Safety of UFT/LV and S-1 as adjuvant therapy for stage III colon cancer in phase III trial: ACTS-CC trial.
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ABSTRACT: Background
The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis.Methods
Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m(-2) per day as tegafur; LV, 75 mg per day on days 1-28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1-28, every 42 days, 4 courses). Treatment status and safety were evaluated.Results
Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of grade 3 AEs were 16% and 14%, respectively.Conclusion
Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.
SUBMITTER: Mochizuki I
PROVIDER: S-EPMC3314794 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Interventions: Group A (standard therapy group:UFT/LV 6M): Administration of 5 courses (6 months) of a schedule in which one course consists of UFT (300 mg/m2/day) and LV (75 mg/day) for 28 consecutive days followed by 7 days off the drugs.
Group B (trial therapy group: PSK/UFT/LV 6M): Administration of 5 courses (6 months) of a schedule in which one course consists of UFT (300 mg/m2/day) and LV (75 mg/day) for 28 consecutive days followed by 7 days off the drugs. And administration of every day PSK (3g/body) for 6 months.
Group C (trial therapy group: PSK/UFT/LV 12M): Administration of 10 courses (12 months) of a schedule in which one course consists of UFT (300 mg/m2/day) and LV (75 mg/day) for 28 consecutive days followed by 7 days off the drugs. And administration of every day PSK (3g/body) for 12 months.
Primary outcome(s): 3 year desease free survival rate
Study Design: Parallel Randomized
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Project description:BackgroundThe benefit of chemotherapy in colon cancer patients is well documented but depends largely on whether patients complete the planned treatment regimen. We evaluated predictors of early discontinuation (EDChemo) and dose reduction of chemotherapy, especially the role of adverse treatment effects, in stage III patients who received adjuvant chemotherapy.MethodsStage III colon cancer patients who were diagnosed in 2003-2014 and recruited into a population-based study in Germany and received FOLFOX [5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin], capecitabine monotherapy (CapMono), or 5-FU/LV were included. We assessed determinants of EDChemo and dose reduction using multivariable logistic regression. Also, we estimated proportions of EDChemo and dose reduction that are attributable to adverse effects using attributable fractions.ResultsEDChemo and dose reduction rates were 52% and 17% for FOLFOX, 28% and 9% for CapMono, and 45% and 6% for 5-FU/LV, respectively. Predictors of EDChemo were low-grade tumor and treatment in a medium-volume hospital (for FOLFOX), obesity (for CapMono), and increasing age, T4 stage, and treatment in a medium-volume hospital (for 5-FU/LV). Adverse effects were particularly strongly associated with EDChemo and contributed to about 63%, 51%, and 32% of EDChemo of FOLFOX, CapMono, and 5-FU/LV, respectively. Of the various adverse effects, gastrointestinal events showed the strongest associations with EDChemo and accounted for about 7%, 26%, and 20% of EDChemo of FOLFOX, CapMono, and 5-FU/LV, respectively. Adverse effects were, moreover, a strong determinant of dose reduction and accounted for about 82% of all cases.ConclusionsEDChemo is common in stage III colon cancer patients receiving chemotherapy and more than half of the cases of EDChemo and dose reduction are due to adverse treatment effects. Further research should address the potential for reducing EDChemo and dose reduction rates by close monitoring of patients for early signs and enhanced management of adverse effects, especially gastrointestinal events.
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Project description:PURPOSE:To determine the frequency and prognostic association of molecular markers by anatomic tumor site in patients with stage III colon carcinomas. EXPERIMENTAL DESIGN:In a randomized trial of adjuvant FOLFOX ± cetuximab, BRAF(V600E) and KRAS (exon 2) mutations and DNA mismatch repair (MMR) proteins were analyzed in tumors (N = 3,018) in relationship to tumor location, including subsite. Cox models were used to assess clinical outcome, including overall survival (OS). RESULTS:KRAS codon 12 mutations were most frequent at the splenic flexure and cecum; codon 13 mutations were evenly distributed. BRAF mutation frequency sharply increased from transverse colon to cecum in parallel with deficient (d) MMR. Nonmutated BRAF and KRAS tumors progressively decreased from sigmoid to transverse (all P < 0.0001). Significantly, poorer OS was found for mutant KRAS in distal [HR, 1.98; 95% confidence interval (CI), 1.49-2.63; P < 0.0001] versus proximal (1.25; 95% CI, 0.97-1.60; P = 0.079) cancers. BRAF status and outcome were not significantly associated with tumor site. Proximal versus distal dMMR tumors had significantly better outcome. An interaction test was significant for tumor site by KRAS (P(adjusted) = 0.043) and MMR (P(adjusted) = 0.010) for OS. Significant prognostic differences for biomarkers by tumor site were maintained in the FOLFOX arm. Tumor site was independently prognostic with a stepwise improvement from cecum to sigmoid (OS: P(adjusted) = 0.001). CONCLUSIONS:Mutation in BRAF or KRAS codon 12 was enriched in proximal cancers whereas nonmutated BRAF/KRAS was increased in distal tumors. Significant differences in outcome for KRAS mutations and dMMR were found by tumor site, indicating that their interpretation should occur in the context of tumor location.
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Project description:BACKGROUND:A fixed 8-cycle oxaliplatin and capecitabine (XELOX) regimen has been the standard adjuvant therapy for patients with stage III colon cancer. However, completing the full-cycle of oxaliplatin is often associated with severe neurotoxicity. To spare patients from the toxic effects, without comprising the required efficacy, we evaluated the safety and efficacy of a modified XELOX (mXELOX) adjuvant chemotherapy regimen with 6 cycles of oxaliplatin and a full cycle of capecitabine. METHODS:We retrospectively analyzed 330 eligible patients with stage III colon cancer who underwent curative tumor resection followed by mXELOX, standard XELOX or unfinished XELOX adjuvant chemotherapy between December 2007 and April 2015. Associated prognostic factors were investigated and their disease-free survival (DFS) and overall survival (OS) rates were also determined and compared among the different regimen groups. RESULTS:Compared with the standard XELOX group, the mXELOX group had lower total incidence rates of neurotoxicity (39.3% vs. 76.2%, P?<?0.001), leucopenia (53.6% vs. 69.8%, P?=?0.017) and thrombocytopenia (38.1% vs. 56.3%, P?=?0.011). The standard XELOX and mXELOX adjuvant chemotherapy regimens presented with comparable 3-year DFS rates (86.3% vs. 89.2%; P?=?0.838) and 3-year OS rates (92.7% vs. 97.6%; P?=?0.227). Compared to unfinished XELOX chemotherapy, the oncologic benefits of the mXELOX regimen were greater for patients with T4 tumors (3-year DFS: Hazard ratio [HR], 2.184; 95% confidence interval [CI], 1.051-4.540; P?=?0.036; 3-year OS: HR, 4.529; 95% CI 1.245-16.479; P?=?0.022) and for high-risk patients (3-year DFS: HR, 1.962; 95% CI 0.964-3.993; P?=?0.044; 3-year OS: HR, 4.193; 95% CI 1.182-14.874; P?=?0.026). CONCLUSIONS:The mXELOX adjuvant chemotherapy presented a comparable survival benefit and lower incidence of toxicity than standard XELOX chemotherapy. It could be an alternative treatment for high-risk patients with operated stage III colon cancer.
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