Preliminary Results of Intergroup INT 0123 Randomized Trial of Combined Modality Therapy (CMT) for Esophagel Cancer: Standard vs. High Dose Radiation Therapy
Theodore Robnett, MD
OncoLink Assistant Editor
Last Modified: May 20, 2000
Presenter: B.D. Minsky
Affiliation: RTOG, ECOG, NCCTG, others
Although definitive chemoradiation for esophageal cancer is a relatively good treatment option for patients with non-metastatic disease, survival rates remain disappointing. This intergroup trial tests the dose escalation hypothesis in this population receiving chemoradiation. Concerns regarding high dose radiation therapy in esophageal cancer stem from potentially increased toxicity to important nearby structures: heart and associated vessels, trachea, lungs, and spinal cord.
Materials and Methods:
- Eligibility for randomization: Biopsy proven, any histology, cT1-4NXM0. Tumors within 2cm of the stomach (gastroesophageal junction) were excluded, as the stomach would not tolerate high dose RT. KPS >= 60, tumor at the carina required bronchoscopy, and those patients with tracheoesophageal fistula were excluded.
- Identical chemotherapy on both arms: concurrent 5-FU (1000 mg/m2 x 96 hours) and cisplatin bolus (75 mg/m2) on weeks 1 and 5 of radiation therapy, and 1 and 5 weeks after finishing radiation therapy.
- Standard dose of radiation therapy: 50.4 Gy. High dose of radiation therapy: 64.8 Gray.
- 236 patients were accrued, 216 were eligible. The study was closed prior to its accrual goal after an interim analysis showed a 2.4% survival result favoring the high dose arm. 108 patients were on each arm.
- 3% and 4% major protocol deviations from RT in the hi dose and low dose arms, respectively.
- Median survival in standard dose arm: 17.5 months. High dose arm: 12.9 months. 2 year actuarial survival in standard dose arm: 38%. High dose arm: 29%.
- Eleven treatment-related deaths (deaths during treatment) occured in the high dose arm, but only 3 of these were seen during the high dose portion of treatment (dose > 50.4 Gy). Two treatment-related deaths were seen in the low dose arm.
- Grade 4 and grade 1,2, and 3 toxicities were seen in 26 and 43 patients in the high dose arm, respectively. In the standard arm, Grade 4 and sub-grade 4 toxicities were seen in 31 and 33 patients, respectively.
- High dose radiation as part of combined modality therapy may produce excessive toxicity with no proven benefit. This toxicity might be avoided by careful patient selection and appropriate treatment planning, however the possible effects of high dose radiation therapy such as fistula formation, pneumonitis, and cardiac damage should not be taken lightly.
- The use of "high dose" radiation as part of definitive treatment for esophageal cancer should be carefully considered outside of clinical trials.
Differences Between Abstract and Presentation:
- The number of eligible patients were different in the abstract and oral presentation: abstract: 196, 216 (as in #1 above).
- Nine treatment-related deaths were mentioned in the abstract, 11 in the oral presentation.
- Two year overall survivals were slightly different: standard RT 33%, high dose RT 29% in the abstract. Oral presentation, as in #3 above.
- In chemoradiation for esophageal cancer, 64.8 Gray offers no survival or control benefit over 50.4 Gray.
- The authors conclude that excess toxicity deaths do not appear to be related to the high dose of radiation therapy delivered, because only 3 deaths occurred during the high dose portion of therapy.