Randomized phase 2 study of subcutaneous amifostine versus epoetin-alpha 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/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-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-alpha 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.
Han
Hye-Suk
HS
Lung Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
Han
Ji-Youn
JY
Yu
Sun Young
SY
Pyo
Hong Ryull
HR
Kim
Hyae Young
HY
Cho
Kwan Ho
KH
Lee
Dae Ho
DH
Kim
Heung Tae
HT
Lee
Jin Soo
JS
D000368:Aged; D004999:Amifostine / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D011994:Recombinant Proteins; D016019:Survival Analysis
D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D004999:Amifostine