Safety data from the phase III Japanese ACHIEVE trial: part of an international, prospective, planned pooled analysis of six phase III trials comparing 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer

Abstract

BackgroundThe International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3).Patients and methodsACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator.ResultsBetween August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048).ConclusionsWe confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs.Trial registration number UMIN000008543, Results.

Forkhead box O3 promotes colon cancer proliferation and drug resistance by activating MDR1 expression

“…Colon cancer (CC), also known as colorectal or bowel cancer, is the third most frequent malignant cancer, and more than 65 percent of CC cases are found in developed countries (Kotaka et al, ). Aging is the most critical risk factor for CC, and other risk factors for CC include obesity, smoking, drinking, lack of physical activity, inflammatory bowel diseases, and inherited genetic disorders (Board, ; Theodoratou, Timofeeva, Li, Meng, & Ioannidis, ).…”

Shortening adjuvant chemotherapy in stage III colon cancer: are we ready for a change?

“…These results on toxicity were reproduced in the Adjuvant Chemotherapy for colon cancer with HIgh EVidencE trial (ACHIEVE) trial by Kotaka et al 7 in this issue of ESMO Open . These authors confirmed that delivering adjuvant therapy for only 3 months reduced the incidence of key adverse events.…”

Phase II study of capecitabine plus oxaliplatin (CapOX) as adjuvant chemotherapy for locally advanced rectal cancer (CORONA II)

“…Thus, a shorter duration of adjuvant CapOX therapy would be beneficial so long as efficacy is not affected. In this regard, the ACHIEVE trial confirmed that a shorter duration of oxaliplatin-based adjuvant chemotherapy resulted in a significant reduction of PSN in a Japanese population with Stage III colon cancer [30].…”