Palliation of dysphagia associated with advanced esophageal cancer can be effectively accomplished with radiotherapy alone, without the addition of chemotherapy, according to a multinational phase III study presented at the 2015 Gastrointestinal Cancers Symposium.1
“There was no significant improvement in dysphagia when chemotherapy was added to radiotherapy. The trial was not powered to show equivalence and thus is a negative trial,” said Michael Gordon Penniment, MD, of Royal Adelaide Hospital in Australia. “Radiotherapy alone remains an excellent tool for palliation of [dysphagia in] patients with advanced esophageal cancer and should remain the standard of care.”
The conclusion, however, was questioned by some specialists, including David Ilson, MD, of Memorial Sloan Kettering Cancer Center, New York (see sidebar).
Study Details
TROG 03.01 NCIC CTG ES2 was conducted in the United Kingdom, Canada, Australia, and New Zealand and therefore reflects practice in several countries, Dr. Penniment said. The study included 220 patients, who were randomized to receive either palliative radiotherapy (35 Gy in 15 fractions or 30 Gy in 10 fractions) or the same with chemotherapy (cisplatin 80 mg/m2 on day 1 or 20 mg/m2 on days 1–4 plus fluorouracil 800 mg/m2/day on days 1–4). Baseline parameters, including proportion with metastatic disease (approximately 73%) and performance status, were similar.
The study’s primary endpoint was relief of dysphagia, defined as an improvement of at least one point on the Mellow scale at 9 weeks and at 4 weeks thereafter. The researchers hypothesized that chemotherapy would add 15% to the dysphagia response to radiotherapy alone.
“A response required improved swallowing 9 weeks after starting radiotherapy, maintained until week 13,” he explained.
No Differences Observed
There were no significant differences between the two treatment arms for dysphagia, progression-free survival, or overall survival, Dr. Penniment reported.
Patients receiving radiotherapy alone had a dysphagia response rate of 68%, which was maintained in 42% of patients. The response to chemoradiotherapy was 74%, which was not a significant difference (P = .34) vs radiotherapy alone, and this was maintained in 47% (P = .43). The 15% difference in the primary endpoint was not met, he noted.
Median overall survival was 203 days for the radiotherapy arm and 210 days for the chemoradiotherapy arm. “There was no difference and no trend for chemoradiotherapy vs radiotherapy alone. These overall survival curves are the same,” he indicated.
“Although the results of the trial showed equally poor survival prognosis in both arms, 21 patients were still alive 2 years post treatment, and a large percentage of these patients had metastatic disease,” he said.
He commented, “Survival beyond 1 year was something of a surprise…. There’s a group of patients who, though palliative, with active oncologic care might actually be surviving beyond 1 year.”
Although survival outcomes were similar, patients receiving chemoradiotherapy experienced more toxicity, especially more nausea (P < .01) and vomiting (P < .01). In a quality-of-life analysis, no significant differences were observed. In the dysphagia domain, improvements were noted for 50% of the chemoradiotherapy arm and 64% of the radiotherapy arm; the median time to improvement was 2.6 and 2.3 months, respectively.
Dr. Penniment indicated that 33 patients in the radiotherapy arm did receive chemotherapy as well “somewhere in their journey,” usually not because they became symptomatic. “But two-thirds of the radiotherapy arm never got chemotherapy and had good symptom control,” he noted.
“Two of my patients getting radiotherapy alone were among those still alive and well at 2 years,” he continued. “We are looking at data to see if we can predict that group. We are confident there will be a group of patients who can get by with less treatment than 3 weeks of radiotherapy plus or minus chemotherapy and a group needing more or something different.” ■
Disclosure: Dr. Penniment reported no potential conflicts of interest.
Reference
1. Penniment MG: A full report of the TROG 03.01 NCIC CTG ES2 multinational phase III study in advanced esophageal cancer comparing palliation of dysphagia and quality of life in patients treated with radiotherapy or chemoradiotherapy. 2015 Gastrointestinal Cancers Symposium. Abstract 06.
