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

• Published in: Cancer 2008-10, Vol.113 (7), p.1623-1631
• Main Authors: Han, Hye‐Suk, Han, Ji‐Youn, Yu, Sun Young, Pyo, Hong Ryull, Kim, Hyae Young, Cho, Kwan Ho, Lee, Dae Ho, Kim, Heung Tae, Lee, Jin Soo
• Format: Article
• Language: English
• Subjects: Aged; amifostine; Amifostine - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Carcinoma, Small Cell - drug therapy; Carcinoma, Small Cell - radiotherapy; Combined Modality Therapy; concurrent chemoradiotherapy; Dose Fractionation; Drug Administration Schedule; Epoetin Alfa; epoetin‐α; Erythropoietin - administration & dosage; Female; Humans; Injections, Subcutaneous; Lung Neoplasms - drug therapy; Lung Neoplasms - radiotherapy; Male; Medical sciences; Middle Aged; Pneumology; Radiation-Protective Agents - administration & dosage; Recombinant Proteins; small cell lung cancer; Survival Analysis; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.23790

BACKGROUND. The purpose of the current study was to investigate the role of amifostine and epoetin‐α 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/m2 (Days 1 and 8) and irinotecan at a dose of 60 mg/m2 (Days 1, 8, and 15) followed by two 21‐day cycles of cisplatin at a dose of 60 mg/m2 (Day 1) and etoposide at a dose of 100 mg/m2 (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‐α 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‐α (P = .059). Epoetin‐α 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‐α arm; P = .447). CONCLUSIONS. Although amifostine administered 3 times weekly during CCRT did not significantly reduce severe toxicities, epoetin‐α was effective in preventing severe anemia during CCRT in patients with LD‐SCLC. Other radioprotective strategies to minimize severe toxicities should be investigated Cancer 2008. © 2008 American Cancer Society. The role of amifostine and epoetin‐α to reduce severe toxicities during concurrent chemo‐hyperfractionated radiotherapy (CCRT) was investigated for limited‐disease small cell lung cancer (LD‐SCLC). A total of 76 chemotherapy‐naive patients with LD‐SCLC were randomly assigned at registration to either amifostine or epoetin‐α. Although amifostine during CCRT did not significantly reduce severe toxicities, epoetin‐α was found to be effective in preventing severe anemia during C