Randomized Phase III Study of Amifostine in Patients Treated with Chemoradiation for Inoperable Stage II-III Non-Small Cell Lung Cancer (NSCLC)

William Levin, MD
University of Pennsylvania Cancer Center
Last Modified: November 4, 2001

Presenter: R. Komaki
Affiliation: Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX


The radioprotective property of thiol-containing compounds has been well known for some time. Amifostine(WR-2721) is the most well known of these agents. The proposed mechanism of action is the scavenging of radiation-induced free radicals.

A prospective randomized study was conducted to determine whether amifostine reduces the rate of severe esophagitis, hematologic, and pulmonary toxicities associated with concurrent chemoradiation and/or improves the survival of patients with inoperable NSCLC.

Materials and Methods

  • 62 patients with inoperable stage II or III NSCLC were entered onto this single institution randomized study.
  • They were treated by thoracic radiation therapy (TRT) with 1.2 Gy/Fx, bid to a total dose of 69.6 Gy and oral VP-16 and cisplatin
  • Amifostine (500 mg i.v. twice weekly) was given before chemoradiation (Arm 1); the control group received chemoradiation without amifostine (Arm 2).


  • Thirty-one patients were enrolled in each arm with a median follow-up of 6 months.
  • Patient and tumor characteristics were equally distributed in both groups.
  • Complete response (CR) occurred in 11 of the 31 patients who received amifostine (35%) and in 6 of the 31 patients (19%) who did not (p= 0.15).
  • Median survival time has not yet been reached on arm 1; it was 20 months on arm 2.
  • Severe acute esophagitis ( grade 3) was 6.5% in Arm 1 compared to 26%in Arm 2 (p=0.038).
  • Acute pneumonitis ( grade 3) was 3.2% in Arm 1 compared to 19% in Arm 2 (p = 0.045).
  • There was no significant difference in hematologic toxicities between the two arms. Hypotension (20 mm Hg decrease from baseline BP) was significantly more frequent in Arm 1 65% vs 3.0% in Arm 2 (p=0.00001).
  • Only one patient discontinued the treatment because of a hypotensive episode.

Author's Conclusions

  • Amifostine significantly reduced acute pneumonitis and severe acute esophagitis although it caused significantly more hypotensive episodes.
  • Further follow-up is needed to evaluate the long-term effects in late reacting normal tissues as well as survival.

Clinical/Scientific Implications

  • One of major implications of this study is that more rigorous cancer regimens, such as those utilizing chemoirradiation, might be employed if the integrity of normal tissue could be preserved.
  • Of course, when discussing radioprotectants, one must always be aware of the theoretical concern of tumor protection.
  • Another interesting area of active research is the use of subcutaneous amifostine, which offers a more convenient method of delivery than the i.v. form, and may have a better side-effect profile.