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 safety findings from a randomized phase III trial of capecitabine + oxaliplatin (XELOX) vs. bolus 5-FU/LV as adjuvant therapy for patients (pts) with stage III colon cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3569-3569 ◽  
Author(s):  
H. J. Schmoll ◽  
J. Tabernero ◽  
M. Nowacki ◽  
J. Maroun ◽  
T. Price ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Safety Data ◽  
Disease Free Survival ◽  
Skin Toxicity ◽  
Phase Iii ◽  
Stage Iii ◽  
Standard Regimen ◽  
Stage Iii Colon Cancer ◽  
Grade 3

3569 Background: Adjuvant capecitabine results in at least equivalent disease-free survival (DFS) to i.v. bolus 5-FU/LV in stage III colon cancer [Twelves et al. 2005]. Early phase III data in 1st-line metastatic colorectal cancer suggest that XELOX is as safe as oxaliplatin + infusional 5-FU ± LV [Sastre et al. 2005; Ducreux et al. 2005]. The XELOXA study compared safety and efficacy of XELOX vs. bolus 5-FU/LV (the standard regimen at study start) as adjuvant therapy for stage III colon cancer. Methods: Pts with resected disease were randomized to receive either XELOX (capecitabine 1000 mg/m2 bid d1–14 + oxaliplatin 130 mg/m2 d1, q3w for 8 cycles) or i.v. bolus 5-FU/LV (Mayo Clinic, LV 20 mg/m2 + 5-FU 425 mg/m2 d1–5, q4w for 6 cycles; or Roswell Park [RP], LV 500 mg/m2 + 5-FU 500 mg/m2 d1, w1–6 in 8w cycles x4). Centers’ preferred 5-FU/LV regimen was selected at study start and used in all pts. Results: 1861/1886 pts randomized between Apr 03 and Oct 04 are evaluable for safety. The rate of related grade 3/4 adverse events (AEs) was 54% for XELOX and 45% for 5-FU/LV ( table ). 60-day all cause mortality was 1.0% in both arms. Treatment-related death rate within 28 days from last dose was 0.7% for XELOX and 0.5% for 5-FU/LV. Conclusions: XELOX causes less myelosuppression and stomatitis but more skin toxicity than 5-FU/LV. The inclusion of oxaliplatin adds neurosensory toxicity. Cross-study comparison of grade 3/4 AEs in the current and MOSAIC trials suggests that XELOX safety is similar to FOLFOX4, with the advantage of an oral fluoropyrimidine-based regimen. Final safety data will be presented at the meeting, and efficacy data will be available in 2007. [Table: see text] [Table: see text]

Safety analysis of FOLFOX as adjuvant chemotherapy for stage III colon cancer in phase II study (NORTH/HGCSG1003): Detailed analysis of peripheral sensory neuropathy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 701-701
Author(s):  
Susumu Sogabe ◽  
Satoshi Yuki ◽  
Hiraku Fukushima ◽  
Norihiko Takahashi ◽  
Toshiaki Shichinohe ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Sensory Neuropathy ◽  
Japanese Patients ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Grade 3 ◽  
Resected Stage

701 Background: Oxaliplatin-containing regimen is a standard adjuvant chemotherapy for resected stage III colon cancer. Oxaliplatin-containing regimens were investigated for their efficacy in patients with resected stage III colon cancer in MOSAIC and XELOXA studies. Since these two international randomized studies were performed outside of Japan, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy in Japanese patients (pts) with resected stage III colon cancer (UMIN ID: 000004590). Methods: This phase II study enrolled patients with resected stage III colon cancer. Patients received 12 biweekly cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was DFS. Secondary endpoints included overall survival (OS) and safety. Results: From September 2010 to March 2013, 273 pts were enrolled at 28 institutions. Safety analysis included 265 patients who received FOLFOX. Patients characteristics were as follows: median age, 65 (33-84); male/female: 131/134; PS 0/1:258/7; stage IIIA/IIIB/IIIC: 37/197/31; colon/rectosigmoid: 214/51. The most common grade 3-4 adverse events were neutrophil count decreased (48.1%), platelet count decreased (2.3%), and allergic reaction (1.5%). The incidence of peripheral sensory neuropathy (PSN) was 41.9% (grade 1), 38.1% (grade 2), and 6.4% (grade 3). PSN tended to be serious depending on the cumulative dose of oxaliplatin (table 1). Median cumulative dose of oxaliplatin at which PSN occurred were as follows: grade 1; 170 mg/m2, ≥ grade 2; 850 mg/m2, ≥ grade 3; (-). The median number of cycles of chemotherapy was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. Conclusions: In Japanese patients with stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. Clinical trial information: 000004590. [Table: see text]

Baseline creatinine clearance as an indicator of severe adverse events associated with oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer: Safety analysis of the phase III Japanese ACHIEVE trial.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 667-667
Author(s):  
Masato Nakamura ◽  
Masahito Kotaka ◽  
Tetsuya Eto ◽  
Dai Manaka ◽  
Junichi Hasegawa ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adverse Events ◽  
Creatinine Clearance ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Baseline Creatinine ◽  
Grade 3

667 Background: The phase III ACHIEVE trial (JFMC47), a project of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA), was established to prospectively analyze data from several randomized trials to test whether 3-month (arm 3) oxaliplatin-based adjuvant (FOLFOX4, mFOLFOX6, or XELOX) treatment is non-inferior to 6-month (arm 6) treatment in terms of disease-free survival in patients (pts) with stage III colon cancer. It aims to reveal the association between baseline characteristics and ≥ grade 3 adverse events (AEs) related to XELOX and mFOLFOX6, particularly focusing on the role of baseline creatinine clearance (CCr) on ≥ grade 3 AEs. Methods: This association was assessed using the Cox proportional hazards model. Results: During 2012–2014, 1,313 pts were randomized from 244 centers; 1,301 were included in the intention-to-treat population. Among the safety population (N = 1,277; 642, arm 3; 635, arm 6), the overall incidence of ≥ grade 3 AEs was 29% in arm 3 and 43% in arm 6 (p < 0.0001). Neuropathy of ≥ grade 2 was more frequent in arm 6 than in arm 3 (37% vs. 14%; p < 0.0001). Regarding the fluoropyrimidine backbone, grade 3–4 neutropenia was more with mFOLFOX6 than XELOX (30% vs. 12%), whereas grade 3–4 anorexia (2% vs. 5%) and grade 3–4 diarrhea (1% vs. 6%) were more with XELOX. Multivariate analysis, including treatment duration, regimen, CCr ( < 50 vs. > 50 mL/min), age, and sex, showed that CCr had a statistically significant impact on the occurrence of ≥ grade 3 AEs (hazard ratio = 0.44, p < 0.0001). Pts with CCr < 50 may have had more frequent ≥ grade 3 AEs independent of other factors, such as age. Conclusions: Grade 3 or higher AEs related to XELOX or mFOLFOX6 may be associated with the degree of CCr. Clinical trial information: UMIN 000008543.

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.

Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial

2018 ◽  
Vol 36 (15) ◽  
pp. 1469-1477 ◽  
Author(s):  
Thierry André ◽  
Dewi Vernerey ◽  
Laurent Mineur ◽  
Jaafar Bennouna ◽  
Jérôme Desrame ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Health Care Providers ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Care Providers ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

Sign in / Sign up

Export Citation Format

Share Document