A prospective randomized phase III trial of adjuvant chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with stage II colon cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4052-4052
Author(s):  
W. Schippinger ◽  
H. Samonigg ◽  
R. Greil ◽  
J. Tschmelitsch ◽  
G. Steger ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Primary Endpoint ◽  
Lower Risk ◽  
Stage Ii ◽  
Phase Iii ◽  
Disease Relapse ◽  
Chi Square ◽  
Significant Difference ◽  
Stage Ii Colon Cancer

4052 Background: Whereas several studies showed adjuvant chemotherapy to improve survival of patients with stage III colon cancer, survival benefit from adjuvant treatment in patients with stage II disease is a matter of controversy. Methods: Patients with curatively resected stage II colon cancer (T3–4, N0, M0) according to UICC were randomized to either adjuvant chemotherapy with 5-FU/LV (100 mg/m2 LV + 450 mg/m2 5-FU weekly, w 1–6, in 8 w cycles x 7) or surveillance only. Primary endpoint was overall survival (OS) with 636 patients originally planned to demonstrate a difference in OS of 10% with 85% power and alfa =0.05 in a final analysis 7 years after study initiation. After accrual of 535 patients between 11/1993 and 6/2003, recruitment was stopped ahead of schedule for low accrual rates. Results: 505 patients were eligible and evaluable for analyses. After a median follow-up of 96 months, 56 (21.8%) patients have died in the 5-FU/LV arm and 58 (23.4%) in the surveillance arm. There was no statistically significant difference in OS between the two treatment arms (HR 1.137, 95% CI 0.787–1.641, p=0.4947, chi square), thus the primary endpoint of the study was not met. Disease relapse was documented in 35 (13.6%) patients of the chemotherapy arm and in 48 (19.4%) patients of the control arm. The relative risk for disease relapse was higher for patients in the surveillance arm compared to patients in the 5-FU/LV arm, however, this difference was statistically not significant (HR 1.506, 95% CI 0.974–2.328, p=0.0657, chi square). Subgroup analysis including in the chemotherapy arm only patients who received at least one cycle of 5-FU/LV (n=250), showed a statistically significantly lower risk for relapse in patients treated with 5- FU/LV (HR 1.559, 95% CI 1.001–2.429, p=0.0477, chi square). Conclusions: Results of this trial demonstrate a trend to a lower risk for relapse in patients treated with adjuvant 5-FU/LV for stage II colon cancer. However, adjuvant chemotherapy did not significantly improve DFS and OS. No significant financial relationships to disclose.

scholarly journals Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial

2021 ◽  
Vol 32 (1) ◽  
pp. 77-84
Author(s):  
K. Yamazaki ◽  
T. Yamanaka ◽  
M. Shiozawa ◽  
D. Manaka ◽  
M. Kotaka ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Phase Iii ◽  
Stage Ii Colon Cancer

NRG-GI005 (COBRA): Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS261-TPS261
Author(s):  
Van K. Morris ◽  
Greg Yothers ◽  
Scott Kopetz ◽  
Samuel A. Jacobs ◽  
Peter C. Lucas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Phase Iii ◽  
Stage Ii Colon Cancer ◽  
Tumor Dna

TPS261 Background: There are currently no validated predictive biomarkers for stage II resected colon cancer (CC) after adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) that is shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells. For patients (pts) with CC, the detection of ctDNA is associated with persistent disease after resection and may outperform traditional clinical and pathological features as a prognostic factor to assess risk for recurrence. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N=1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for no adjuvant chemotherapy will be randomized 1:1 into 2 arms: standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the GuardantHealth LUNAR panel, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. Trial accrual is anticipated across all US and Canadian cooperative groups.NCT#: 04068103. Support: U10-CA-180868, -180822; UG1CA-189867; GuardantHealth. Clinical trial information: 04068103.

scholarly journals A prospective randomised phase III trial of adjuvant chemotherapy with 5-fluorouracil and leucovorin in patients with stage II colon cancer

2007 ◽  
Vol 97 (8) ◽  
pp. 1021-1027 ◽  
Author(s):  
W Schippinger ◽  
◽  
H Samonigg ◽  
R Schaberl-Moser ◽  
R Greil ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Stage Ii Colon Cancer

scholarly journals Study protocol of the SACURA trial: a randomized phase III trial of efficacy and safety of UFT as adjuvant chemotherapy for stage II colon cancer

BMC Cancer ◽  
2012 ◽  
Vol 12 (1) ◽  
Author(s):  
Megumi Ishiguro ◽  
Hidetaka Mochizuki ◽  
Naohiro Tomita ◽  
Yasuhiro Shimada ◽  
Keiichi Takahashi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Study Protocol ◽  
Stage Ii ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Phase Iii Trial ◽  
Stage Ii Colon Cancer

A randomized phase III trial of 1-year adjuvant chemotherapy with oral tegafur-uracil (UFT) vs. surgery alone in stage II colon cancer: SACURA trial.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 3617-3617 ◽  
Author(s):  
Yoshiki Kajiwara ◽  
Megumi Ishiguro ◽  
Satoshi Teramukai ◽  
Chu Matsuda ◽  
Shoichi Fujii ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Stage Ii Colon Cancer

Microsatellite instability and adjuvant chemotherapy in stage II colon cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 767-767
Author(s):  
Julie L. Koenig ◽  
Albert Y. Lin ◽  
Erqi L. Pollom ◽  
Daniel Tandel Chang
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Univariate Analysis ◽  
Population Based ◽  
Stage Ii ◽  
Chi Square ◽  
Colon Cancers ◽  
Multiple Characteristics ◽  
Stage Ii Colon Cancer

767 Background: Randomized control trials and population-based studies have not demonstrated a definitive benefit for adjuvant chemotherapy in stage II colon cancers. Tumor side and microsatellite instability (MSI) have been proposed as prognostic and predictive factors, but there is little consensus about their utility. Previous studies have been limited by the availability of MSI data. Because microsatellite stability (MSS) is associated with worse prognosis and higher risk of metastases, we hypothesized patients with MSS would have increased benefit from chemotherapy. Methods: Using the National Cancer Database, we preformed a retrospective cohort study of patients with resected stage II colon cancer diagnosed 2006-2013. Patient and disease characteristics were compared with chi-square tests. Survival was evaluated with Cox proportional hazard models. Results: We identified 59,475 patients with stage II colon cancer. 11.4% of patients had known MSI status (n = 6,763) of which 88% had MSS (n = 5,953) and 12% had MSI (n = 810). Patients with MSS were more likely to receive chemotherapy (28.2% vs 19.9%, p < 0.001) and have left-sided tumors (38.8% vs 16.7%, p < 0.001). MSI (adjusted hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.48-0.87; p = 0.003) and receipt of chemotherapy (HR 0.54, 95% CI 0.42-0.69; p < 0.001) were associated with better survival after controlling for multiple characteristics including tumor side. Although left-sided tumors had better survival on univariate analysis (HR 0.91, 95% CI 0.88-0.94; p < 0.001), side was not an independent predictor of survival after controlling for MSI and other characteristics (HR 1.01, 95% CI 0.86-1.20; p = 0.860). Among patients with MSS, chemotherapy remained associated with improved survival (HR 0.54, 95% CI 0.43-0.70; p < 0.001) and this benefit did not vary by tumor side (interaction p = 0.380). There was no interaction between MSI status and chemotherapy (p = 0.139), but we observed less of a survival benefit for chemotherapy in patients with MSI (HR 0.81, 95% CI 0.38-1.75; p = 0.595). Conclusions: Our data suggest a benefit for adjuvant chemotherapy in stage II colon cancer even after adjusting for MSI status. However, tumor side was not prognostic after controlling for MSI status.

Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4121-TPS4121
Author(s):  
Van K. Morris ◽  
Greg Yothers ◽  
Scott Kopetz ◽  
Samuel A. Jacobs ◽  
Peter C. Lucas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Phase Iii ◽  
Stage Ii Colon Cancer ◽  
Tumor Dna

TPS4121 Background: There are currently no validated predictive biomarkers for stage II resected colon cancer (CC) after adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) that is shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells. For patients (pts) with CC, the detection of ctDNA is associated with persistent disease after resection and may outperform traditional clinical and pathological features as a prognostic factor to assess risk for recurrence. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N=1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for no adjuvant chemotherapy will be randomized 1:1 into 2 arms: standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the GuardantHealth LUNAR panel, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. The trial is actively accruing towards the phase II endpoint across all US and Canadian cooperative groups. Support: U10-CA-180868, -180822; UG1CA-189867; GuardantHealth. Clinical trial information: NCT04068103 .

Phase II/III study of Circulating tumOr DNA as a predictive BiomaRker in Adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS3622-TPS3622
Author(s):  
Van K. Morris ◽  
Greg Yothers ◽  
Scott Kopetz ◽  
Samuel A. Jacobs ◽  
Peter C. Lucas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Phase Iii ◽  
Stage Ii Colon Cancer ◽  
Tumor Dna

TPS3622 Background: There are currently no validated predictive biomarkers for stage II resected colon cancer (CC) after adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) that is shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells. For patients (pts) with CC, the detection of ctDNA is associated with persistent disease after resection and may outperform traditional clinical and pathological features as a prognostic factor to assess risk for recurrence. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N = 1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for no adjuvant chemotherapy will be randomized 1:1 into 2 arms: standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the GuardantHealth LUNAR panel, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. The trial is actively accruing towards the phase II endpoint in North America. NCT#: 04068103. Support: U10-CA-180868, -180822; UG1CA-189867; GuardantHealth. Clinical trial information: NCT04068103.

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