Late course accelerated hyperfractionated radiotherapy plus concurrent chemotherapy for squamous cell carcinoma of the esophagus: a phase III randomized study.

PURPOSE: Late course accelerated hyperfractionated (LCAF) radiotherapy (RT) is as effective as standard chemoradiotherapy for nonsurgical management of locally advanced esophageal squamous cell carcinoma (SCC). We have evaluated further the efficacy of concurrent LCAF RT and chemotherapy. METHODS AND MATERIALS: In all, 111 eligible patients with esophageal SCC were randomized to receive LCAF alone (LCAF) or concurrent LCAF and chemotherapy (LCAT+CT) between March 1998 and July 2000. All patients received conventional fractionation irradiation of 1.8 Gy per day, to a dose of 41.4 Gy/23 fractions in 4-5 weeks, followed by accelerated hyperfractionated irradiation using reduced fields, 1.5 Gy/fractions twice a day, to a dose of 27 Gy in 18 days. Thus, the total dose was 68.4 Gy/41 fractions in 44 days. Fifty-four patients in the LCAF+CT arm had an additional four cycles of chemotherapy using cisplatin 25 mg/m(2) daily and fluorouracil (5-FU) 600 mg/m(2) daily on Days 1-3 every 4 weeks starting on the same day that LCAF was delivered. RESULTS: The median survival was 23.9 months (95% confidence [CI], 20.1-27.7) for the LCAF arm and 30.8 months (95% CI, 17.6-44.1) for the LCAF+CT arm, respectively. Survival rates at 1, 3, and 5 years of the LCAF arm were 77%, 39%, and 28%, respectively, while those of the LCAF+CT arm were 67%, 44%, and 40%, respectively (p = 0.310). Grades 3 and 4 acute toxicities occurred in 46% and 25% of the patients in the LCAF arm and the LCAF+CT arm, respectively; 6% of the patients in the combined arm had Grade 5 acute toxicities, whereas none was noted in the LCAF alone arm. CONCLUSIONS: Late course accelerated hyperfractionation was effective for locally advanced esophageal SCC. There was a trend toward better survival among patients who received intensified treatment with concurrent chemotherapy. Further randomized studies with a larger number of patients should be carried out, but additional measures must be taken to reduce the higher mortality rate due to chemotherapy-related acute toxicities.

Comparison between continuous accelerated hyperfractionated and late-course accelerated hyperfractionated radiotherapy for esophageal carcinoma.

PURPOSE: To compare the treatment results and toxicity of continuous accelerated hyperfractionated (CAHF) and late-course accelerated hyperfractionated (LCAF) radiotherapy (RT) for esophageal carcinoma. METHODS AND MATERIALS: Between August 1996 and March 1999, 101 patients with squamous cell carcinoma of the esophagus were randomized into two groups: 49 to the CAHF group and 52 to the LCAF group. Patients in the CAHF group received RT at 1.5 Gy/fraction b.i.d. (6-h interval), 5 d/wk, to a total dose 66 Gy in 44 fractions during 4.4 weeks. The patients in the LCAF group received conventional fractionation RT, 1.8 Gy/fraction, to a dose of 41.4 Gy in 23 fractions during 4.6 weeks, followed by accelerated fractionation RT using reduced fields, b.i.d., at 1.5 Gy/fraction, with a minimal interval of 6 h between fractions. The total dose was 68.4 Gy in 41 fraction during 6.4 weeks. Patient age, gender, performance score, diet, lesion location, lesion length, stage, and fractionation (CAHF or LCAF) were entered into the univariate and multivariate analyses. RESULTS: All patients finished the treatment course, except for 1 patient in the CAHF group because of severe acute esophagitis. The rate of Grade I, II, and III acute bronchitis was 18.4% (9 of 49), 30.6% (15 of 49), and 8.2% (4 of 49) in the CAHF group and 13.5% (7 of 52), 21.2% (11 of 52), and 3.8% (2 of 52) in the LCAF group, respectively. However, the difference between the two groups was not statistically significant (p = 0.084). The rate of Grade I, II, III, and IV acute esophagitis was 6.1% (3 of 49), 32.7% (16 of 49), 46.9% (23 of 49), and 14.3% (7 of 49) in the CAHF group and 26.9% (14 of 52), 32.7% (17 of 52), 7.7% (4 of 52), and 1.9% (1 of 52) in the LCAF group, respectively. The difference was statistically significant (p < 0.001). The local control rate at 1, 2, and 3 years was 88.7%, 83.9%, and 55.9% in the CAHF group and 80.7%, 71.4%, and 57.1% in the LCAF group, respectively (p = 0.1251). The 1-, 2-, and 3-year survival rate was 79.6%, 51.6%, and 37.6% in the CAHF group and 80.0%, 57.6%, and 41.2% in the LCAF group, respectively (p = 0.5757). Multivariate analysis showed that age and lesion length were independent significant prognostic factors for local control rate, and age was for the overall survival rate. The fractionation schedule had no significant prognostic effect. CONCLUSION: CAHF and LCAF result in similar 1-, 2-, and 3-year local control and survival rates. CAHF resulted in more severe acute esophagitis and may be less well tolerated than LCAF. The treatment results after the CAHF and LCAF regimens were better than those of historical conventional RT.