Long-term result of a multi-institutional phase II chemoradiation therapy trial for esophageal cancer using daily low-dose 5-fluorouracil and cis-diamminedichloro-platinum

Abstract

Treatment results of chemoradiation therapy for esophageal cancer are almost comparable to those of surgery. Most regimens of chemoradiation therapy consist of radiation and standard-dose combination chemotherapy. However, standard-dose chemotherapy causes a relatively high incidence of hematological adverse effects and therefore, patients can receive the chemotherapy only once or twice during the radiation course. On the other hand, reduced-dose chemotherapy can be given throughout the radiation course and can sensitize the response of tumor to radiation. We conducted a multi-institutional phase U clinical trial to investigate the efficacy of concurrent low-dose chemotherapy (5-FLUOROURACIL (5FU) and cis-diamminedichloro-platinum (CDDP)) and radiotherapy for esophageal cancer. The aim of this study was to evaluate the long-term results and late toxicity of the trial. From 1994 to 2001, 68 patients with inoperable esophageal cancer were registered in this study. The eligibility criteria were as follows: age <80; ECOG performance Status: 0,1,2, or 3; no distant metastasis (except for supraclavicular lymph nodes); no previous treatment; no other active malignancy; and no organ dysfunction. Radiotherapy was performed by standard fractionation using 6- or 10-MV x-ray. The initial radiation fields included the primary lesion, thoracic and cervical esophagus, and mediastinal and supraclavicular lymph nodes (T-shaped field) for the cervical and upper thoracic esophagus, and the primary lesion, thoracic esophagus, and mediastinal and perigastric lymph nodes (long L-shaped field) for the middle and lower thoracic esophagus. After administration of 46 Gy, the fields were reduced to boost oblique fields to exclude the spinal cord from the field. Total radiation dose ranged from 60 Gy to 70 Gy. The daily dose of 5FU was 250 mg/m2 (continuous infusion) and the dose of CDDP was 3 mg/m2. These chemotherapy agents were administered for at least 5 weeks. Sixty-four patients (94%) received a radiation dose of 60 Gy or more and 48 patients (71%) received chemotherapy for 5 weeks or more. The follow-up period of surviving patients ranged from 17 to 114 months. The 2-year and 5-year overall survival rates were 41% and 19%, respectively. Survival rates were statistically different between T4/non-T4, N0/N1, StageUVW, and CR/non-CR. Overall treatment time was not a predictive factor. Although grade 3 leukopenia, anemia, and thrombocytopenia were observed in 11, 1, and 2 patients, respectively, there was no grade 4 hematological toxicity. Non-hematological toxicities (grade 3:grade 4) were esophagitis (9:2), appetite loss (19:1), nausea (0:4) and liver dysfunction (3:0). One patient died suddenly during the treatment, possibly due to cardiac accident. Three patients died because of late cardiac toxicity. Thirty-nine patients recurred. Twenty-nine patients (74%) had loco-regional recurrence and 10 patients (26%) showed recurrence out of the radiation field without loco-regional recurrence. These treatment results are comparable to those of standard-dose chemoradiotherapy with less toxicity. A prospective randomized trial to compare the standard- and reduced-dose chemoradiotherapy regimens is warranted.