A novel interaction of genotype, gender, and adjuvant treatment in survival after resection of stage III colon cancer: Results of CALGB 89803.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 452-452
Author(s):  
Chloe Evelyn Atreya ◽  
Robert S. Warren ◽  
Donna Niedzwiecki ◽  
Robert J. Mayer ◽  
Richard M. Goldberg ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Phase Iii ◽  
Zinc Binding ◽  
Stage Iii ◽  
P53 Mutations ◽  
Stage Iii Colon Cancer ◽  
Mutational Status ◽  
The Impact

452 Background: The p53 tumor suppressor gene is frequently mutated in colorectal cancer, but reports on the effect of p53 mutations on response to adjuvant chemotherapy and survival are inconclusive. This study investigates whether p53 mutational status (wild-type, zinc or non-zinc binding mutations) impacts survival following adjuvant therapy containing fluorouracil/leucovorin with or without irinotecan (5FU/LV or IFL) in women and men with stage III colon cancer. Methods: As part of a retrospective analysis of prospectively accrued data, p53 mutational status was determined for 609 patients with stage III colon cancer who were randomized on CALGB 89803, a phase III adjuvant chemotherapy trial. p53 exons 5-8 were analyzed by direct sequencing or sequencing by hybridization. p53 mutations were identified in 276 tumors (45%), of which 134 were in the zinc binding and 142 were in the non-zinc binding regions of the core domain. Cox regression was used to study the impact of p53 mutational status, sex, and adjuvant chemotherapy on disease-free (DFS) and overall survival (OS). Results: p53 mutational status did not predict differential survival or response to adjuvant therapy among the 609 patients assessed. However, a significant sex by treatment interaction was observed for both DFS (Pinteraction=0.008) and OS (Pinteraction=0.002). Significant differences in DFS by p53 mutational status were observed among women (logrank P = 0.009). No such differences were observed among men (logrank P = 0.33). Similar results were observed for OS. There was marginal evidence of a treatment-related impact on the interaction between sex and p53 mutational status for both DFS and OS (DFS Pinteraction = 0.07; OS Pinteraction = 0.11). There was a trend toward improved OS when women with zinc binding mutations received IFL versus 5FU/LV (P = 0.08) and toward worse DFS when women with non-zinc binding mutations were treated with IFL versus 5FU/LV (P =0.08). Conclusions: This exploratory subset analysis suggests that p53 mutational status may be used to predict prognosis in a sex- and potentially chemotherapeutic regimen-specific manner.

Noninferiority of S-1 to UFT/LV as adjuvant chemotherapy for stage III colon cancer: A randomized phase III trial (ACTS-CC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3518-3518 ◽  
Author(s):  
Yoshihiko Nakamoto ◽  
Megumi Ishiguro ◽  
Motoki Yoshida ◽  
Koji Ikejiri ◽  
Izumi Mochizuki ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Completion Rate ◽  
Phase Iii ◽  
Stage Iii ◽  
Curative Surgery ◽  
Aged Patients ◽  
Phase Iii Trial ◽  
Stage Iii Colon Cancer

3518 Background: The ACTS-CC trial is a phase III trial designed to validate non-inferiority of S-1 to UFT/LV, a standard treatment in Japan as adjuvant chemotherapy for stage III colon cancer. This is the first report which evaluated the efficacy of S-1 as adjuvant therapy for colon cancer. Methods: 20-80 aged patients with stage III colon cancer who underwent curative surgery were randomly assigned to receive S-1 (80, 100, or 120 mg/day according to BSA on days 1 to 28, followed by 14 days rest, 4 courses) or UFT/LV (UFT: 300 to 600 mg/day according to BSA and, LV: 75 mg/day on days 1 to 28, followed by 7 days rest, 5 courses). Primary endpoint was DFS. Sample size was 1,480 determined with one-sided alpha of 0.05, power of 0.80, and non-inferiority margin of hazard ratio (HR) of 1.29. Results: Among 1535 enrolled patients between Apr. 2009 and Jun. 2010, 1518 patients (758 in S-1 group, 760 in UFT/LV group) were included in the efficacy analysis. Median follow-up was 41.3 months, the mean age at enrollment was 64.5 years, wide lymph node dissection (D3) was done in 79.8%, the median number of dissected lymph nodes was 17, and stage IIIA/IIIB/IIIC were 15%/71%/14%. The 3-year DFS rate was 75.5% in S-1 group and 72.5% in UFT/LV group. The HR of DFS was 0.85 (95%CI: 0.70-1.03) and non-inferiority of S-1 was demonstrated (p<0.0001). The completion rate of the protocol treatment was 76.5% in S-1 group and 72.5% in UFT/LV group. The overall incidence of grade ≥3 adverse events (AEs) in S-1 group and UFT/LV group were 16.0% and 14.4%: 4.4% and 5.5% for diarrhea, 4.9% and 3.5% for anorexia, 0.7% and 0.4% for leucopenia, 0.9% and 0.1% for anemia, 0.1% and 0.4% for thrombocytopenia, 1.2% and 1.5% for hyperbilirubinemia, 0.8% and 2.1% for AST elevation, and 1.1% and 3.3% for ALT elevation, respectively. Conclusions: Adjuvant therapy of S-1 for stage III colon cancer was demonstrated to be non-inferior in DFS to that of UFT/LV. Although AE profiles differed between S-1 group and UFT/LV group in this trial, incidence and degree of AEs were acceptable, and the completion rate of the protocol treatment was high. Adjuvant chemotherapy using S-1 will be a treatment option for stage III colon cancer. Clinical trial information: NCT00660894.

scholarly journals Updated 5-year survival and exploratory T x N subset analyses of ACTS-CC trial: a randomised controlled trial of S-1 versus tegafur-uracil/leucovorin as adjuvant chemotherapy for stage III colon cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (6) ◽  
pp. e000428 ◽  
Author(s):  
Tetsuya Kusumoto ◽  
Megumi Ishiguro ◽  
Eiji Nakatani ◽  
Motoki Yoshida ◽  
Tsukasa Inoue ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Controlled Trial ◽  
Disease Free Survival ◽  
Stage Iiib ◽  
Phase Iii ◽  
Stage Iii ◽  
Stage Iii Colon Cancer

ObjectiveAdjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC), a randomised phase III trial, demonstrated that adjuvant therapy with S-1 for stage III colon cancer was non-inferior in 3-year disease-free survival (DFS) to that of tegafur-uracil plus leucovorin (UFT/LV). We updated DFS and overall survival (OS) and performed T x N subset analysisMethodsA total of 1518 patients with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80–120  mg/day on days 1–28 every 42 days, four courses) or UFT/LV (UFT: 300–600  mg/day and LV: 75  mg/day on days 1–28 every 35 days, five courses)ResultsThe 5-year DFS rates of the S-1 and UFT/LV group were 70.2 % and 66.9 %, respectively (HR 0.88; 95%  CI 0.74 to 1.06; p=0.177), and non-inferiority of DFS was reconfirmed with a median of 63.5-month follow-up. The similarity of OS was also confirmed (HR 0.92; 95%  CI 0.72 to 1.17; p=0.488); 5-year OS rates of the S-1 and UFT/LV group were 86.0 % and 84.4 %, respectively. No significant interactions were identified between the major baseline characteristics and DFS of the S-1 and UFT/LV groups, except for histological type; S-1 was more favourable in patients with poorly differentiated adenocarcinoma. Patient outcomes were well separated by TNM-substages (IIIA/IIIB/IIIC). With the patients divided into 20 subsets by T and N factors, the DFS and OS rates of T3 and N1 subset, which accounted for 62 % of stage IIIB patients and 44 % of all studied subjects, were significantly better than those of the other subsets in stage IIIB and similar to those of stage IIIA.ConclusionsAdjuvant therapy of S-1 for stage III colon cancer was reconfirmed to be non-inferior in DFS to those of UFT/LV after long follow-up. No difference in OS was also demonstrated. T3N1 patients might be considered separately from other patients included in stage IIIB because of its favourable outcome.Trial registration numberNCT00660894.

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.

Effect of postoperative complications on adjuvant chemotherapy use in stage III colon cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3608-3608
Author(s):  
Ryan P Merkow ◽  
David J Bentrem ◽  
Mary Frances Mulcahy ◽  
Clifford Y. Ko ◽  
Karl Y. Bilimoria
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Postoperative Complications ◽  
Adjuvant Therapy ◽  
Anastomotic Leak ◽  
The United States ◽  
Stage Iii ◽  
Treatment Gap ◽  
Stage Iii Colon Cancer ◽  
National Quality

3608 Background: The National Quality Forum has endorsed the use of adjuvant chemotherapy in stage III colon cancer, yet a substantial treatment gap exists in the United States. Our objective was to evaluate the contribution of postoperative complications on the use of adjuvant therapy after colectomy for cancer. Methods: Patients from the National Surgical Quality Improvement Program and the National Cancer Data Base who underwent colon resection for cancer were linked (2006-2008). The association of complications on adjuvant chemotherapy use was assessed using multivariable regression models. Results: From 140 hospitals, 2368 patients underwent resection for stage III colon adenocarcinoma. Overall, 36.8% (871/2,368) patients were not treated with adjuvant therapy, of which 47.8% (416/871) had documented severe comorbidities or advanced age (≥80) as the reason for no adjuvant therapy receipt. Of the remaining 455 patients, 21.3% (97/455) had ≥1 serious complication that could account for adjuvant therapy omission. The remaining 41.1% (358/871) patients did not have a documented reason for not recieving adjuvant therapy. Complications associated with adjuvant therapy omission were abscess/anastomotic leak (OR 1.91, 95% CI 1.02-3.59), renal failure (OR 7.16, 95% CI 1.92-26.79), prolonged ventilation (OR 7.92, 95% CI 2.97-21.13), re-intubation (OR 5.69, 95% CI 2.13-15.18), and pneumonia (OR 4.05, 95% CI 2.07-7.90). Abscess/anastomotic leak was associated with a 28-day delay in time to adjuvant chemotherapy (73 vs. 45 days, p<0.05). Superficial surgical site infection did not decrease adjuvant therapy receipt but delayed the time to its use (57 vs. 44 days, p<0.05). The occurrence of postoperative sepsis was associated with a 15-day delay to adjuvant chemotherapy (60 vs. 45 days, p<0.05). Conclusions: Serious postoperative complications explained nearly one quarter of the adjuvant chemotherapy treatment gap among stage III colon cancer patients. Postoperative complications affect treatment utilization and should be considered when calculating adherence with the Stage III adjuvant therapy for colon cancer measure. Judging provider performance using quality metrics is challenging without clinical data.

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