Concurrent Oxaliplatin, 5-Fluorouracil, and Radiotherapy in the Treatment of Locally Advanced Esophageal Carcinoma

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Abstract

Purpose:

The combination of oxaliplatin, 5-fluorouracil, and leucovorin with concurrent radiotherapy was demonstrated to be a safe regimen for locally advanced esophageal carcinoma in a prior phase I study. We now report the efficacy data for 42 patients treated with this regimen.

Methods:

Each chemotherapy cycle lasted 29 days and consisted of 5-fluorouracil, 180 mg/m2 protracted-infusion from days 1 to 29, and oxaliplatin, 85 mg/m2 on days 1, 15, and 29. The first cycle was administered concurrently with radiation. The radiation field included regional lymph nodes as well as the primary tumor or tumor bed to a dose of 50.4 Gy in 28 fractions. After concurrent chemoradiotherapy, 1 to 2 additional cycles of chemotherapy were administered. If esophagectomy was indicated, it occurred 4 weeks after completion of concurrent chemoradiotherapy. In the adjuvant group, concurrent chemoradiotherapy was initiated 4 weeks after surgery.

Results:

Median age was 61 years (range 38–78 years); 30 (71%) of the patients were male. Thirty-three patients had adenocarcinoma, and 9 had squamous cell carcinoma. Concurrent chemoradiotherapy was administered preoperatively (group 1) in 24 patients, definitively (group 2) in 13 patients, and as adjuvant treatment (group 3) in 5 patients. In group 1, 16 patients were down-staged including 1 patient with minimal residual disease and 5 with a complete pathologic response; 4 patients were not down-staged, and 4 did not undergo esophagectomy (2 progressed, 1 died of unrelated causes, and 1 refused). In group 2, 1 patient had a complete clinical response, 4 others were down-staged, 2 had stable disease, and 6 progressed. Four patients in group 3 progressed. Median survival was 28 months for group 1, 12 months for group 2, and not reached at 14 months for group 3. There was one grade 4 toxicity (anaphylaxis) in group 2. Grade 3 toxicities were reported for 5 patients in group 1 and 1 patient in group 2. They consisted of hypotension (n = 1), fatigue (n = 2), diarrhea (n = 2), neuropathy (n = 1), mucositis (n = 1), pneumonitis (n = 1), dehydration (n = 1), emesis (n = 1), and weight loss (n = 1).

Conclusions:

Our study supports the incorporation of oxaliplatin into a multimodal concurrent chemoradiotherapy protocol for locally advanced esophageal cancer.

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