Table 2.
Characteristics of the randomised trials comparing different chemoradiation regimens in anal cancer
| Trial name (years) | Number of patients | Design | RT dose | Testing 1 | Testing 2 | Planned gap | Primary endpoint |
|---|---|---|---|---|---|---|---|
|
RTOG 87-04/ECOG (1988–1991) |
291 | 5-FU/RT vs 5-FU/MMC/RT | Phase I 45–56 Gy median 48 Gy then biopsy of residual disease. 9 Gy boost if + | Addition of MMC 10 mg/m2 days 1 and 29 to 5-FU-based CRT | 4–6 weeks after 45–50.4 Gy if biopsy+ | Disease-free survival | |
|
RTOG 98-11 (1998–2005) |
644 | NACT Cisplat/5-FU then 5-FU/Cisplat/RT (i.e. 4 courses) vs. 5-FU/MMC/RT |
Phase I 45 Gy/25# in 5–6.5 weeks. T3/T4, N+ or residual T2 boost to 54–59 Gy |
NACT with 5-FU 1000 mg/m2 days 1–4, 29–32 and cisplatin 75 mg/m2 then CRT 5-FU/Cisplat versus MMC 10 mg/m2 days 1 and 29, and 5-FU 1000 mg/m2 days 1–4, 29–32 CRT | Max 10-day gap for skin intolerance but median OTT = 49 days | Disease-free survival | |
|
ACT II (UKCCCR) (2001–2008) |
940 | 2×2 factorial 5-FU/MMC versus 5-FU Cisplat CRT and consolidation 5-FU/Cisplat versus control |
Phase I 30/6 Gy/17# in 3.5 weeks then phase II 19.8 Gy/11# conformal. Total 50.4 Gy/28#/38 days, no gap |
Cisplatin 60 mg/m2 days 1 and 29 versus 12 mg/m2 MMC day 1 with 5-FU 1000 mg/m2 days 1–4, 29–32 CRT | Consolidate 2 courses 5-FU 1000 mg/m2 and cisplatin 60 mg/m2 |
No gap OTT 38 days |
Relapse-free survival |
|
ACCORD-03 (1999–2005) |
307 |
2×2 factorial NACT (5-FU/Cisplat- 2 cycles) versus no NACT. Standard versus high-dose boost for responders |
Phase I 45 Gy/25#/33 days, 3-week gap, then 15 Gy boost for standard arms. 20–25 Gy boost (high-dose arms) for responders. 40% received brachytherapy boost |
NACT with 5-FU 800 mg/m2 days 1–4, 29–32 and cisplatin 80 g/m2 on days 1 and 29, then CRT 5-FU/Cisplat on days as above with RT |
Dose escalation of RT boost. 15 Gy boost standard arms. 20–25 Gy boost (high-dose arms) for responders |
3 weeks after 45 Gy CRT completed |
Colostomy-free survival. Secondary end points included local control (LC), overall survival (OS), and cancer-specific survival |
RT radiotherapy, CRT chemoradiation, 5-FU 5-fluorouracil, Cisplatin cisplatinum, MMC mitomycin C, Gy Grays, NACT neoadjuvant chemotherapy, NS not significant, HDRT high-dose radiotherapy, OTT overall treatment time