North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer (NORTH/HGCSG1003).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 807-807
Author(s):  
Toshiaki Shichinohe ◽  
Satoshi Yuki ◽  
Norihiko Takahashi ◽  
Hiroshi Nakatsumi ◽  
Yasuyuki Kawamoto ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Disease Free Survival ◽  
Japanese Patients ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Resected Stage

807 Background: FOLFOX and XELOX are standard adjuvant chemotherapy for resected stage III colon cancer. MOSAIC and XELOXA trials were performed outside of Japan, thus, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy for 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 cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was disease-free survival (DFS). We assumed an expected 3-year DFS rate of 81.2% in this study. Secondary endpoints included overall survival (OS) and safety. In this meeting, we present for the 3-year DFS rate. Results: From Sep 2010 to Mar 2013, 273 pts were enrolled at 28 institutions. Full 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%), peripheral sensory neuropathy (6.4%), platelet count decreased (2.3%), and allergic reaction (1.5%). The median number of cycles of FOLFOX was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. The 3-year DFS rate was 75.2 percent (95% confidence interval, 69.6 to 80.0). Conclusions: In Japanese patients with stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. In this trial, the 3-year DFS rate of primary endpoint was not meet the expectation (81.2%). However, the 3-year DFS rate in this trial was similar to several pivotal trials. We plan to do subset analysis. Clinical trial information: UMIN000004590.

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]

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

2019 ◽  
Vol 37 (16) ◽  
pp. 1436-1447 ◽  
Author(s):  
Christopher Lieu ◽  
Erin B. Kennedy ◽  
Emily Bergsland ◽  
Jordan Berlin ◽  
Thomas J. George ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Expert Panel ◽  
Disease Free Survival ◽  
Evidence Base ◽  
Stage Iii ◽  
Risk Of Recurrence ◽  
Stage Iii Colon Cancer ◽  
Significant Difference ◽  
Resected Stage

PURPOSE 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. METHODS 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. RESULTS Pooled data from the six International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Collaboration randomized controlled trials comprise the evidence base for these guideline recommendations. 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 .

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.

Fluorouracil Plus Leucovorin as Effective Adjuvant Chemotherapy in Curatively Resected Stage III Colon Cancer: Results of the Trial adjCCA-01

2001 ◽  
Vol 19 (6) ◽  
pp. 1787-1794 ◽  
Author(s):  
Rainer Porschen ◽  
Andreas Bermann ◽  
Thomas Löffler ◽  
Gregor Haack ◽  
Klaus Rettig ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Postoperative Treatment ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Resected Stage ◽  
Disease Free

PURPOSE: Adjuvant postoperative treatment with fluorouracil (5-FU) and levamisole in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrence and improves survival. Biochemical modulation of 5-FU with leucovorin has resulted in increased remission rates in metastatic colorectal cancer, thus reflecting an increased tumor-cell kill. The impact of 5-FU plus leucovorin on survival and tumor recurrence was analyzed in comparison with the effects of 5-FU plus levamisole in the prospective multicentric trial adjCCA-01. PATIENTS AND METHODS: Patients with a curatively resected International Union Against Cancer stage III colon cancer were stratified according to T, N, and G category and randomly assigned to receive one of the two adjuvant treatment schemes: 5-FU 400 mg/m2 body-surface area intravenously in the first chemotherapy course, then 450 mg/m2 × 5 days; 12 cycles, plus leucovorin 100 mg/m2 (arm A), or 5-FU plus levamisole (Moertel scheme; arm B). RESULTS: Six hundred eighty (96.9%) of 702 patients enrolled onto this study were eligible. After a median follow-up time of 46.5 months, the 5-FU plus leucovorin combination significantly improved disease-free survival (P = .037) and significantly decreased overall mortality (P = .0089) in comparison with 5-FU plus levamisole. In a multivariate proportional hazards model, adjuvant chemotherapy emerged as a significant prognostic factor for survival (P = .0059) and disease-free survival (P = .03). Adjuvant treatment with 5-FU plus levamisole as well as with 5-FU plus leucovorin was generally well tolerated; only a minority of patients experienced grade 3 and 4 toxicities. CONCLUSION: After a curative resection of a stage III colon cancer, adjuvant treatment with 5-FU plus leucovorin is generally well tolerated and significantly more effective than 5-FU plus levamisole in reducing tumor relapse and improving survival.

Influence of KRAS mutations on outcome in patients with curatively resected stage III colon cancer treated with adjuvant chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14536-e14536
Author(s):  
Piercarlo Saletti ◽  
Martina Nucifora ◽  
Sara De Dosso ◽  
Alessandra Spitale ◽  
Nora Sahnane ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Single Agent ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Treatment Modalities ◽  
Rank Test ◽  
Kras Mutations ◽  
Stage Iii Colon Cancer ◽  
Resected Stage

e14536 Background: Adjuvant chemotherapy improves survival in patients with stage III colon cancer (CC) after curative resection, and oxaliplatin in combination with fluoropyrimidine-based regimens has been established as a standard treatment. KRAS mutations could predict oxaliplatin sensitivity in CC cells, as recently demonstrated. Here, we profiled KRAS and correlated it with outcome in stage III CC patients who underwent adjuvant chemotherapy. Methods: Eligible patients were those with resected stage III CC who underwent 6-months adjuvant chemotherapy, either with single-agent fluoropyrimidine (FP: modulated 5FU or capecitabine) or with oxaliplatin-based regimens (O-FP: FOLFOX or XELOX). DNA extraction was performed on formalin-fixed paraffin-embedded sections, and KRAS mutations were analyzed by direct sequencing. Disease-free survival (DFS) and overall survival (OS) analyses were computed using the Kaplan-Meier method and the Log-rank test. Results: The study population included 261 patients: 115 treated with FP, 146 O-FP. We identified KRAS mutations in 71/261 (27.4%) cases, of which 33 (46.5%) received FP, and 38 (53.5%) O-FP. In wild-type (wt) KRAS cases, DFS and OS group did not significantly differ between the two treatment modalities [in months, FP vs O-FP - median OS: 62.0 vs 49.6, HR: 1.12 (95% CI: 0.65; 1.92); median DFS: 57.1 vs 44.4, HR: 0.93 (95% CI: 0.55; 1.56)]. In patients treated with FP, a worse DFS [in months, mutant vs wt - median DFS: 46.0 vs 57.1, p=0.04; HR: 1.86 (95% CI: 1.01; 3.41)] and a trend toward a worse OS in months, mutant vs wt - median OS: 56.1 vs 62.0, p=0.08; HR: 1.71 (95% CI: 0.94; 3.10)] were observed in KRAS mutated patients. On the contrary, DFS and OS were not statistically different for mutated and wt KRAS patients treated with O-FP [in months, mutant vs wt - median DFS: 43.7 vs 44.4, p=0.62; HR: 1.17 (95% CI: 0.63; 2.18); median OS: 48.9 vs 49.6, p=0.77; HR: 1.11 (95% CI: 0.55; 2.23). Conclusions: Our results suggest that curatively resected stage III CC patients exhibiting wt KRAS status might benefit from FP alone. On the contrary, an oxaliplatin-containing regimen should be recommended in KRAS mutated patients.

scholarly journals Safety Analysis of Folfox as Adjuvant Chemotherapy for Stage III Colon Cancer in North Japan Multicenter Phase II Study (NORTH/HGCSG1003)

2014 ◽  
Vol 25 ◽  
pp. ii95
Author(s):  
Takahashi Norihiko ◽  
Yuki Satoshi ◽  
Fukushima Hiraku ◽  
Shichinohe Toshiaki ◽  
Sasaki Takahide ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Safety Analysis ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Multicenter Phase

A Japanese multicenter phase II study of adjuvant chemotherapy with mFOLFOX6/CAPOX for stage III colon cancer treatment after D2/D3 lymphadenectomy

Surgery Today ◽  
2019 ◽  
Vol 49 (6) ◽  
pp. 498-506 ◽  
Author(s):  
Kazuhiko Yoshimatsu ◽  
Keiichiro Ishibashi ◽  
Keiji Koda ◽  
Hajime Yokomizo ◽  
Noritaka Oda ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Treatment ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Stage Iii ◽  
D3 Lymphadenectomy ◽  
Stage Iii Colon Cancer ◽  
Multicenter Phase
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