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.

Abstract

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.

• Authors: Hye-Suk Han, Ji-Youn Han, Sun Young Yu, Hong Ryull Pyo, Hyae Young Kim, Kwan Ho Cho, Dae Ho Lee, Heung Tae Kim, Jin Soo Lee
• Journal: Cancer (Cancer) Vol. 113 Issue 7 Pg. 1623-31 (Oct 01 2008) ISSN: 0008-543X [Print] United States
• PMID: 18671241 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Radiation-Protective Agents
• Recombinant Proteins
• Erythropoietin
• Epoetin Alfa
• Amifostine

Topics

• Aged
• Amifostine (administration & dosage)
• Antineoplastic Agents (adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Carcinoma, Small Cell (drug therapy, radiotherapy)
• Combined Modality Therapy
• Dose Fractionation, Radiation
• Drug Administration Schedule
• Epoetin Alfa
• Erythropoietin (administration & dosage)
• Female
• Humans
• Injections, Subcutaneous
• Lung Neoplasms (drug therapy, radiotherapy)
• Male
• Middle Aged
• Radiation-Protective Agents (administration & dosage)
• Recombinant Proteins
• Survival Analysis