NEOADJUVANT CHEMOTHERAPY AND HYPERFRACTIONATED RADIOTHERAPY WITH CONCURRENT LOW-DOSE CHEMOTHERAPY FOR SQUAMOUS-CELL ESOPHAGEAL-CARCINOMA

Purpose: We conducted a prospective study of neoadjuvant treatment for squamous cell carcinoma of the esophagus, modifying the chemotherapy protocol by adding l-folinic acid and giving bifractionated radiothera py with a cis-diaminedichloroplatinum (CDDP) injection before each fra ction. Methods and Materials: Thirty-two patients, 30 men, 2 women, me an age 56.2 +/- 8.9 years, with resectable squamous cell carcinoma of the esophagus (TNM stage I = 4, IIA = 4, IIB = 13, III = 11) ere inclu ded. Chemotherapy, CDDP (80 mg/m(2) D2), 5-fluorouracil (5-FU; 600 mg/ m(2), D1-4), and l-folinic acid (200 mg/m(2), D1-4), was given in two sessions with a 3-week interval during which the patients received rad iotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg in jection of CDDP was given prior to each fraction. Patients underwent s urgery 4 to 7 weeks after neoadjuvant therapy. Results: No severe side effects were observed in 12 patients. Grade 3 effects (WBC, platelets , mucositis) occurred in 16 patients and grade 4 effects (platelets, m ucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tum ors (81%). Operative mortality was 10%. The 26 surgical specimens show ed complete response (n = 18), persistent microscopic residues (n = 4) , or not significant modification (n = 4). Survival at 1, 2, and 3 yea rs was 81, 61, and 51.6% and disease-free survival was 75, 59, and 54% respectively. Conclusions: This new therapeutic combination is aggres sive and associated with a high postoperative mortality but has a rema rkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 3-year survival reached 52%, a v ery high rate in our experience. (C) 1998 Elsevier Science Inc.