocarcinoma mainly occurs in older patients. Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients. The purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma. We report a preliminary tolerance analysis on 50% of the first patients enrolled. The analysis was conducted on 491 patients (378 in Group 1 and 113 in Group 2). Patients in Group 2 were older and showed more frailty criteria than those in Group 1. Cumulative grade 3-5 toxicities were more frequent in patients treated with oxaliplatin in Group 1 or with fluoropyrimidine in Group 2 than in patients treated with fluoropyrimidine in Group 1. At least one course was deferred in more than half of the patients in all groups. Early treatment cessation was more frequent in Group 2. No safety concerns were raised for the continuation of accrual. The frailty criteria distribution suggests that the investigator's evaluation for group allocation was accurate.

Second-line bevacizumab plus FOLFOX in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-based chemotherapy.

157 Background: There is a rarity of evidence for retreatment with oxaliplatin for metastatic colorectal cancer (mCRC), especially in combination with bevacizumab. This is a retrospective study of second line bevacizumab (Bev) plus FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-containing chemotherapy. Methods: Patients with age older than 18 and histologically confirmed metastatic colorectal cancer treated with second line bevacizumab plus FOLFOX in a single institute between 2015 and 2020 were enrolled. History of previous adjuvant chemotherapy regimens in patients with metachronous metastatic colorectal cancer was analyzed. Progression-free survival (PFS) and overall survival (OS) of the second line treatment were calculated using Kaplan-Meier method and compared between patients pretreated with adjuvant oxaliplatin (ReOx) and oxaliplatin-naive patients (control) with the log rank test. Results: A total of 72 patients were included. 23 patients (ReOx) were pretreated with adjuvant oxaliplatin and 49 patients (control) were oxaliplatin-naive before the second line treatment. There was a tendency of younger age in the ReOx group, but not statistically significant. Liver metastasis was significantly more frequent in the control group. The median PFS and OS in the ReOx group and the control group were 4.3 months (95% confidence interval [CI], 3.67–21.50) versus 5.5 months (95% CI, 4.23–8.20, hazard ratio [HR] = 0.84), and 10.5 months (95% CI, 5.40–30.37) versus 9.4 months (95% CI, 6.00–14.9, HR = 1.01) respectively. There was no significant difference of PFS ( p= 0.523) and OS ( p= 0.9745) between two groups. Conclusions: This study suggests a potential survival benefit of bevacizumab plus FOLFOX for mCRC patients previously treated with adjuvant oxaliplatin-containing treatment comparable to oxaliplatin-naive patients. [Table: see text]

Health economic evidence for adjuvant chemotherapy in stage II and III colon cancer: a systematic review

ObjectiveThe aims of this study was to appraise the health economic evidence for adjuvant chemotherapy (AC) strategies in stage II and III colon cancer (CC) and identify gaps in the available evidence that might inform further research.MethodA systematic review of published economic evaluations was undertaken. Four databases were searched and full-text publications in English were screened for inclusion. A narrative synthesis was performed to summarise the evidence.ResultsThirty-eight studies were identified and stratified by cancer stage and AC strategy. The majority (89%) were full economic evaluations considering both health outcomes, usually measured as quality-adjusted life years (QALYs), and costs. AC was found to be cost-effective compared to no AC for both stage II and III CC. Oral and oxaliplatin-based AC was cost-effective for stage III. Three months of CAPOX was cost-effective compared to 6-month in high-risk stage II and stage III CC. Preliminary evidence suggests that biomarker approaches to AC selection in stage II can reduce costs and improve health outcomes. Notably, assessment of QALYs were predominantly reliant on a small number of non-contemporary health-utility studies. Only 32% of studies considered societal costs such as travel and time off work.ConclusionsPublished economic evaluations consistently supported the use of AC in stage II and III colon cancer. Biomarker-driven approaches to patient selection have great potential to be cost-effective, but more robust clinical and economic evidence is warranted. Patient surveys embedded into clinical trials may address critical knowledge gaps regarding accurate assessment of QALYs and societal costs in the modern era.

Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy

The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 (LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.

Impact of Sarcopenia on Patients with Localized Pancreatic Ductal Adenocarcinoma Receiving FOLFIRINOX or Gemcitabine as Adjuvant Chemotherapy.

Despite its toxicity, modified FOLFIRINOX is the main chemotherapy for localized, operable pancreatic adenocarcinomas. Sarcopenia is known as a factor in lower overall survival (OS). The purpose of this study was to assess the impact of sarcopenia on OS in patients with localized pancreatic ductal adenocarcinoma (PDAC) who received modified FOLFIRINOX or gemcitabine as adjuvant chemotherapy. Patients with operated PDAC who received gemcitabine-based (GEM group) or oxaliplatin-based (OXA group) adjuvant chemotherapy between 2008 and 2021 were retrospectively included. Sarcopenia was estimated on a baseline computed tomography (CT) examination using the skeletal muscular index (SMI). The primary evaluation criterion was OS. Secondary evaluation criteria were disease-free survival (DFS) and toxicity. Seventy patients treated with gemcitabine-based (n = 49) and oxaliplatin-based (n = 21) chemotherapy were included, with a total of fifteen sarcopenic patients (eight in the GEM group and seven in the OXA group). The median OS was shorter in sarcopenic patients (25 months) compared to non-sarcopenic patients (158 months) (p = 0.01). A longer OS was observed in GEM non-sarcopenic patients (158 months) compared to OXA sarcopenic patients (14.4 months) (p &lt; 0.01). The median OS was 157.7 months in the GEM group vs. 34.1 months in the OXA group (p = 0.13). No differences in median DFS were found between the GEM group and OXA group. More toxicity events were observed in the OXA group (50%) than in the GEM group (10%), including vomiting (p = 0.02), mucositis (p = 0.01) and neuropathy (p = 0.01). Sarcopenia is associated with a worse prognosis in patients with localized operated PDAC whatever the delivered adjuvant chemotherapy.

Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials.

Oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) for 6 months remains a standard in high-risk stage III patients. Data are lacking as to whether early discontinuation of all treatment (ETD) or early discontinuation of oxaliplatin (EOD) could worsen the prognosis. We studied the prognostic impact of ETD and EOD in patients with stage III CC from the ACCENT/IDEA databases, where patients were planned to receive 6 months of infusional fluorouracil, leucovorin, and oxaliplatin or capecitabine plus oxaliplatin. ETD was defined as discontinuation of treatment and EOD as discontinuation of oxaliplatin only before patients had received a maximum of 75% of planned cycles. Association between ETD/EOD and overall survival and disease-free survival (DFS) were assessed by Cox models adjusted for established prognostic factors. Analysis of ETD and EOD included 10,447 (20.9% with ETD) and 7,243 (18.8% with EOD) patients, respectively. Compared with patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, with Eastern Cooperative Oncology Group performance status ≥ 1, and for ETD, older with a lower body mass index. In multivariable analyses, ETD was associated with a decrease in disease-free survival and overall survival (hazard ratio [HR], 1.61, P < .001 and HR, 1.73, P < .001), which was not the case for EOD (HR, 1.07, P = .3 and HR, 1.13, P = .1). However, patients who received < 50% of the planned cycles of oxaliplatin had poorer outcomes. In patients treated with 6 months of oxaliplatin-based chemotherapy for stage III CC, ETD was associated with poorer oncologic outcomes. However, this was not the case for EOD. These data favor discontinuing oxaliplatin while continuing fluoropyrimidine in individuals with significant neurotoxicity having received > 50% of the planned 6-month chemotherapy.

317MO Efficacy of oxaliplatin-based adjuvant chemotherapy in older patients with stage III colon cancer: An ACCENT/IDEA pooled analysis of 12 trials

317MO Efficacy of oxaliplatin-based adjuvant chemotherapy in older patients with stage III colon cancer: An ACCENT/IDEA pooled analysis of 12 trials

Translation of IDEA trial results into clinical practice: Analysis of the implementation of a new guideline for colon cancer.

The IDEA trial showed no clinical relevant differences in efficacy between 3 and 6 months of oxaliplatin‐based adjuvant chemotherapy (ACT) in colon cancer (CC), while toxicity was substantially lower in the 3 months regimen. Therefore, in 2017 the Dutch colorectal cancer guideline was revised and currently recommends 3 months of oxaliplatin‐based ACT. Furthermore, the definition of high‐risk stage II CC was restricted to pT4 tumors. We analyzed changes in ACT between 2015 and 2019. From the Netherlands Cancer Registry all 16 721 patients ≥18 years with resected high‐risk stage II and stage III CC during 2015 to 2019 were selected. Differences in patient and treatment characteristics were analyzed per calendar year according to stage and age. Mean duration of oxaliplatin‐based ACT decreased from 18.6 (±8.0) to 9.5 (±3.8) weeks between 2015 and 2019. In patients receiving ACT (n = 8170), the proportion treated with oxaliplatin increased from 74% to 83%. The proportion of patients receiving ACT was stable, 61% to 69% in stage III and 26% to 29% in pT4 stage II. ACT in previous high‐risk pT3N0 disease decreased from 15% to 3%. Use of oxaliplatin increased from 27% to 49% in patients aged ≥75 years. The revised guideline was rapidly implemented and led to an increase in oxaliplatin‐based ACT in the elderly and increased guideline‐adherence in high‐risk stage II CC.