Chronicle
Chemotherapy or no chemotherapy in clear margins after neoadjuvant chemoradiation in locally advanced rectal cancer: a randomised phase III trial of control versus capecitabine plus oxaliplatin [CHRONICLE]
Phase 3N = 113NCT00427713
- Population
- Patients with locally advanced rectal cancer after fluoropyrimidine-based chemoradiotherapy and curative resection
- Design
- Randomised phase 3 trial: after fluoropyrimidine-based chemoradiotherapy and curative resection, patients were randomised to observation or six cycles of XELOX (capecitabine plus oxaliplatin). The primary end point was disease-free survival; 390 patients were required in each arm to detect an improvement in 3-year disease-free survival from 40% to 50.5% (85% power, two-sided 5% significance). The study closed prematurely in 2008 because of poor accrual; 113 patients were randomised (observation n=59, XELOX n=54).
- Primary endpoint
- DFS
- Arms
- Observation (control, n = 59): No further chemotherapy after chemoradiotherapy and curative resection
- Adjuvant XELOX (experimental, n = 54): Six cycles of capecitabine plus oxaliplatin (XELOX) after chemoradiotherapy and curative resection
- People
- Glynne-Jones R
DFSHR 0.80 (95% CI 0.38–1.69)Δ 36-month DFS+7 pointsOSHR 1.18 (95% CI 0.43–3.26)Δ 36-month OS+1 points
Show the numbers
| Endpoint | Analysis | Adjuvant XELOX | Observation | Effect |
|---|---|---|---|---|
| DFSRandomised patients (113); analysis population not stated in the abstract3-year disease-free survival (primary end point) | primarymedian follow-up 44.8 monthsGlynne-Jones 2014 | 78% at 3 y | 71% at 3 y | HR 0.80 (95% CI 0.38–1.69)P=0.56After a median follow-up of 44.8 months, 16 patients (27%) in the observation arm and 12 (22%) in the XELOX arm had relapsed or died. Compliance was poor: 93% of those allocated chemotherapy started and 48% completed six cycles; protocolised dose reductions in XELOX were 39% and grade 3/4 toxicity 40%. The study closed early because of poor accrual and was underpowered. |
| OSRandomised patients (113); analysis population not stated in the abstract3-year overall survival (secondary end point) | primarymedian follow-up 44.8 monthsGlynne-Jones 2014 | 89% at 3 y | 88% at 3 y | HR 1.18 (95% CI 0.43–3.26)P=0.75 |
| Endpoint | Analysis | Adjuvant XELOX | Observation | Effect |
|---|---|---|---|---|
| DFSRandomised patients (113); analysis population not stated in the abstract3-year disease-free survival (primary end point) | primarymedian follow-up 44.8 monthsGlynne-Jones 2014 | 78% at 3 y | 71% at 3 y | HR 0.80 (95% CI 0.38–1.69)P=0.56After a median follow-up of 44.8 months, 16 patients (27%) in the observation arm and 12 (22%) in the XELOX arm had relapsed or died. Compliance was poor: 93% of those allocated chemotherapy started and 48% completed six cycles; protocolised dose reductions in XELOX were 39% and grade 3/4 toxicity 40%. The study closed early because of poor accrual and was underpowered. |
| OSRandomised patients (113); analysis population not stated in the abstract3-year overall survival (secondary end point) | primarymedian follow-up 44.8 monthsGlynne-Jones 2014 | 89% at 3 y | 88% at 3 y | HR 1.18 (95% CI 0.43–3.26)P=0.75 |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 0.8 | 0.38–1.69 |
| OS | 1.18 | 0.43–3.26 |
Appears in
Sources
Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows HM, et al. Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol. 2014;25(7):1356-1362.