Phase III randomised trial comparing 6 vs. 12-month of capecitabine as adjuvant chemotherapy for patients with stage III colon cancer: final results of the JFMC37-0801 study

Abstract

Background Up to 6-months oxaliplatin-containing regimen is now widely accepted as a standard adjuvant chemotherapy for stage III colorectal cancer (CRC). However, oral fluoropyrimidine monotherapy is used for some part of patients, especially in Asian countries including Japan, and its optimal duration is yet to be fully investigated. Methods A total of 1306 patients with curatively-resected stage III CRC were randomly assigned to receive capecitabine (2500 mg/m 2 /day) for 14 out of 21 days for 6 ( n = 654) or 12 ( n = 650) months. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were relapse-free survival (RFS), overall survival (OS), and adverse events. Results The 3- and 5-year DFS were 70.0% and 65.3% in the 6M group and 75.3% and 68.7% in the 12M group, respectively ( p = 0.0549, HR = 0.858, 90% CI: 0.732–1.004). The 5-year RFS was 69.3% and 74.1% in the 6M and 12M groups, respectively ( p = 0.0143, HR = 0.796, 90% CI: 0.670–0.945). The 5-year OS was 83.2% and 87.6%, respectively ( p = 0.0124, HR = 0.727, 90% CI: 0.575–0.919). The incidence of overall grade 3–4 adverse events was almost comparable in both groups. Conclusions Although 12-month adjuvant capecitabine did not demonstrate superior DFS to that of 6-month, the observed better RFS and OS in the 12-month treatment period could be of value in selected cases.

S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial

“… 1 , 2 , 3 In Japan, oral fluoropyrimidines, such as capecitabine, tegafur-uracil and LV (UFT/LV), and S-1, are preferred because they have demonstrated favorable outcomes in patients with stage III colon cancer in Japanese randomized trials, and their treatment is convenient and associated with only mild toxicity. 4 , 5 , 6 , 7 However, stage III includes patient subgroups showing very poor outcomes, such as the N2 disease. 4 , 7 According to the Japanese Classification of Colorectal Carcinoma (7th edition), the main lymph nodes are defined as lymph nodes around the origin of the feeding arteries (i.e.…”

“… 4 , 5 , 6 , 7 However, stage III includes patient subgroups showing very poor outcomes, such as the N2 disease. 4 , 7 According to the Japanese Classification of Colorectal Carcinoma (7th edition), the main lymph nodes are defined as lymph nodes around the origin of the feeding arteries (i.e. the ileocolic, right colic, middle colic, or inferior mesenteric artery; Supplementary Figure S1 , available at https://doi.org/10.1016/j.esmoop.2021.100077 ).…”

S-1 and Oxaliplatin Versus Tegafur-uracil and Leucovorin as Postoperative Adjuvant Chemotherapy in Patients With High-risk Stage III Colon Cancer (ACTS-CC 02): A Randomized, Open-label, Multicenter, Phase III Superiority Trial

“…[1][2][3] In Japan, oral fluoropyrimidines such as capecitabine, tegafur-uracil and leucovorin (UFT/LV), and S-1 have been preferred because oral fluoropyrimidines alone demonstrated favorable outcomes in patients with stage III colon cancer, most of whom underwent D3 lymph node dissection (3-year disease-free survival [DFS] rate, 70.0%-82.0%), in Japanese randomized trials, and their treatment is convenient and associated with mild toxicities. [4][5][6][7] However, stage III disease includes subgroups of patients with very poor outcomes. In the ACTS-CC trial, the 3-year DFS rate in patients with stage IIIA, IIIB, and IIIC disease who received UFT/LV were 87.9%, 74.2%, and 46.4%, respectively.…”

“…4 In the JFMC37-0801 study, the 3-year DFS rate in patients who received capecitabine showed a similar trend. 7 There remains room for improvement in the outcomes of patients with such high-risk stage III disease. More aggressive regimens including oxaliplatin are expected to be effective.…”

Dealing with pre-existing chronic neutropenia in cancer patients— considerations and consequences in the clinical praxis

“…Capecitabine (an oral prodrug of 5-fluorouracil) and 5-fluorouracil have long been the backbone of chemotherapy for stages II–III colon cancer in the adjuvant setting [ 13 ]. The duration of treatment has been proven most efficient when given for six months [ 14 ]. Haematological treatment requirements are neutrophils ≥1.5 × 10 9 /L and thrombocytes ≥100 × 10 9 /L.…”