Adjuvant FOLFIRI with or without cetuximab in patients with resected stage III colon cancer: NCCTG Intergroup phase III trial N0147.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 363-363 ◽  
Author(s):  
J. Huang ◽  
D. J. Sargent ◽  
M. R. Mahoney ◽  
S. N. Thibodeau ◽  
T. C. Smyrk ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Clin Oncol ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Stage Iii Colon Cancer ◽  
Kras Status ◽  
Secondary Endpoints ◽  
Resected Stage

363 Background: Irinotecan (CPT-11) has demonstrated antitumor activity against metastatic colorectal cancer used alone or with 5-fluorouracil (5FU)/leucovorin (LV). Two arms with CPT-11, 5FU, and LV (FOLFIRI) +/- cetuximab (Cmab) were originally included in N0147. However, after CALGB 89803 (J Clin Oncol. 25:3456, 2007), PETACC-3 (J Clin Oncol. 27:3117, 2009), and Accord02 (Ann Oncol. 20:674, 2009) showed no benefit to the three-drug combination in adjuvant therapy, the CPT-11 arms of N0147 were discontinued. We report the outcomes for patients given FOLFIRI +/- Cmab. Methods: Following a signed informed consent patients with resected stage III colon cancer were randomized to one of 6 arms including 12 biweekly cycles of CPT-11 180 mg/m2 d1 with LV 400 mg/m2, 5FU 400 mg/m2 bolus IV, then 46-hr IV 5FU 2,400 mg/m2 on d1-2 without (Arm B, FOLFIRI) or with Cmab (Arm E) 400 mg/m2 d1 cycle 1 then Cmab at 250 mg/m2 d1 and 8. Primary endpoint was 3-year disease-free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Results: 156 patients (Arm B-111, Arm E-45) were enrolled; median follow-up on 81 patients in Arm B was 60.3 months and 58.2 months in Arm E for 41 patients. wtKRAS (vs mt) status was associated with improved DFS (HR=0.6 [95% CI 0.4-1.1], p = 0.09) and OS (HR 0.7 [95% CI 0.4-1.5], p = 0.38). The addition of Cmab improved DFS and OS in the overall group and within wtKRAS pts. Grade greater than III non-hematologic adverse effects were significantly increased in the Cmab arm (46% vs. 64%, p = 0.05). Conclusions: In this randomized phase III trial adjuvant FOLFIRI resulted in a 3-year DFS lower than that expected for FOLFOX. Trends for improved DFS and OS with the addition of Cmab were observed in patients with resected stage III colon cancer patients, regardless of KRAS status. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. [Table: see text] [Table: see text]

Adjuvant mFOLFOX6 with or without cetuxiumab (Cmab) in KRAS wild-type (WT) patients (pts) with resected stage III colon cancer (CC): Results from NCCTG Intergroup Phase III Trial N0147.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. CRA3507-CRA3507 ◽  
Author(s):  
S. R. Alberts ◽  
D. J. Sargent ◽  
T. C. Smyrk ◽  
A. F. Shields ◽  
E. Chan ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Kras Status ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Resected Stage

CRA3507 Background: FOLFOX is standard adjuvant therapy for stage III CC. Adding Cmab to FOLFOX benefits pts with metastatic CC WT KRAS tumors. N0147 assessed the potential benefit of Cmab added to FOLFOX. Methods: 21-56 days following resection and informed consent, KRAS status was centrally determined. Pts with wtKRAS CC were randomized to 12 biweekly cycles of oxaliplatin 85 mg/m2 d1, with leucovorin 400 mg/m2, 5FU 400 mg/m2 bolus IV, then 46-hr IV 5FU 2,400 mg/m2 on d1-2 (mFOLFOX6), without (arm A) or with Cmab (arm D) 250 mg/m2 d1&8, with Cmab at 400 mg/m2, cycle 1, d1. Primary endpoint was 3-yr disease free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Planned accrual of 2,070 wtKRAS pts provided 90% power to detect hazard ratio (HR) of 1.33 with 2-sided α=0.05; with interim analyses after 25%, 50%, and 75% of planned events. Results: 1,760 wtKRAS pts (Arm A-858, Arm D-902) were enrolled at the time of closure; median follow-up on 1,624 pts is 15.9 months. Trial closed to accrual when preplanned interim analysis after 50% of planned events demonstrated no benefit to addition of Cmab. 3-yr DFS favored FOLFOX alone (HR 1.18, 95% CI 0.92-1.52; p=0.33). No benefit of Cmab was observed in any subgroups assessed. Any grade ≥ 3 AE, diarrhea, and failure to complete 12 cycles was significantly increased in arm D. Increased toxicity and greater differences in all outcomes were observed in pts aged ≥ 70 ( Table ). Conclusions: In this randomized phase III trial the addition of Cmab to mFOLFOX6 was of no benefit for pts with resected stage III wtKRAS CC. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. [Table: see text] [Table: see text]

Six months versus twelve months of capecitabine as adjuvant chemotherapy for stage III (Dukes' C) colon cancer: Initial safety report for the open-label randomized phase III study (JFMC37-0801).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3607-3607 ◽  
Author(s):  
Katsuyuki Kunieda ◽  
Sotaro Sadahiro ◽  
Hideyuki Mishima ◽  
Chikuma Hamada ◽  
Shigetoyo Saji ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Treatment Duration ◽  
Disease Free Survival ◽  
Chemotherapeutic Agents ◽  
Phase Iii ◽  
Stage Iii ◽  
Serious Adverse Events ◽  
Phase Iii Trial ◽  
Stage Iii Colon Cancer

3607 Background: The standard treatment duration of adjuvant chemotherapy (CT) in patients (pts) with stage III colon cancer is 6 months. On the other hand, no clinical trial showed the optimal treatment duration of oral chemotherapeutic agents in adjuvant setting for colon cancer. Sargent et al have reported that 83% of recurrences in stage II and III pts have occurred within the first 3 years after surgery and peak was observed around one year after surgery. Therefore, to clarify the benefit of 12 months administration of Capecitabine, we designed randomized phase III trial for a comparison of 6 months treatment and 12 months treatment of capecitabine as adjuvant CT for stage III colon cancer. Methods: JFMC37 is a multicenter, randomized Phase III trial. Patients with fully resected Stage III colon or recto sigmoid cancer were eligible. Capecitabine was administered orally as tablets, 2,500 mg/m²/day for 14 days followed by a 7-days rest. Treatment is continued to 8 cycles (6 months) in arm A (A) or 16 cycles (12 months) in arm B (B). Patients were randomized 1:1 to A or B. Data size was estimated by disease free survival as primary endpoint. The statistical design is based on superiority hypothesis; 5-yrs DFS is 60% in arm A, 67% in arm B ;unilateral α=0.05, 1-β=0.8;and planed accrual is 1200 pts. Results: Between September 2008 to December 2009, 1304 patients were enrolled and then randomized. Both arms were well balanced for mean age: (A) 64.1, (B) 63.8; ECOG PS (%0/1): (A) 95.0/5.0, (B) 97.1/2.9; involvement of lymph nodes (%N0/N1/N2): (A) 77.1/19.9/3.1, (B) 76.6/19.7/3.7. Treatment completion rate for A and B were 68.2% and 43.4%. Incidences of serious adverse events (SAEs) over 1% were neutropenia: (A) 2.6%, (B) 3.8%, diarrhea: (A) 2.9%, (B) 2.1%, loss of appetite: (A) 1.3%, (B) 1.0%, fatigue: (A) 1.8%, (B) 1.2%, hand-hoot syndrome: (A) 16.4%, (B) 22.1%. Conclusions: There were no obvious differences in SAEs between arm A and arm B. Although twelve months of capecitabine showed a tendency to increase G3/4 hand-foot syndrome, we concluded that incidence of SAEs were acceptable and comparable to previously report.

Randomized Phase III Trial Comparing Biweekly Infusional Fluorouracil/Leucovorin Alone or With Irinotecan in the Adjuvant Treatment of Stage III Colon Cancer: PETACC-3

2009 ◽  
Vol 27 (19) ◽  
pp. 3117-3125 ◽  
Author(s):  
Eric Van Cutsem ◽  
Roberto Labianca ◽  
György Bodoky ◽  
Carlo Barone ◽  
Enrique Aranda ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Stage Iii ◽  
High Dose ◽  
Phase Iii Trial ◽  
Efficacy Analysis ◽  
Stage Iii Colon Cancer

PurposeThe primary objective of this randomized, multicenter, phase III trial was to investigate whether the addition of irinotecan to the de Gramont infusional fluorouracil (FU)/leucovorin (LV) adjuvant regimen (LV5FU2) would improve disease-free survival (DFS) in patients with stage III colon cancer.Patients and MethodsAfter curatively intentioned surgery, patients with stage II and III colon cancer were randomly allocated surgery to receive LV5FU2 (LV 200 mg/m2as a 2-hour infusion, followed by FU; as a 400 mg/m2bolus and then a 600 mg/m2continuous infusion over 22 hours, days 1 and 2, every 2 weeks for 12 cycles: de Gramont regimen) with or without irinotecan (180 mg/m2as a 30- to 90-minute infusion, day 1, every 2 weeks). In total, 260 (7.9%) of 3,278 patients received an alternative high-dose infusional FU/LV regimen (Arbeitsgemeinschaft Internische Onkologie regimen) with or without irinotecan.ResultsThe principal efficacy analysis was based on 2,094 treated patients with stage III disease, randomly allocated in the LV5FU2 strata. After a median follow-up of 66.3 months, the 5-year DFS rate was 56.7% with irinotecan/LV5FU2 and 54.3% with LV5FU2 alone (primary end point: log-rank P = .106). Combining irinotecan with LV5FU2 did not significantly improve overall survival in this patient group compared with LV5FU2 alone (5-year rate 73.6% v 71.3%, respectively; log-rank P = .094). The addition of irinotecan to LV5FU2 was associated with an increased incidence of grade 3 to 4 GI events and neutropenia.ConclusionIrinotecan added to LV5FU2 as adjuvant therapy did not confer a statistically significant improvement in DFS or overall survival in patients with stage III colon cancer compared with LV5FU2 alone.

Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial

2015 ◽  
Vol 33 (32) ◽  
pp. 3733-3740 ◽  
Author(s):  
Hans-Joachim Schmoll ◽  
Josep Tabernero ◽  
Jean Maroun ◽  
Filippo de Braud ◽  
Timothy Price ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Folinic Acid ◽  
Dihydropyrimidine Dehydrogenase ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Tumor Biomarker ◽  
Stage Iii Colon Cancer ◽  
Biomarker Analysis ◽  
Resected Stage

Purpose To report the final efficacy findings and biomarker analysis from the NO16968 trial comparing bolus fluorouracil/folinic acid (FU/FA) with capecitabine plus oxaliplatin (XELOX) in resected stage III colon cancer. Patients and Methods After curative resection, patients were randomly assigned to receive XELOX, as oxaliplatin 130 mg/m2 on day 1 and capecitabine 1,000 mg/m2 twice daily on days 1 to 14 every 3 weeks, or bolus FU/FA, as the Mayo Clinic or Roswell Park regimens, for 6 months. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS). Results The intention-to-treat population comprised 1,886 patients (XELOX, n = 944; FU/FA, n = 942). Seven-year DFS rates were 63% and 56% in the XELOX and FU/FA groups, respectively (hazard ratio [HR], 0.80; 95% CI, 0.69 to 0.93; P = .004). Seven-year OS rates were 73% and 67% in the XELOX and FU/FA groups, respectively (HR, 0.83; 95% CI, 0.70 to 0.99; P = .04). A total of 68% and 77% of patients who experienced relapse or a new colorectal cancer in the XELOX and FU/FA groups, respectively, received drug treatment for metastatic disease. Four hundred ninety-eight patients consented to the biomarker analysis: 242 in the XELOX group and 256 in the FU/FA group. Low tumor expression of dihydropyrimidine dehydrogenase may be predictive for XELOX efficacy; in the XELOX group, for high versus low dihydropyrimidine dehydrogenase expression levels, DFS HR was 2.45 (95% CI, 1.55 to 3.86; P < .001), and OS HR was 2.75 (95% CI, 1.65 to 4.59; P < .001). In the FU/FA group, no statistically significant associations were observed between any tumor biomarker and outcomes. Conclusion XELOX improved OS compared with bolus FU/FA in patients with resected stage III colon cancer after a median follow-up of almost 7 years. XELOX should be considered a standard adjuvant treatment option in patients with stage III disease. Tumoral dihydropyrimidine dehydrogenase expression is a promising predictive, and potentially, highly clinically relevant, biomarker for XELOX efficacy requiring further prospective evaluation.

Adjuvant mFOLFOX6 plus or minus cetuximab (Cmab) in patients (pts) with KRAS mutant (m) resected stage III colon cancer (CC): NCCTG Intergroup Phase III Trial N0147.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 3508-3508 ◽  
Author(s):  
R. M. Goldberg ◽  
D. J. Sargent ◽  
S. N. Thibodeau ◽  
M. R. Mahoney ◽  
A. F. Shields ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Stage Iii Colon Cancer ◽  
Resected Stage

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.

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 .

Sign in / Sign up

Export Citation Format

Share Document