Randomized phase 2 study of subcutaneous amifostine versus epoetin-α given 3 times weekly during concurrent chemotherapy and hyperfractionated radiotherapy for limited-disease small cell lung cancer

BACKGROUND. The purpose of the current study was to investigate the role of amifostine and epoetin-alpha in reducing severe toxicities during Concurrent chemo-hyperfractionated radiotherapy (CCRT) for limited disease small cell lung cancer (LD-SCLC). METHODS. Seventy-six patients with LD-SCLC were enrolled. The treatment schedule was consisted of two 28-day cycles of cisplatin at a dose of 30 mg/m(2) (Days 1 and 8) and irinotecan at a dose of 60 mg/m(2) (Days 1, 8, and 15) followed by two 21-day cycles of cisplatin at a dose of 60 mg/m(2) (Day 1) and etoposide at a dose of 100 mg/m(2) (Days 1-3) With concurrent twice-daily thoracic radiotherapy for a total of 45 grays. Patients were randomly assigned at registration to either amifostine at a dose of 500 mg or epoetin-alpha at a dose of 10,000 IU subcutaneously 3 times weekly (n = 36 patients and 40 patients, respectively). Fifteen of 36 patients assigned to the amifostine arm did not receive amifostine because of a lack of supply. RESULTS. Amifostine treatment was associated with higher febrile neutropenia (P =.003) and grade 2 or 3 nausea (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) (P =.03). It also demonstrated a trend toward higher grade 4 leukopenia (P =.05). Grade 3 esophagitis was reported in 30% of patients treated with amifostine and 9% of patients treated with epoetin-alpha (P =.059). Epoetin-a treatment was associated with less grade 2 or 3 anemia (P =.031) and lower decreases in hemoglobin level during CCRT (P =.016). The median survival times for both treatment arms were comparable (22.6 months in the amifostine arm vs 25.6 months in the epoetin-alpha arm; P =.447). CONCLUSIONS. Although amifostine administered 3 times weekly during CCRT did not significantly reduce severe toxicities, epoetin-alpha was effective in preventing severe anemia during CCRT in patients with LD-SCLC. Other radioprotective strategies to minimize severe toxicities should be investigated.