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Long-term Update of U.S. GI Intergroup RTOG 98-11 Phase III Trial for Anal Carcinoma: Concurrent Chemoradiation with 5FU-Mitomycin Yields Better Disease-Free and Overall Survival than 5FU-Cisplatin

Reporter: Surbhi Grover, MD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 3 de octubre del 2011

Presenting Author: Leonard Gunderson

Background

• Randomized studies has shown definitive chemotherapy and radiation render a high local control and colostomy free survival (CFS) for patients with anal cancer (EORTC, Bartelink JCO 1997). Chemotherapy that is usually used is 5FU and mitomycin as per the historic Nigro study. Although, mitomycin has significant hematological, GI and pulmonary toxicities, elimination of mitomycin leads to worse local control and CFS (RTOG 87-04).
• Current study, RTOG 98-11 was designed to study the following: If mitomycin cannot be eliminated, could it be replaced with cisplatin, an agent known to have an effect on squamous histology.
• RTOG 98-11 was initially published in 2008 showed no difference in overall survival and disease free survival (OS or DFS) in the two arms. However, CFS was significantly improved in the mitomycin arm.
  
• Current abstract presents the updated long term data for RTOG 98-11 in regards to OS, DFS, colostomy failure (CF), CFS, distant metastasis (DM) and local-regional failure (LRF).

Methods

Six hundred eighty two patients with T2-T4 and any N status, squamous cell carcinoma of anus were randomized to:

1. 5FU (1000mg/m2 days 1-4, 29-32) +Mitomycin (10mg/m2 days 1 and 29) with concurrent radiation (45-59 Gy).
2. 5FU (1000mg/m2 days 1-4, 29-32, 57-60 and 85-88) + cisplatin (75mg/m2 on days 1, 29, 57, 85) with RT (45-59 Gy starting at day 57)

Patients were stratified by gender, size of the tumor, and nodal status.

Results

• Five year OS and DFS were improved in the mitomycin arm vs cisplatin arm (78.3% vs 70.7% p=0.02 and 67.8% vs 57.8% p=0.006).
• There was as trend towards benefit in the mitomycin arm in regards to CFS (72% vs 65% p=0.05), LRF (20% vs 26.4% p=0.087) and CF (12% vs 17.3% p=0.07), but these outcomes didn't reach statistical significance.
• On multivariate analysis, mitomycin treatment arm, female gender, smaller (2-5cm) tumor diameter, negative nodal status were significant predictors of OS and DFS.

Authors Conclusions

Given the significant OS benefit of 5FU+mitomycin with concurrent RT over cisplatin based chemoRT, 5FU+mitomycin with RT remains the standard of treatment for anal cancer.

Clinical and Scientific Implications:

In this study, 5FU/cisplatin chemotherapy was given neoadjuvantly for two months before concurrent chemoRT was started. It is possible that the there is no benefit in 5FU/cisplatin because of the delay in the concurrent chemoRT. May be we need a fair comparison of treatment schemes to actually rule out cisplatin completely?

We should continue to look at other strategies to improves outcomes, namely, IMRT to allow for dose escalation, early salvage therapy and novel biologic agents.

Mitomycin + 5FU concurrent with radiation remains the standard of care for treatment of anal cancer.