Rektum-III trial, cape vs 5FU

Background

Randomized, open-label, multicentre, non-inferiority phase III trial (n=392) in stage II–III locally advanced rectal cancer, comparing capecitabine vs fluorouracil within neoadjuvant or adjuvant chemoradiotherapy regimens.

Interventions and follow up

Arm A (capecitabine): 2 cycles capecitabine (2500 mg/m2 D1–14, repeated D22), then chemoradiotherapy (50.4 Gy + capecitabine 1650 mg/m2 D1–38), then 3 cycles capecitabine
Arm B (fluorouracil): 2 cycles bolus fluorouracil (500 mg/m2 D1–5, repeated D29), then chemoradiotherapy (50.4 Gy + infusional fluorouracil 225 mg/m2 daily), then 2 cycles bolus fluorouracil
Primary endpoint: overall survival (non-inferiority)
Median follow up: 52 months

Results

5-yr OS: 76% vs 67%, arm A vs B; P=.0004 for non-inferiority; post-hoc superiority P=.05
3-yr DFS: 75% vs 67%; P=.07
Local recurrence (3-yr): similar between arms

Adverse events

Gastrointestinal: diarrhea most common, any grade 53% vs 44% (arm A vs B); proctitis 16% vs 5%
Dermatologic/constitutional: hand-foot skin reaction 31% vs 2%; fatigue 28% vs 15%

Conclusions

Capecitabine is non-inferior (and possibly superior) to fluorouracil in neoadjuvant or adjuvant chemoradiotherapy for locally advanced rectal cancer, supporting oral capecitabine as a convenient alternative to infusional 5-FU.

Key Limitations

Modest sample size; the trial pooled patients receiving radiotherapy in neoadjuvant and adjuvant settings. Superiority was a post-hoc finding only and marginal (P=.05). Open-label design.

Clinical Context

Supports substitution of capecitabine for infusional 5-FU as a radiosensitizer in rectal cancer chemoradiotherapy, now widely adopted in ASCO/ESMO-aligned practice for both LARC and adjuvant settings.

References