Months Of Oxaliplatin-based Chemotherapy Research Articles

Predictive factors of collateral vessel development induced by oxaliplatin-based chemotherapy.

Oxaliplatin can lead to hepatic sinusoidal injury, called hepatic sinusoidal obstruction syndrome (SOS), resulting in portal hypertension-related complications. This could worsen the clinical course of the patients treated with oxaliplatin. Early diagnosis is challenging. We explored predictive markers of oxaliplatin-induced collateral vessels. Patients who received oxaliplatin-based chemotherapy were retrospectively screened. We evaluated their laboratory findings and spleen size on computed tomography immediately before oxaliplatin-based chemotherapy and after 6months of treatment. The primary outcome was collateral vessel development, as a surrogate marker for oxaliplatin-induced SOS in patients who underwent oxaliplatin-based chemotherapy. The secondary outcome was the identification of factors that predicted the development of collateral vessels. We enrolled 161 patients who received oxaliplatin-based chemotherapy. They had a median age of 69years, and 63.3% were men. Collateral vessels developed in nine (5.6%) patients during the study period. After oxaliplatin-based chemotherapy, the spleen size increased in 104 patients (64.6%), with a ≥ 30% increase in 19.4% of the patients. Univariate analysis showed that the Fibrosis-4 (FIB-4) index (≥ 1.76; OR 9.17), aspartate aminotransferase:platelet ratio index (APRI) (≥ 0.193; OR 9.62), cumulative dose of oxaliplatin (≥ 1000mg; OR 8.43), and increase in spleen size (≥ 30%; OR 6.01) were significant risk factors for collateral vessel development. Multivariate analysis after stepwise selection revealed that the FIB-4 index and spleen size were significant independent predictive factors. A ≥ 1.76 increase in the FIB-4 index and a ≥ 30% increase in spleen size after 6months of oxaliplatin-based chemotherapy were significant predictive markers for collateral vessel development.

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.

Three Versus Six Months of Adjuvant Doublet Chemotherapy for Patients With Colorectal Cancer: A Multi-Country Cost-Effectiveness and Budget Impact Analysis

BackgroundThe Short Course Oncology Treatment (SCOT) trial demonstrated non-inferiority, less toxicity, and cost-effectiveness from a UK perspective of 3 versus 6 months of oxaliplatin-based chemotherapy for patients with colorectal cancer. This study assessed the cost-effectiveness of shorter treatment and the budget impact of implementing trial findings from the perspectives of all countries recruited to SCOT: Australia, Denmark, New Zealand, Spain, Sweden, and the United Kingdom. Patients and MethodsIndividual cost–utility analyses were performed from the perspective of each country. Resource, quality of life, and survival estimates from the SCOT trial (N = 6065) were used. Probabilistic sensitivity analysis and subgroup analyses were undertaken. Using undiscounted costs from these cost–utility analyses, the impact on country-specific healthcare budgets of implementing the SCOT trial findings was calculated over a 5-year period. The currency used was US dollars (US$), and 2019 was the base year. One-way and scenario sensitivity analysis addressed uncertainty within the budget impact analysis. ResultsThree months of treatment were cost saving and cost-effective compared to 6 months from the perspective of all countries. The incremental net monetary benefit per patient ranged from US$8972 (Spain) to US$13,884 (Denmark). The healthcare budget impact over 5 years for the base-case scenario ranged from US$3.6 million (New Zealand) to US$61.4 million (UK) and totaled over US$150 million across all countries. ConclusionThis study has widened the transferability of results from the SCOT trial, showing that shorter treatment is cost-effective from a multi-country perspective. The vast savings from implementation could fully justify the investment in conducting the SCOT trial.

Predictive Impact of Mucinous Tumors on the Clinical Outcome in Patients with Poorly Differentiated, Stage II Colon Cancer: A TOSCA Subgroup Analysis

Although American Society of Clinical Oncology and European Society for Medical Oncology guidelines have identified the negative prognostic factors that clinicians have to consider when treating their patients with stage II colon cancer (CC), the role of histological subtype is controversial. The randomized, multicenter, phase III TOSCA trial compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy in 3,759 patients with high-risk stage II or stage III CC. The objective of this substudy was to evaluate the influence of histological subtypes on the impact of the treatment duration of adjuvant chemotherapy in terms of relapse-free survival (RFS) and overall survival (OS) in 85 mucinous adenocarcinoma (MUC) and 389 nonmucinous adenocarcinoma (NMUC) patients with high-risk stage II, grade 3 CC. A significant interaction between treatment duration and histology was observed in both RFS (p = .027) and OS (p = .017). In the subgroup of patients with MUC, worse RFS (adjusted hazard ratio [HR], 3.95; 95% confidence interval [CI], 1.03-15.17; p = .045) and OS (HR, 9.56; 95% CI, 1.14-79.98; p = .037) were detected for patients treated in the 3-month arm. No statistically significant differences were found in the subgroup of patients with NMUC. Patients with MUC, grade 3, stage II CC require special attention and may need 6 months of oxaliplatin-based chemotherapy. Larger studies are required to assess the combined use of histology and other prognostic/predictive factors to define the administration of chemotherapy in patients with stage II CC and to improve their prognosis. Although ASCO and ESMO guidelines define the prognostic factors for patients with stage II colon cancer to establish the use of adjuvant chemotherapy, the influence of histological subtypes is controversial in this population. This study underscores that patients with grade 3 mucinous adenocarcinomas may need adjuvant chemotherapy with oxaliplatin and fluoropyrimidines for a duration of 6 months rather than 3 months.

551P - Clinical impact of mucinous and poorly differentiated tumours on the outcome of patients with stage II colon cancer: A TOSCA subgroup analysis

BackgroundASCO and ESMO guidelines have identified inadequate sampling of lymph nodes, pT4 primary tumors, obstruction or perforation, lymphovascular and perineural invasion, and poorly differentiated tumors as negative prognostic factors supporting the clinicians in treating their patients with stage II colon cancer (CC). However, the influence of histological subtypes on the risk of death or disease recurrence remains controversial. MethodsThe phase III, multicenter, randomized TOSCA trial compared 3 vs. 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy in 3,759 patients with high-risk stage II or stage III CC. Objective of this sub-study was to investigate the role of the histological subtype [(mucinous adenocarcinoma (MUC) or non-mucinous adenocarcinoma (NMUC)] on the impact of the treatment duration in terms of relapse-free survival (RFS) and overall survival (OS) in the subgroup of patients with high-risk stage II, grade 3CC. ResultsOut of 3,614 patients from 130 centres enrolled in the per-protocol population defined in the TOSCA trial, 85 MUC and 389 NMUC patients were included in this analysis. No statistical differences were found between 3 vs. 6 months groups in both histological subgroups in terms of baseline characteristics, except for tumor side. The proportion of patients with right-sided cancer was higher for patients with MUC than NMUC. A significant interaction between treatment duration and histology was observed on both RFS (p=0.027) and OS (p=0.017). In the subgroup of patients with MUC, worse RFS (adjusted hazard ratio [HR], 3.95; 95% confidence interval [CI], 1.03–15.17; p=0.045) and OS (HR, 9.56; 95% CI, 1.14–79.98; p=0.037) were detected for patients treated in the 3 months arm. No statistically significant differences were detected in the subgroup of patients with NMUC. ConclusionsBoth MUC and poorly differentiated subtypes have unfavorable clinical characteristics. Patients with MUC, grade 3, stage II CC require special attention and may need 6 months of oxaliplatin-based chemotherapy. Larger studies are required to clarify the possible negative effect of the histological subtype to improve the prognosis of these patients. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer: ASCO Clinical Practice Guideline.

To develop recommendations for duration of adjuvant chemotherapy with a fluoropyrimidine and oxaliplatin for patients with completely resected stage III colon cancer based on the results of trials of 3 months compared with 6 months of treatment. ASCO convened an Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel. Pooled data from the six International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Collaboration randomized controlled trials comprise the evidence base for these guideline recommendations. The recommendations for therapy duration apply to patients with completely resected stage III colon cancer who are being offered adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine. Recommendations are informed by the findings of a recent pooled analysis of clinical trials that compared 6 months versus 3 months of oxaliplatin-based chemotherapy. For patients at a high risk of recurrence (T4 and/or N2), adjuvant chemotherapy should be offered for a duration of 6 months. For patients at a low risk of recurrence (T1, T2, or T3 and N1), either 6 months of adjuvant chemotherapy or a shorter duration of 3 months may be offered on the basis of a potential reduction in adverse events and no significant difference in disease-free survival with the 3-month regimen. In determining duration of therapy, the Expert Panel recommends a shared decision-making approach, taking into account patient characteristics, values and preferences, and other factors and including a discussion of the potential for benefit and risks of harm associated with treatment duration. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .