Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non–small-cell lung cancer: report of a randomized comparative trial☆

Abstract 

Purpose

To determine the ability of amifostine to reduce the severity and/or incidence of the acute toxicities of concurrent chemotherapy and radiotherapy (RT) for non–small-cell lung cancer.

Methods and materials

Patients with inoperable, nonmetastatic non–small-cell lung cancer receiving concurrent chemoradiotherapy were randomized to one of two treatment groups. Arm 1 patients received thoracic RT (total dose, 69.6 Gy in 58 fractions of 1.2 Gy b.i.d. 5 d/wk), plus oral etoposide (50 mg b.i.d. 30 min before thoracic RT for 10 days, repeated on Day 29) and cisplatin (50 mg/m² i.v. on Days 1, 8, 29, and 36). Arm 2 patients received the same treatment plus amifostine (500 mg i.v. 20–30 min before any treatment the first 2 days of each week). Acute effects were assessed using the National Cancer Institute Common Toxicity Criteria.

Results

Sixty-two patients were enrolled between November 1998 and January 2001. The minimal follow-up was 24 months, and the median follow-up of living patients was 31 months. The patient and tumor characteristics were equally distributed between the patients in the two arms. The median survival time was 20 months in Arm 1 patients and 19 months in Arm 2 patients. The maximal esophageal toxicity was mild (Grade 1) in 23%, moderate (Grade 2) in 42%, and severe (Grade 3-4) in 35% of patients in Arm 1; the corresponding rates for the Arm 2 patients were 48%, 35%, and 16% (p = 0.021). Severe pneumonitis occurred in 16% of the Arm 1 and none of the Arm 2 patients (p = 0.020, chi-square test). Neutropenic fever occurred in 39% of Arm 1 and 16% of Arm 2 patients (p = 0.046, chi-square test). Mild hypotension, dysgeusia, and sneezing were significantly more frequent among the patients in Arm 2.

Conclusion

Amifostine reduced the severity and incidence of acute esophageal, pulmonary, and hematologic toxicity resulting from concurrent cisplatin-based chemotherapy and RT. Amifostine had no apparent effect on survival in these patients with unresectable non–small-cell lung cancer, suggesting that it does not have a tumor-protective effect.

Keywords:  Cytoprotection, Non–small-cell lung cancer, Randomized controlled trial