Mature Survival Results with Preoperative Cisplatin, Protracted Infusion 5-FU, and 45 GY Radiotherapy for Esophageal Cancer
Diana Stripp, MD
University of Pennsylvania Cancer Center
Last Modified: November 5, 2001
Presenter: L. Kleinberg
Presenter's Affiliation: Johns Hopkins Oncology Center, Baltimore, MD
Type of Session: Scientific
- Neoadjuvant chemoradiation for Esophageal cancer is controversial, however, many patients are offered this therapy as a standard of treatment.
- Randomized trials has shown mixed results
- The US Intergroup study closed early due to lack of recruitment
- This study is designed to assess long-term survival results after cisplatin, protracted infusion 5-FU and concurrent radiotherapy followed by surgical resection of esophageal cancer.
- 92 patients with esophageal cancer were treated on two sequential protocols of preoperative chemoradiotherapy.
Surgery generally occurred 4-6 weeks after completion of the planned preoperative
therapy. Transhiatal resection was performed whenever possible.
- Trial A (1989- 1994), 50 patients were treated with 44 Gy RT (2 Gy/day) along with concurrent 5FU protracted infusion and cisplatin.
- Trial B (1995-1997, 42 patients), the chemotherapy doses of 5FU and cisplatin were reduced during RT and three cycles paclitaxel and cisplatin were given postoperatively.
Results65 pts with adenocarcinoma and 27 with squamous cell carcinoma of the esophagus were enrolled.
93% (86/92) underwent surgery; 87% (80/92) were completely resected with negative margins; 33% (30/92) had pathologic complete response.
Median follow-up of surviving patients is 63.5 (34-121) months. The median survival and disease specific survival of all enrolled patients is 35 months and 59 months.
Five year survival and disease specific survival is 40% and 49% respectively.
Patients with a pathologic complete response had 67% survival at 5 years (median not reached) whereas the remainder of the patients had 5 year survival of 26% (median 21 months) (p<.001).
For the 21 patients alive after 5 years, there were two disease related deaths and all others were disease free.
Eight pts with pathologic stage I tumor at the time of surgery had survival similar to those with a complete response to preoperative therapy.
Median survival for patients with pathologic stage IIA and above were less than 22 months.
Based on 50 recurrences, the pattern of initial failure was local/regional alone 6% (5/90), local/regional plus distant 3% (3/90), and distant alone 47% (42/90). The results were similar for trial A and trial B.
There were no differences in survival or response rate between those with adenocarcinoma and squamous cell carcinoma.
- The promising 5 year survival results and low rate of late cancer related deaths suggests that these regimens of intensive neoadjuvant therapy may improve the overall cure rate.
- Pathologic stage after neoadjuvant therapy is an important predictor of survival and may be useful in selecting patients for intensified adjuvant therapies.
- Although complete response of local disease is associated with long-term survival, isolated local failure is uncommon indicating that efforts to improve the therapeutic outcome should focus on optimizing systemic therapy rather than intensifying the radiotherapy.
- Additional randomized data are needed to fully assess the benefits of this therapeutic approach.
Clinical/Scientific ImplicationsProspective randomized trials are needed to confirm the findings of this study.
Because of the generally poor outcome with standard therapies in the treatment of pancreatic cancer, patients should continue to be enrolled in clinical trials to identify promising therapies.
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