Treating Esophageal Cancer With Preoperative Chemoradiotherapy

Phase 3 study demonstrates that neo-adjuvant chemoradiotherapy plus surgery, in esophageal or esophago-gastric-junction carcinoma, results in a higher survival rate than surgery treatment alone.

Esophageal cancer, the eighth-most prevalent cancer globally, causes over 400,000 deaths annually with the 5-year survival rate rarely exceeding 40%. Esophageal adenocarcinoma incidence continues to rise while squamous-cell carcinoma incidence rates have stayed steady.

During 2004-2008, clinical investigators studied the efficacy of surgery with or without neo-adjuvant chemoradiotherapy in various esophageal cancers. Neo-adjuvant therapy is the treatment administered before the definitive treatment, which in this case was surgery.

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The trial enrolled patients aged 18 to 75 years, diagnosed with squamous-cell carcinoma, adenocarcinoma or large-cell undifferentiated carcinoma of the esophagus or esophagogastric junction i.e. the junction between the stomach and the esophagus. The cancers had not spread to distant organs. In addition, patients had ≤ 2 WHO performance status scores with ≤ 10% weight loss and no prior radiotherapy or chemotherapy experience.

Of the 368 enrolled patients, 188 patients with resectable tumors were randomly assigned to receive surgery alone while 178 patients received 5 weeks of carboplatin, paclitaxel and concurrent radiotherapy followed by surgery. Dexamethasone, clemastine, ranitidine and standard antiemetic agents were administered to all patients.

Surgery-only patients were operated soon after post-randomization Chemoradiotherapy patients underwent surgery within 4 to 6 weeks of chemoradiotherapy completion.

The table below provides the overall survival rates in the two treatment groups:

The pathological assessment revealed that complete tumor resection was attained in 92% patients in the chemoradiotherapy–surgery versus 69% patients in the surgery-only group. Complete pathological response was observed in 29% patients who underwent resection after chemoradiotherapy.

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Post-treatment years	Chemoradiotherapy-surgery patients	Surgery only group
1	82%	70%
2	67%	50%
3	58%	44%
5	47%	34%

The pathological assessment revealed that complete tumor resection was attained in 92% patients in the chemoradiotherapy–surgery versus 69% patients in the surgery-only group. Complete pathological response was observed in 29% patients who underwent resection after chemoradiotherapy.

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Common adverse events included reduced white blood cell counts, anorexia (5%) and fatigue (3%). The pre-surgery chemoradiotherapy resulted in more but acceptable high-grade toxic events. Postoperative complications and in-hospital mortality were similar in both treatment groups.

Thus, patients with cancers at the esophagus or the junction of the stomach and the esophagus experience a substantial increase in overall survival when treated before surgery with carboplatin-paclitaxel-radiotherapy combination.

Reference: Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer; Van Hagen et al; N Engl J Med 2012; 366:2074-2084

Source-Medindia