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 radiotherapy with a cis-diaminedichloroplatinum (CDDP) injection before each fraction. Methods and Materials: Thirty-two patients, 30 men, 2 women, mean age 56.2 ± 8.9 years, with resectable squamous cell carcinoma of the esophagus (TNM stage I = 4, IIA = 4, IIB = 13, III = 11) were included. 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 radiotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg injection of CDDP was given prior to each fraction. Patients underwent surgery 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, mucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative mortality was 10%. The 26 surgical specimens showed complete response (n = 18), persistent microscopic residues (n = 4), or not significant modification (n = 4). Survival at 1, 2, and 3 years was 81, 61, and 51.6% and disease-free survival was 75, 59, and 54% respectively. Conclusions: This new therapeutic combination is aggressive and associated with a high postoperative mortality but has a remarkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 3-year survival reached 52%, a very high rate in our experience.