Combined modality therapy for esophageal carcinoma: preliminary results from a large Australasian multicenter study

This report updates local control and survival experience and focuses on treatment toxicity in 294 patients with esophageal cancer who have been treated at six Australasian centers using three prospective unrandomized protocols that used concurrent radiation, cisplatin, and modest dose infusional fluorouracil.

Protocol 1--"definitive" chemoradiation. One hundred and thirty-seven patients have been treated with "definitive" radiation to 60 Gy in 6 weeks plus two courses of cisplatin (80 mg/m2) and infusional fluorouracil (800 mg/m2/day over 4 days) during the first and fourth weeks of radiation. Protocol 2--"preoperative" chemoradiation and surgery. Seventy-eight patients received chemoradiation using the same chemotherapy, but 30-35 Gy in 3-4 weeks prior to surgery. Protocol 3--"palliative" chemoradiation. Seventy-nine patients deemed incurable were treated "palliatively" with the same chemoradiation protocol without surgery. Follow-up ranges from 6 months to 7 years (mean 22 months) in live patients.

Durable palliation of dysphagia in all three treatment groups has been reflected by encouraging 3-year survival expectations of 43.2 +/- 5% in definitively treated patients, 40.3 +/- 7.65% in surgically treated patients, and 8.5% +/- 3.9% in the palliatively treated patients. There are early indications that female patients have fared better than males. Toxicity levels were modest in all three groups. Following definitive treatment, severe myelotoxicity (World Health Organization grades 3 and 4) occurred in 19%, severe esophagitis (World Health Organization grade 3) in 11%, and moderate or severe benign stricture in 17%, depending upon age and sex of the patient (being worse in female patients).

These studies demonstrate that the concurrent addition of modest dose cisplatin and infusional dose fluorouracil to radiation in the definitive, preoperative, and palliative settings contribute to high rates of durable dysphagia-free survival, with overall survival comparable to (and possibly better than) the chemoradiation arm of the recently reported Intergroup Study, but at the cost of less morbidity.