RTOG 98-11
Fluorouracil, mitomycin, and radiotherapy versus fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal (US Gastrointestinal Intergroup RTOG 98-11)
Phase 3N = 682NCT00003596
- Population
- Patients with anal canal carcinoma. In the first report, median age 55 years, 69% women, 27% with tumour diameter greater than 5 cm and 26% with clinically positive nodes.
- Design
- US Gastrointestinal Intergroup multicentre phase 3 randomised trial, 682 patients enrolled between 31 October 1998 and 27 June 2005, stratified by sex, clinical nodal status and tumour diameter. Mitomycin-based group (341): fluorouracil 1000 mg/m2 on days 1-4 and 29-32 plus mitomycin 10 mg/m2 on days 1 and 29 with radiotherapy (45-59 Gy). Cisplatin-based group (341): fluorouracil 1000 mg/m2 on days 1-4, 29-32, 57-60 and 85-88 plus cisplatin 75 mg/m2 on days 1, 29, 57 and 85 with radiotherapy (45-59 Gy; start day 57). Primary endpoint 5-year disease-free survival; secondary endpoints overall survival and time to relapse.
- Primary endpoint
- DFS
- Arms
- Fluorouracil, mitomycin and radiotherapy (control, n = 341): Fluorouracil 1000 mg/m2 on days 1-4 and 29-32, mitomycin 10 mg/m2 on days 1 and 29, radiotherapy 45-59 Gy
- Fluorouracil, cisplatin and radiotherapy (experimental, n = 341): Fluorouracil 1000 mg/m2 on days 1-4, 29-32, 57-60 and 85-88, cisplatin 75 mg/m2 on days 1, 29, 57 and 85, radiotherapy 45-59 Gy starting on day 57
- People
- Ajani JA, senior author Willett C, US Gastrointestinal Intergroup (Radiation Therapy Oncology Group)
Δ 60-month DFS−6 pointsΔ 60-month OS−5 pointsΔ 60-month Locoregional failure+8 pointsΔ Colostomy rate+9 pointsΔ 60-month DFS−10 pointsΔ 60-month OS−7.6 points
Show the numbers
| Endpoint | Analysis | Fluorouracil, cisplatin and radiotherapy | Fluorouracil, mitomycin and radiotherapy | Effect |
|---|---|---|---|---|
| DFS644 assessable patients of 682 enrolled | primarymedian follow-up 2.51 yearsAjani 2008 | 54% at 5 y (46–60%) | 60% at 5 y (53–67%) | P=.175-year disease-free survival, the primary endpoint, in the initial report (644 assessable patients; median follow-up 2.51 years for all patients). |
| OS644 assessable patients of 682 enrolled | primarymedian follow-up 2.51 yearsAjani 2008 | 70% at 5 y (63–76%) | 75% at 5 y (67–81%) | P=.105-year overall survival, a secondary endpoint, in the initial report. |
| Locoregional failure644 assessable patients of 682 enrolledLocal-regional recurrence rate at 5 years, as reported. | primarymedian follow-up 2.51 yearsAjani 2008 | 33% at 5 y (27–40%) | 25% at 5 y (20–30%) | 5-year local-regional recurrence; the abstract gives no p-value for it. Distant metastasis at 5 years: 15% (95% CI 10%-20%) with mitomycin-based and 19% (14%-24%) with cisplatin-based treatment. |
| Colostomy rate644 assessable patients of 682 enrolledCumulative rate of colostomy; the abstract gives no time point. | primarymedian follow-up 2.51 yearsAjani 2008 | 19% | 10% | P=.02The cumulative colostomy rate was significantly better with mitomycin-based than cisplatin-based treatment. Severe haematologic toxicity was worse with mitomycin-based treatment (P < .001). |
| DFS649 analysable patients of 682 accrued | long term-updateGunderson 2012 | 57.8% at 5 y | 67.8% at 5 y | P=.0065-year disease-free survival (649 analysable patients), estimated by the Kaplan-Meier method and compared by log-rank test, in the long-term update. The abstract does not give the median follow-up of the update or confidence intervals. Colostomy-free survival (P = .05), locoregional failure (P = .087) and colostomy failure (P = .074) showed a trend toward statistical significance. |
| OS649 analysable patients of 682 accrued | long term-updateGunderson 2012 | 70.7% at 5 y | 78.3% at 5 y | P=.0265-year overall survival in the long-term update. The abstract's conclusion is that radiotherapy with fluorouracil and mitomycin has a statistically significant, clinically meaningful impact on disease-free and overall survival versus induction plus concurrent fluorouracil and cisplatin. |
| Endpoint | Analysis | Fluorouracil, cisplatin and radiotherapy | Fluorouracil, mitomycin and radiotherapy | Effect |
|---|---|---|---|---|
| DFS644 assessable patients of 682 enrolled | primarymedian follow-up 2.51 yearsAjani 2008 | 54% at 5 y (46–60%) | 60% at 5 y (53–67%) | P=.175-year disease-free survival, the primary endpoint, in the initial report (644 assessable patients; median follow-up 2.51 years for all patients). |
| OS644 assessable patients of 682 enrolled | primarymedian follow-up 2.51 yearsAjani 2008 | 70% at 5 y (63–76%) | 75% at 5 y (67–81%) | P=.105-year overall survival, a secondary endpoint, in the initial report. |
| Locoregional failure644 assessable patients of 682 enrolledLocal-regional recurrence rate at 5 years, as reported. | primarymedian follow-up 2.51 yearsAjani 2008 | 33% at 5 y (27–40%) | 25% at 5 y (20–30%) | 5-year local-regional recurrence; the abstract gives no p-value for it. Distant metastasis at 5 years: 15% (95% CI 10%-20%) with mitomycin-based and 19% (14%-24%) with cisplatin-based treatment. |
| Colostomy rate644 assessable patients of 682 enrolledCumulative rate of colostomy; the abstract gives no time point. | primarymedian follow-up 2.51 yearsAjani 2008 | 19% | 10% | P=.02The cumulative colostomy rate was significantly better with mitomycin-based than cisplatin-based treatment. Severe haematologic toxicity was worse with mitomycin-based treatment (P < .001). |
| DFS649 analysable patients of 682 accrued | long term-updateGunderson 2012 | 57.8% at 5 y | 67.8% at 5 y | P=.0065-year disease-free survival (649 analysable patients), estimated by the Kaplan-Meier method and compared by log-rank test, in the long-term update. The abstract does not give the median follow-up of the update or confidence intervals. Colostomy-free survival (P = .05), locoregional failure (P = .087) and colostomy failure (P = .074) showed a trend toward statistical significance. |
| OS649 analysable patients of 682 accrued | long term-updateGunderson 2012 | 70.7% at 5 y | 78.3% at 5 y | P=.0265-year overall survival in the long-term update. The abstract's conclusion is that radiotherapy with fluorouracil and mitomycin has a statistically significant, clinically meaningful impact on disease-free and overall survival versus induction plus concurrent fluorouracil and cisplatin. |
Appears in
Sources
Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008;299(16):1914-21.
Gunderson LL, Winter KA, Ajani JA, Pedersen JE, Moughan J, Benson AB 3rd, et al. Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol. 2012;30(35):4344-51.