Comparison of adverse events during 5-fluorouracil versus 5-fluorouracil/oxaliplatin adjuvant chemotherapy for 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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Adjuvant Chemotherapy Use and Adverse Events Among Older Patients With Stage III Colon Cancer

JAMA ◽

10.1001/jama.2010.272 ◽

2010 ◽

Vol 303 (11) ◽

pp. 1037 ◽

Cited By ~ 105

Author(s):

Katherine L. Kahn

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Adverse Events ◽

Older Patients ◽

Stage Iii ◽

Stage Iii Colon Cancer

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Faculty Opinions recommendation of Adjuvant chemotherapy use and adverse events among older patients with stage III colon cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2627959.2974054 ◽

2010 ◽

Author(s):

Richard Goldberg ◽

Hanna Sanoff

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Adverse Events ◽

Older Patients ◽

Stage Iii ◽

Stage Iii Colon Cancer

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Preplanned initial safety analysis of ACTS-CC 02 trial: A large randomized phase III trial of SOX versus UFT/LV as adjuvant chemotherapy for high-risk stage III colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.572 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 572-572 ◽

Cited By ~ 4

Author(s):

Hiroya Takiuchi ◽

Naohiro Tomita ◽

Narikazu Boku ◽

Toshiaki Watanabe ◽

Kenjiro Kotake ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Adverse Events ◽

Curative Resection ◽

Phase Iii ◽

Stage Iii ◽

Postoperative Adjuvant Chemotherapy ◽

Stage Iii Colon Cancer ◽

To Receive

572 Background: The ACTS-CC 02 trial is designed to verify the superiority of postoperative adjuvant chemotherapy of S-1/Oxaliplatin (SOX) for patients with anyT, N2 colon cancer compared with UFT/Leucovorin (UFT/LV), which is one of standard adjuvant chemotherapies in Japan. To date, there have been no reported phase III trials evaluating SOX as postoperative adjuvant chemotherapy. This report presents initial safety data obtained from 50 patients who received SOX in the trial. Methods: Patients who underwent curative resection for anyT, N2 colon cancer were randomly assigned to receive either SOX (100 mg/m2 of oxaliplatin on day1, and 80 to 120 mg/day according to body surface area (BSA) of S-1 on days 1-14, every 21 days, 8 courses) or UFT/LV (300 to 600 mg/day according to BSA of UFT and 75 mg/day of LV on days 1-28, every 35 days, 5 courses). Data were collected from initial consecutive 50 patients assigned to the SOX group and analyzed when they were considered evaluable for safety as planned in the protocol. This ongoing trial is designed to accrue 1200 patients. As of September 15, 2011, 319 patients have been accrued. Results: Of 50 patients assigned to receive SOX, 48 were evaluable for safety. The median number of treatment courses was 5 (range: 1-8). The relative dose intensity of S-1 was 83.8% and that of oxaliplatin was 86.6%. Grade 3 adverse events were neutropenia (14.6%), thrombocytopenia (2.1%), ALT elevation (2.1%), diarrhea (8.3%), fatigue (2.1%), and peripheral sensory neuropathy (2.1%). Grade 4 adverse effects were not observed. Conclusions: In this initial safety analysis, the incidence and severity of adverse events with SOX were acceptable in patients with high risk stage III colon cancer after curative resection. Enrollment of patients is ongoing.

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Baseline creatinine clearance as an indicator of severe adverse events associated with oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer: Safety analysis of the phase III Japanese ACHIEVE trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.667 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 667-667

Author(s):

Masato Nakamura ◽

Masahito Kotaka ◽

Tetsuya Eto ◽

Dai Manaka ◽

Junichi Hasegawa ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Adverse Events ◽

Creatinine Clearance ◽

Disease Free Survival ◽

Phase Iii ◽

Stage Iii ◽

Stage Iii Colon Cancer ◽

Baseline Creatinine ◽

Grade 3

667 Background: The phase III ACHIEVE trial (JFMC47), a project of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA), was established to prospectively analyze data from several randomized trials to test whether 3-month (arm 3) oxaliplatin-based adjuvant (FOLFOX4, mFOLFOX6, or XELOX) treatment is non-inferior to 6-month (arm 6) treatment in terms of disease-free survival in patients (pts) with stage III colon cancer. It aims to reveal the association between baseline characteristics and ≥ grade 3 adverse events (AEs) related to XELOX and mFOLFOX6, particularly focusing on the role of baseline creatinine clearance (CCr) on ≥ grade 3 AEs. Methods: This association was assessed using the Cox proportional hazards model. Results: During 2012–2014, 1,313 pts were randomized from 244 centers; 1,301 were included in the intention-to-treat population. Among the safety population (N = 1,277; 642, arm 3; 635, arm 6), the overall incidence of ≥ grade 3 AEs was 29% in arm 3 and 43% in arm 6 (p < 0.0001). Neuropathy of ≥ grade 2 was more frequent in arm 6 than in arm 3 (37% vs. 14%; p < 0.0001). Regarding the fluoropyrimidine backbone, grade 3–4 neutropenia was more with mFOLFOX6 than XELOX (30% vs. 12%), whereas grade 3–4 anorexia (2% vs. 5%) and grade 3–4 diarrhea (1% vs. 6%) were more with XELOX. Multivariate analysis, including treatment duration, regimen, CCr ( < 50 vs. > 50 mL/min), age, and sex, showed that CCr had a statistically significant impact on the occurrence of ≥ grade 3 AEs (hazard ratio = 0.44, p < 0.0001). Pts with CCr < 50 may have had more frequent ≥ grade 3 AEs independent of other factors, such as age. Conclusions: Grade 3 or higher AEs related to XELOX or mFOLFOX6 may be associated with the degree of CCr. Clinical trial information: UMIN 000008543.

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