Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial

Eur J Surg Oncol. 2003 Sep;29(7):580-7. doi: 10.1016/s0748-7983(03)00111-2.

Abstract

Background: Neither postoperative radiotherapy nor chemotherapy alone provided a survival benefit after curative esophagectomy for esophageal squamous carcinoma.

Material and methods: Of 103 consecutive patients who underwent potentially curative esophagectomy for esophageal squamous carcinoma, 45 patients with advanced cancers without preoperative adjuvant treatments were prospectively randomized to two groups; postoperative chemotherapy alone (Group A, n=23) and postoperative radio/chemotherapy (Group B, n=22). In Group A, cisplatin (CDDP) (50 mg/m(2)) was given by intravenous infusion on days 1 and 15, and 5-fluorouracil (5-FU) (300 mg/m(2)) was given daily by continuous intravenous infusion for 5 weeks. In Group B, in addition to the same chemotherapeutic regimen of Group A, 50 Gy of radiotherapy was given to the mediastinum over 5 weeks. The immunohistochemical staining of tumoral p53 and microvessel density was undertaken to correlate to the radio/chemosensitivity.

Results: There were no significant differences in the clinicopathologic characteristics between the two groups. The median dose of 5-FU and CDDP administered were not significantly different between the two groups. The mean (SD) dose of radiotherapy in Group B was 42+10 Gy. The 1-, 3- and 5-year survival rates in Group A were 100, 63 and 38% and those in Group B were 80, 58 and 50%, respectively (P=0.97). In each group, four patients succumbed to locoregional recurrences. Tumoral p53 was immunohistochemically negative in 43% in Group A and 77% in Group B (P=0.03), indicating that many patients in Group B might be potentially sensitive to radiochemotherapy. The 3- and 5-year survival rates (75 and 64%) of patients with p53 negative expression (n=18) were significantly (P=0.03) better than those with p53 positive expression (n=27, 44 and 26%). The long-term survival was better for patients with p53 negative tumours than those with p53 positive tumours in Group B (P=0.06 by long-rank test, P<0.05 by Generalized-Wilcoxon test). However, the long-term survival was not different between the patients who had p53 negative and positive tumours in Group A (P=0.19). These data suggest that there were no survival advantage for patients receiving radiotherapy in Group B, instead p53 negative tumours appeared to have a favorable prognosis.

Conclusion: Postoperative radiotherapy administered concurrently with chemotherapy does not provide a survival benefit compared with chemotherapy alone. Tumoral p53 expression has a predictive value for survival in patients treated with postoperative radio/chemotherapy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Chemotherapy, Adjuvant / adverse effects
  • Cisplatin / administration & dosage
  • Drug Administration Schedule
  • Esophageal Neoplasms / blood supply
  • Esophageal Neoplasms / chemistry
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / radiotherapy*
  • Esophageal Neoplasms / surgery
  • Esophagectomy*
  • Female
  • Fluorouracil / administration & dosage
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Microcirculation
  • Middle Aged
  • Mutation
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neovascularization, Pathologic / diagnosis*
  • Postoperative Period
  • Predictive Value of Tests
  • Prospective Studies
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant / adverse effects
  • Survival Analysis
  • Thorax
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / analysis*

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Protein p53
  • Cisplatin
  • Fluorouracil