The key evidence supporting the use of this protocol comes from the landmark RTOG 8501 PHIII trialr which randomised 121 patients to receive radiotherapy alone (64Gy) vs chemoradiotherapy (4 cycles of cisplatin and fluorouracil commencing on day 1 of radiotherapy (RT) 50Gy in 25#). The trial was closed prematurely with 121 patients, when an interim analysis showed a significant survival advantage for chemoradiotherapy (five-year survival 27 versus 0 percent). Analysis of failure patterns showed a significant reduction in both locoregional and distant failure for chemoradiotherapy.
Almost half of the patients receiving chemoradiotherapy in the RTOG 8501r study developed locoregional relapse. This led to the exploration of dose escalation as a treatment strategy. Two phase I/II studies employing brachytherapy (RTOG 9207r and external beam boosts (INT0122)r failed to show results superior to those in the chemoradiotherapy arm of RTOG-8501.r
This study was followed up by the Intergroup Study - INT 0123r- 236 patients with non-metastatic oesophageal SCC or adenocarcinoma received concurrent cisplatin and fluorouracil (as in RTOG 8501),r but they were randomly assigned to one of two different RT doses: 50.4Gy (28 fractions of 1.8Gy each, five fractions per week) or 64.8Gy (36 fractions of 1.8Gy each, five fractions per week). Higher RT doses were not associated with a higher median (13 versus 18 months) or two-year survival (31% versus 40%), or the incidence of locoregional persistent or recurrent disease (56% versus 52% for the high dose and control groups, respectively). High-dose RT was significantly more toxic.
There have been no randomised comparisons between definitive chemoradiotherapy and surgery alone in resectable oesophageal cancer. In SCC, the addition of surgery to induction CRT improved local control but not survival.rr
Honing et alr compared survival and toxicity for patients receiving definitive chemoradiation with either cisplatin/fluorouracil (n=47) or carboplatin/paclitaxel (n=55). Overall survival was not different between the two groups. Median disease free survival was also comparable. A higher percentage of patients were able to complete the carboplatin/paclitaxel regimen (82% vs. 57%, P=0.01). Patients in this group also recorded significantly lower haematological and non-haematological toxicity (>grade 3); 4% and 18% vs 19% and 38% (P=0.001) in the cisplatin/fluorouracil group.r