Efficacy of 6 Months of Capecitabine vs. 12 Months as Adjuvant Chemotherapy for Patients with Stage III CRC

14 Oct, 20

Background

Surgery is the main treatment for colorectal cancer (CRC), while postoperative adjuvant chemotherapy is used to reduce recurrence and improve prognosis. The optimal treatment period for oral 5-FU drugs as the adjuvant postoperative chemotherapy for CRC remains inconclusive.

Aim

To compare 6 months vs. 12 months of capecitabine as adjuvant chemotherapy for patients with stage III CRC

Patient profile

Patients with
- Histologically confirmed stage III colon adenocarcinoma
- curatively resected with extended lymph node dissection (D2 or D3 in the Japanese Classification of Colorectal Carcinoma, 7th edition);15
- aged 20–79 years
- Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0–1
- no prior chemotherapy or radiotherapy for CRC
- no other active malignancies
- adequate oral intake
- preserved major organ functions
- no uncontrollable severe infection

Methods

Multi-institutional, open-label, randomised, phase III study

Study Endpoints

The primary endpoint was disease-free survival (DFS)
Secondary endpoints were relapse-free survival (RFS), overall survival (OS), and adverse events

Results

Efficacy

12 months capecitabine did not show superiority to 6 months regimen in terms of DFS
However, 12 months capecitabine showed significant superiority to 6 months both in RFS and OS

Figure 1. Efficacy analysis: Disease-free survival and relapse-free survival and overall survival

The difference in the hazard rate between the two groups from year 0.5 to 1.5 was statistically significant (HR = 0.713; p = 0.0149)
The subgroup analysis showed a reduced risk of recurrence in the 12M group compared to the 6M group, particularly in the male sex, open surgical approach, and the T4 subgroup

Safety

The incidence of overall grade 3–4 adverse events was almost comparable in both groups
Incidence rates of adverse events in 6M was 91.7% and 94.7% in 12 M groups.
- Hand-foot syndrome (HFS) was the most commonly reported AE
- In 12 M group, the incidence of HFS was higher than in 6M group

Conclusions

The study demonstrated that 12-month adjuvant capecitabine did not demonstrate superior DFS to that of 6-month however, OS and RFS was statistically higher in the 12M group
The study researchers suggested 12 months of capecitabine monotherapy, along with 3 months of CAPOX with limited neurotoxicity, could be proposed as a treatment option without neurotoxicity

Reference

British Journal of Cancer.2019;120:689–696