scholarly journals S-1 and Oxaliplatin Versus Tegafur-uracil and Leucovorin as Postoperative Adjuvant Chemotherapy in Patients With High-risk Stage III Colon Cancer (ACTS-CC 02): A Randomized, Open-label, Multicenter, Phase III Superiority Trial

2020 ◽  
Vol 19 (1) ◽  
pp. 22-31.e6 ◽  
Author(s):  
Eiji Sunami ◽  
Tetsuya Kusumoto ◽  
Mitsuyoshi Ota ◽  
Yoshiyuki Sakamoto ◽  
Kazuhiro Yoshida ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Phase Iii ◽  
Stage Iii ◽  
Open Label ◽  
Postoperative Adjuvant Chemotherapy ◽  
Stage Iii Colon Cancer ◽  
Multicenter Phase ◽  
Superiority Trial

Preplanned initial safety analysis of ACTS-CC 02 trial: A large randomized phase III trial of SOX versus UFT/LV as adjuvant chemotherapy for high-risk stage III colon cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 572-572 ◽  
Author(s):  
Hiroya Takiuchi ◽  
Naohiro Tomita ◽  
Narikazu Boku ◽  
Toshiaki Watanabe ◽  
Kenjiro Kotake ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Adverse Events ◽  
Curative Resection ◽  
Phase Iii ◽  
Stage Iii ◽  
Postoperative Adjuvant Chemotherapy ◽  
Stage Iii Colon Cancer ◽  
To Receive

572 Background: The ACTS-CC 02 trial is designed to verify the superiority of postoperative adjuvant chemotherapy of S-1/Oxaliplatin (SOX) for patients with anyT, N2 colon cancer compared with UFT/Leucovorin (UFT/LV), which is one of standard adjuvant chemotherapies in Japan. To date, there have been no reported phase III trials evaluating SOX as postoperative adjuvant chemotherapy. This report presents initial safety data obtained from 50 patients who received SOX in the trial. Methods: Patients who underwent curative resection for anyT, N2 colon cancer were randomly assigned to receive either SOX (100 mg/m2 of oxaliplatin on day1, and 80 to 120 mg/day according to body surface area (BSA) of S-1 on days 1-14, every 21 days, 8 courses) or UFT/LV (300 to 600 mg/day according to BSA of UFT and 75 mg/day of LV on days 1-28, every 35 days, 5 courses). Data were collected from initial consecutive 50 patients assigned to the SOX group and analyzed when they were considered evaluable for safety as planned in the protocol. This ongoing trial is designed to accrue 1200 patients. As of September 15, 2011, 319 patients have been accrued. Results: Of 50 patients assigned to receive SOX, 48 were evaluable for safety. The median number of treatment courses was 5 (range: 1-8). The relative dose intensity of S-1 was 83.8% and that of oxaliplatin was 86.6%. Grade 3 adverse events were neutropenia (14.6%), thrombocytopenia (2.1%), ALT elevation (2.1%), diarrhea (8.3%), fatigue (2.1%), and peripheral sensory neuropathy (2.1%). Grade 4 adverse effects were not observed. Conclusions: In this initial safety analysis, the incidence and severity of adverse events with SOX were acceptable in patients with high risk stage III colon cancer after curative resection. Enrollment of patients is ongoing.

A randomized phase III trial of S-1/oxaliplatin (SOX) versus UFT/leucovorin as adjuvant chemotherapy for high-risk stage III colon cancer: The ACTS-CC 02 trial.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 484-484 ◽  
Author(s):  
Takao Takahashi ◽  
Eiji Sunami ◽  
Tetsuya Kusumoto ◽  
Mitsuyoshi Ota ◽  
Yoshiyuki Sakamoto ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Primary Endpoint ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Disease Stage ◽  
Stage Iiic ◽  
Stage Iii Colon Cancer

484 Background: The ACTS-CC 02 trial was designed to verify the superiority of postoperative adjuvant chemotherapy with S-1/oxaliplatin (SOX) over UFT/leucovorin (LV), one of the standard oral fluoropyrimidine regimens in Japan, in terms of disease-free survival (DFS) in patients (pts) with high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). The results of the safety analysis have been reported previously (Clin Colorectal Cancer, 2018). We now present the 3-year DFS results as the primary endpoint. Methods: Pts who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300–600 mg/day of UFT according to body surface area [BSA] and 75 mg/day of LV on days 1-28, every 35 days, 5 courses) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80–120 mg/day of S-1 according to BSA on days 1-14, every 21 days, 8 courses). The primary endpoint was DFS. Results: From April 2010 through October 2014, a total of 966 pts were enrolled at 260 institutions. The full analysis set, excluding pts who withdrew informed consent before protocol treatment, comprised 478 and 477 pts in the UFT/LV group and SOX group, respectively. The median age was 65.0 years. The ECOG PS was 0 in 94.0%, and the disease stage was IIIA/IIIB/IIIC in 1.3%/50.2%/48.6%. The 3-year DFS rate was 60.6% in the UFT/LV group and 62.7% in the SOX group (HR: 0.90; 95% CI: 0.74-1.09; p = 0.28); the superiority of SOX was not demonstrated. In stage IIIB, the 3-year DFS rate was 69.3% and 68.5% in the UFT/LV group and SOX group, respectively (HR: 1.01; 95% CI: 0.74-1.37; p = 0.95). In Stage IIIC, the 3-year DFS rate was 50.6% and 55.8% in the UFT/LV group and SOX group, respectively (HR: 0.82, 95% CI: 0.63-1.06; p = 0.12). Notably, in the N2b subgroup, the 3-year DFS rate was 46.0% and 54.7% in the UFT/LV group and SOX group, respectively (HR: 0.76, 95% CI: 0.55-1.05; p = 0.10). Conclusions: SOX was not shown to be superior to UFT/LV in pts with high-risk stage III colon cancer. However, the oxaliplatin-based regimen was suggested to be more effective in advanced disease, such as stage IIIC and N2b. Clinical trial information: JapicCTI-101073.

scholarly journals Safety data from the phase III Japanese ACHIEVE trial: part of an international, prospective, planned pooled analysis of six phase III trials comparing 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (3) ◽  
pp. e000354 ◽  
Author(s):  
Masahito Kotaka ◽  
Takeharu Yamanaka ◽  
Takayuki Yoshino ◽  
Dai Manaka ◽  
Tetsuya Eto ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Safety Data ◽  
Sensory Neuropathy ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Stage Iii ◽  
Open Label ◽  
Stage Iii Colon Cancer ◽  
Grade 3

BackgroundThe International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3).Patients and methodsACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator.ResultsBetween August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048).ConclusionsWe confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs.Trial registration numberUMIN000008543, Results.

Final results of the ACTS-CC 02 trial: A randomized phase III trial of S-1/oxaliplatin (SOX) versus UFT/leucovorin as adjuvant chemotherapy for high-risk stage III colon cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 59-59
Author(s):  
Naohiro Tomita ◽  
Shin Sasaki ◽  
Tetsuya Kusumoto ◽  
Jun Watanabe ◽  
Yoshiyuki Sakamoto ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Japanese Patients ◽  
Phase Iii ◽  
Stage Iii ◽  
Efficacy Analysis ◽  
Stage Iii Colon Cancer

59 Background: As previously reported (Sunami E, et al. Clin Colorectal Cancer. 2020), the ACTS-CC 02 trial demonstrated that S-1 and oxaliplatin (SOX) was not superior to UFT/leucovorin (LV) in terms of disease-free survival (DFS) as adjuvant chemotherapy for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). We now report the final overall survival (OS) after a median follow-up of more than 6 years. Methods: A total of 966 patients with high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300–600 mg/day of UFT according to body surface area [BSA] and 75 mg/day of LV on days 1-28, every 35 days, 5 courses) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80–120 mg/day of S-1 according to BSA on days 1-14, every 21 days, 8 courses). The primary endpoint was DFS. Patients’ data were updated in February 2020. Results: The subjects of this final efficacy analysis were 955 patients (478 in the UFT/LV group and 477 in the SOX group). Totally, Stage IIIA/IIIB/IIIC were 1.3%/50.2%/48.6% and T1/2/3/4 were 1.5%/4.0%/61.8%/32.7%. With median follow-up time of 74.3 months, the 5-year OS rate was 78.3% in the UFT/LV group and 79.1% in the SOX group (HR: 0.97; 95% CI: 0.76-1.24; p = 0.8175). The 5-year DFS rate was 55.2% in the UFT/LV group and 58.1% in the SOX group (HR: 0.92; 95% CI: 0.76-1.11; p = 0.3973). In an exploratory analysis, the 5-year OS rate in patients with T4 disease was 65.2% and 70.8% in the UFT/LV group and SOX group, respectively (HR: 0.81; 95% CI: 0.56-1.17), and the 5-year DFS rate was 45.4% and 50.5% (HR: 0.87; 95% CI: 0.65-1.19), respectively. Notably, in patients with T4N2b disease, the 5-year OS rate was 51.0% and 64.1% in the UFT/LV group and SOX group, (HR: 0.72; 95% CI: 0.40-1.31) and the 5-year DFS rate was 31.1% and 37.2% (HR: 0.87; 95% CI: 0.50-1.31), respectively. Conclusions: In Japanese patients with high-risk stage III colon cancer, the 5-year OS rate was similar in the UFT/LV group and SOX group. However, the oxaliplatin-based regimen was suggested to be more effective for DFS and OS in patients with advanced disease, such as T4N2b. Clinical trial information: JapicCTI-101073.

Clinical efficacy and safety of early adjuvant chemotherapy for stage III colon cancer: Short-term outcomes of a multicenter, randomized, open-label, phase 3 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3598-3598
Author(s):  
Jun Seok Park ◽  
Soo Yeun Park ◽  
Gyu-Seog Choi ◽  
Hye Jin Kim ◽  
Jong Gwang Kim ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adverse Events ◽  
Surgical Complication ◽  
Phase Iii ◽  
Stage Iii ◽  
Survival Outcomes ◽  
Stage Iii Colon Cancer

3598 Background: Adjuvant chemotherapy (AC) is recommended to commence within 8 weeks since after surgical resection of stage II or III colon cancer. Results of many retrospective studies showed inferior survival outcomes following delay of AC delay. Moreover, preclinical studies showed that the progression of disseminated cancer cells is profound during the postoperative period. This study is the first prospective trial to evaluate early (≤ 14 days postoperative) AC for patients (pts) with stage III colon cancer. Methods: This study is a prospective, multicenter, randomized phase III trial. Pts with pathological stage III colon cancer were enrolled and randomized 1:1 to early AC (starting AC ≤ 14 days after surgery) or conventional AC (starting AC > 14 days after surgery). Pts were recommended to receive 12 cycles of FOLFOX-6 for AC. The primary endpoint was disease-free survival. The secondary endpoints were overall survival, adverse events, surgical complication during AC, and patient-reported outcomes (quality of life) during 1 year after surgery. Herein, safety data, chemotherapy delivery, and quality of life are presented. Results: This study randomized 443 pts either early AC arm (221pts) or early AC arm (222 pts) to the during September 2011 to March 2020. 380 pts who received at least one cycle of FOLFOX-6 were included in the safety analysis (192 and 188 in the early and conventional AC arms, respectively). The baseline characteristics of the two groups were well-balanced except for the interval from the surgery to the initial AC. The early and conventional AC arms started their first chemotherapy at median of 13 (4-43 days) and 29 (17-53 days) after surgery (p < 0.001), respectively. No significant differences were seen in the median chemotherapy cycles, AC completion, and relative oxaliplatin dose intensity between groups. AC Completion without any change of dose or schedule delay was seen in 18% and 20% in early and conventional AC arms respectively, while dose reduction or delay was 65% and 61%, respectively. Toxicities of grade 3 or more were seen in 28% in both groups. One patient in the early AC arm underwent an emergent operation for anastomotic leakage on the second day of 5-fluorouracil infusion (postoperative day 14). However, the surgical complication was not seen in any other patient. The scores of the European Organization for Research and Treatment of Cancer Quality of Life core 30 questionnaire were similar in both arms at baseline (before starting AC), and 1 month, 3 months, 6 months, and 12 months after surgery. Conclusions: Early AC was safe and did not increase either chemotherapy-related adverse events or surgery-related complications during treatment. Moreover early AC did not reduce the quality of life of the pts during 1 year after surgery. This study continues to follow-up the patients for survival outcomes. Clinical trial information: NCT01460589.

Sign in / Sign up

Export Citation Format

Share Document