Randomized Phase III Trial of Radiation +/- Amifostine in Patients with Advanced Stage Lung Cancer

Jacqui Tan, MD
OncoLink Assistant Editor
Last Modified: November 1, 1999

Presenter: Antonadou D
Affiliation: Hellenic Group Clinical-Radiation Oncology, Greece

Summary:
Pneumonitis and esophagitis are two of the most problematic adverse effects associated with thoracic irradiation. Severe symptoms can cause patient distress and may necessitate treatment delays or possibly premature termination. This, in turn, could theoretically affect clinical outcome. Amifostine is a radioprotective drug which might reduce these toxicities.

Methods:

This phase III multicenter trial randomized 146 patients with stages II-IV lung cancer to receive 55-60 Gy thoracic irradiation with or without daily pre-treatment amifostine (340 mg/m2 IV).
Endpoints included acute and chronic pneumonitis, acute esophagitis, and loco-regional response. RTOG scoring criteria were used to score the toxicities.

Results:

The authors report that patients randomized to receive amifostine had a statistically significant improvement in the incidence of clinical and radiographic pneumonitis (19% vs. 52% at 3 months after radiation).
Patients on the amifostine arm also had a lower incidence of acute esophagitis (5% vs. 30% at week 6 of treatment).
No difference in clinical response was seen between the two arms (75% vs. 76%).

Clinical/Scientific Implications:

One concern raised at the presentation was whether the rate of pneumonitis in the control arm was unusually high. This might have been due to the authors reporting grade 2 or higher toxicity, as opposed to grade 3 in many other studies.
Another issue was that patients did not generally receive concurrent chemotherapy, a practice which is becoming more prevalent.
Amifostine may still prove to be an important aid in the delivery of thoracic radiation.
The RTOG is currently conducting a similar phase III trial using radiation therapy and chemotherapy, and these results are eagerly anticipated.

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