Polish II
Short-course preoperative radiotherapy with consolidating chemotherapy versus preoperative chemoradiation in patients with unresectable rectal cancer: phase III study
Phase 3N = 541NCT00833131
- Population
- Patients with fixed cT3 or cT4 rectal cancer
- Design
- Randomised phase 3 trial in patients with fixed cT3 or cT4 rectal cancer. Group A: 5 x 5 Gy followed by three cycles of FOLFOX4. Group B: 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus fluorouracil 325 mg/m2 per day and leucovorin 20 mg/m2 per day during the first and fifth week of irradiation, with five weekly infusions of oxaliplatin 50 mg/m2. The protocol was amended in 2012 to allow oxaliplatin to be omitted in both groups. 541 patients entered; 515 were eligible for analysis (261 in group A and 254 in group B); median follow-up was 35 months.
- Primary endpoint
- R0 resection
- Arms
- 5 x 5 Gy then consolidation FOLFOX4 (group A) (experimental, n = 261): 5 x 5 Gy followed by three cycles of FOLFOX4
- Long-course chemoradiation with oxaliplatin (group B) (control, n = 254): 50.4 Gy in 28 fractions with two 5-day cycles of bolus fluorouracil 325 mg/m2 per day and leucovorin 20 mg/m2 per day in weeks 1 and 5, plus five weekly infusions of oxaliplatin 50 mg/m2
- People
- Bujko K
Δ R0 resection+6 pointsΔ pCR+4 pointsΔ 36-month OS+8 pointsΔ 36-month DFS+1 pointsΔ 36-month Locoregional failure+1 pointsΔ 36-month Cumulative incidence of distant metastases+3 points
Show the numbers
| Endpoint | Analysis | 5 x 5 Gy then consolidation FOLFOX4 (group A) | Long-course chemoradiation with oxaliplatin (group B) | Effect |
|---|---|---|---|---|
| R0 resectionEligible patients (515: 261 in group A, 254 in group B)R0 resection rate (primary end point) | primaryBujko 2016 | 77% | 71% | P=0.07 |
| pCREligible patients (515: 261 in group A, 254 in group B) | primaryBujko 2016 | 16% | 12% | P=0.17 |
| OSEligible patients (515: 261 in group A, 254 in group B)3-year overall survival (secondary end point) | primarymedian follow-up 35 monthsBujko 2016 | 73% at 3 y | 65% at 3 y | P=0.046 |
| DFSEligible patients (515: 261 in group A, 254 in group B) | primarymedian follow-up 35 monthsBujko 2016 | 53% at 3 y | 52% at 3 y | P=0.85 |
| Locoregional failureEligible patients (515: 261 in group A, 254 in group B)3-year cumulative incidence of local failure, as named in the abstract | primarymedian follow-up 35 monthsBujko 2016 | 22% at 3 y | 21% at 3 y | P=0.82 |
| Cumulative incidence of distant metastasesEligible patients (515: 261 in group A, 254 in group B) | primarymedian follow-up 35 monthsBujko 2016 | 30% at 3 y | 27% at 3 y | P=0.26 |
| Grade 3-4 acute toxicityEligible patients (515: 261 in group A, 254 in group B)Grade III-IV acute toxicity of preoperative treatment | primaryBujko 2016 | 23% | 21% | Any acute toxicity was 75% in group A and 83% in group B (acute toxicity was lower in group A, P=0.006); toxic deaths were 1% and 3%. |
| Surgical complicationsEligible patients (515: 261 in group A, 254 in group B)Postoperative complications | primaryBujko 2016 | 29% | 25% | P=0.18Late complications were 20% in group A and 22% in group B (P=0.54). |
| Endpoint | Analysis | 5 x 5 Gy then consolidation FOLFOX4 (group A) | Long-course chemoradiation with oxaliplatin (group B) | Effect |
|---|---|---|---|---|
| R0 resectionEligible patients (515: 261 in group A, 254 in group B)R0 resection rate (primary end point) | primaryBujko 2016 | 77% | 71% | P=0.07 |
| pCREligible patients (515: 261 in group A, 254 in group B) | primaryBujko 2016 | 16% | 12% | P=0.17 |
| OSEligible patients (515: 261 in group A, 254 in group B)3-year overall survival (secondary end point) | primarymedian follow-up 35 monthsBujko 2016 | 73% at 3 y | 65% at 3 y | P=0.046 |
| DFSEligible patients (515: 261 in group A, 254 in group B) | primarymedian follow-up 35 monthsBujko 2016 | 53% at 3 y | 52% at 3 y | P=0.85 |
| Locoregional failureEligible patients (515: 261 in group A, 254 in group B)3-year cumulative incidence of local failure, as named in the abstract | primarymedian follow-up 35 monthsBujko 2016 | 22% at 3 y | 21% at 3 y | P=0.82 |
| Cumulative incidence of distant metastasesEligible patients (515: 261 in group A, 254 in group B) | primarymedian follow-up 35 monthsBujko 2016 | 30% at 3 y | 27% at 3 y | P=0.26 |
| Grade 3-4 acute toxicityEligible patients (515: 261 in group A, 254 in group B)Grade III-IV acute toxicity of preoperative treatment | primaryBujko 2016 | 23% | 21% | Any acute toxicity was 75% in group A and 83% in group B (acute toxicity was lower in group A, P=0.006); toxic deaths were 1% and 3%. |
| Surgical complicationsEligible patients (515: 261 in group A, 254 in group B)Postoperative complications | primaryBujko 2016 | 29% | 25% | P=0.18Late complications were 20% in group A and 22% in group B (P=0.54). |