NSABP R-01, first adj chemo in LARC

Background

Phase III RCT in 555 patients with Dukes B or C rectal cancer treated by curative resection, randomized to surgery alone, postoperative chemotherapy, or postoperative radiotherapy. A landmark early adjuvant trial in rectal cancer.

Interventions and follow up

Arm A: Surgery alone (control)
Arm B: Postoperative adjuvant chemotherapy with 5-fluorouracil, semustine, and vincristine (MOF) x 8 cycles Q10W
Arm C: Postoperative radiation therapy
Primary endpoint: DFS and OS
Median follow up: mean 64.1 mo

Results

5-yr DFS: 30% vs 42% (Arm A vs B); cumulative odds of DFS favoring chemotherapy 1.50, 95% CI 1.13-1.99, P=.006
5-yr OS: 43% vs 53% (Arm A vs B); cumulative odds of OS favoring chemotherapy 1.30, 95% CI 0.95-1.79, P=.05
Local-regional recurrence (radiotherapy vs control): 16% vs 25%, P=.06; no significant DFS or OS change

Adverse events

Hematologic: Myelosuppression typical of 5-FU and semustine (chemotherapy arm)
GI/infectious: Gastrointestinal toxicity and infections; treatment generally tolerated with no unexpected toxicities

Conclusions

This historical trial demonstrated a disease-free and overall survival benefit of postoperative chemotherapy in resectable rectal cancer, with greater benefit observed in male patients. Adjuvant radiotherapy reduced local recurrence without a survival effect.

Key Limitations

Used the now-obsolete MOF regimen (semustine, vincristine) rather than modern fluoropyrimidine-based therapy. Predates total mesorectal excision and neoadjuvant chemoradiation, the contemporary standards. Sex-related benefit was an unplanned subgroup observation.

Clinical Context

NSABP R-01 was foundational in establishing adjuvant therapy for rectal cancer. Practice has since evolved to neoadjuvant chemoradiation or total neoadjuvant therapy with TME, as endorsed by ESMO. The specific MOF regimen is no longer used.

References