A randomised phase III intergroup trial comparing high-dose infusional 5-fluorouracil with or without folinic acid with standard bolus 5-fluorouracil/folinic acid in the adjuvant treatment of stage III colon cancer: The Pan-European Trial in Adjuvant Colon Cancer 2 study

2013 ◽  
Vol 49 (8) ◽  
pp. 1868-1875 ◽  
Author(s):  
Claus-Henning Köhne ◽  
Laurent Bedenne ◽  
Alfredo Carrato ◽  
Olivier Bouché ◽  
Ivan Popov ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Folinic Acid ◽  
Adjuvant Treatment ◽  
Phase Iii ◽  
Stage Iii ◽  
High Dose ◽  
Stage Iii Colon Cancer ◽  
Intergroup Trial ◽  
European Trial

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 capecitabine treatment for stage III colon cancer in Japanese patients (KSCC0803).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 571-571
Author(s):  
M. Kitazono ◽  
Y. Emi ◽  
Y. Kakeji ◽  
Y. Sakaguchi ◽  
H. Samura ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
Adjuvant Treatment ◽  
Japanese Patients ◽  
Phase Iii ◽  
Stage Iii ◽  
Completion Rates ◽  
Clinical Trial Registry ◽  
D2 Lymph Node Dissection ◽  
Stage Iii Colon Cancer

571 Background: Capecitabine was approved in Japan in 2007 for the adjuvant treatment of stage III colon cancer based on Japanese clinical trial data in advanced and recurrent colorectal and breast cancers as well as data from the Phase III X-ACT trial. For the current study, we aimed to clarify compliance and tolerability of adjuvant treatment with capecitabine in Japanese patients. The study was entered in the UMIN clinical trial registry (UMIN000001444) by the Kyushu Study Group of Clinical Cancer (KSCC). Ethical approval was granted by the institutional review board of each hospital involved. Methods: Based on completion rates from the X-ACT trial we enrolled 97 patients with R0 stage III colon cancer who had histologically confirmed disease and had undergone curative resection (3D2 lymph node dissection). Patients were given oral capecitabine therapy (2,500 mg/m2/day; days 1–14 q3w; eight cycles) within 8 weeks of surgery. The proportion of patients completing eight cycles of treatment per protocol was the primary endpoint, and adverse event (AE) rate was analyzed as a secondary endpoint. Results: Treatment completion in the total patient population was 66.0% (64/97 patients; 95% CI: 55.7–75.3%) and in the per protocol population (PPP) was 70.3% (64/91; 95% CI: 59.8–79.5%). AEs leading to treatment discontinuation included hand-foot syndrome (HFS; n=7), hematotoxicity (n=5) and increased hepatic activity (n=4). Grade 3/4 AEs of note included HFS (22.7%), neutropenia (7.2%), diarrhea (2.1%), and increased bilirubin (0.0%). Of note, any treatment delay >3 weeks in the current trial was considered a withdrawal. In the X-ACT trial, delays of any duration were permitted. Using the X-ACT criteria the completion rate for the PPP in this study was 80.2%, comparable to the figure reported in X-ACT. Conclusions: Our results confirm those of previous global phase III studies and show that capecitabine is well tolerated in both global and Japanese-only populations, with similar high completion rates in both. [Table: see text]

Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study

The Lancet ◽  
2002 ◽  
Vol 360 (9334) ◽  
pp. 671-677 ◽  
Author(s):  
Cornelis JA Punt ◽  
Attila Nagy ◽  
Jean-Yves Douillard ◽  
Arie Figer ◽  
Torben Skovsgaard ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Folinic Acid ◽  
Adjuvant Treatment ◽  
Stage Iii ◽  
Randomised Study ◽  
Stage Iii Colon Cancer

Survival impact of CAPOX versus FOLFOX in the adjuvant treatment of stage III colon cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 710-710
Author(s):  
Jonathan M. Loree ◽  
Aaron Sha ◽  
Maryam Soleimani ◽  
Maria Yi Ho ◽  
Hagen F. Kennecke ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Treatment ◽  
Dose Intensity ◽  
Phase Iii ◽  
Stage Iii ◽  
Rank Test ◽  
Cox Models ◽  
Stage Iii Colon Cancer ◽  
T Stage ◽  
N Stage

710 Background: CAPOX and FOLFOX are used interchangeably in the adjuvant treatment of colon cancer despite the lack of comparative phase III trials.We aimed to compare toxicities, relative dose intensity (RDI), disease free (DFS) and overall survival (OS) of these regimens in the real world. Methods: We identified consecutively treated patients (pts) with stage III colon cancer at two centers who received either CAPOX or mFOLFOX6 when either option was accessible to pts. RDI was defined as total dose received divided by the total intended dose if all cycles had been delivered. Dose limiting toxicities (DLTs) were toxicities that resulted in a dose reduction of an agent. Survival was compared with the log-rank test and Cox models that adjusted for age, gender, ECOG, T-stage, and N-stage. Results: Of 394 pts, 61.7% received FOLFOX. Age, gender, ECOG, T-stage, N-stage, and time between surgery and start of therapy did not differ between groups. However, RDI and toxicity profiles differed between treatment groups (see Table). With a median follow up of 45 months, there was no difference in OS (HR 0.73, 95%CI 0.45-1.22; P= 0.24); however, CAPOX was associated with a more favorable DFS (HR 0.61, 95% CI 0.40-0.93; P= 0.022). In multivariate analysis, treatment with CAPOX showed trends towards improved OS (HR 0.61, 95% CI 0.34-1.07; P= 0.086). A significant association with improved DFS (HR 0.53, 95% CI 0.33-0.87; P= 0.012) persisted. Exploratory analysis comparing outcomes stratified by the presence of any DLT, neutropenia, thrombocytopenia, and neuropathy failed to show an association with either OS or DFS. (See table.) Conclusions: Our findings suggest that the use of adjuvant CAPOX is associated with an improved DFS despite greater toxicity and lower RDI. Patient selection, the higher starting dose of oxaliplatin in CAPOX, or the metronomic nature of capecitabine may be contributing to improved efficacy of CAPOX. [Table: see text]

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.

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