Amifostine As Mucosal Protectant in Patients with Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Receiving Intensive Chemotherapy and Thoracic Radiotherapy (RT): Results of the Radiation Therapy Oncology Group (RTOG) 98-01 Study

Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 22, 2003

Presenter: Maria Werner-Wasik, MD
Presenter's Affiliation: Thomas Jefferson University
Type of Session: Scientific


    20-50% of patients receiving thoracic RT with concurrent chemotherapy experience severe esophagitis. Amifostine (AMI) is a radioprotectant that has been shown to improve esophagitis both in animal models and in early clinical trials. The current study examines the effectiveness of AMI at reducing severe esophagitis in patients undergoing concurrent chemotherapy and radiation for NSCLC.

Materials and Methods

  • Good prognosis patients (<5% weight loss, KPS>70) with inoperable stage II or unresectable stage IIIA/B NSCLC were eligible for treatment.
  • All patients were treated with 2 cycles of induction chemotherapy consisting of paclitaxel (225mg/m2) and carboplatin (AUC=6) every 3 weeks followed by concurrent chemotherapy (paclitaxel (50mg/m2) and carboplatin (AUC=2)) and hyperfractionated RT (69.6 Gy/1.2Gy bid).
  • Patients were randomized to receive AMI (500 mg IV Mon-Thurs) or no AMI.
  • Patients received AMI 15-60 min before RT on RT only treatment days, and 90-180 min before RT on days where they were receiving both chemotherapy and RT.
  • All but 15 patients received their AMI prior to their afternoon fraction of RT, while the remaining 15 received it prior to their morning fraction.


  • 243 patients were entered into the study.
  • The study groups were well-balanced with regards to age, gender, performance status, histology, and stage.
  • Patients were generally able to receive their assigned treatment with 91% and 99% receiving their chemotherapy on the AMI and NO AMI arms, respectively, 80% and 85% receiving their assigned RT, and 72% receving their AMI.
  • For all acute toxicities, there was no difference between the two groups. 74 patients in the AMI arm experience grade 3 or higher acute toxicity compared to 70 patients in the NO AMI arm.
  • There was no difference in all late toxicities: 11 patients in the AMI arm experience grade 3 or higher late toxicity compared to 15 in the NO AMI arm.
  • Survival was similar between the two groups with median survival time of 15.8 mo in the AMI arm vs. 15.6 mo in the NO AMI arm; 2-year OS was 31% in the AMI arm vs. 29% in the NO AMI arm.
  • For esophagitis, patients were scored by physician assessment in the clinic and by patient swallowing diary. An area under to curve was generated by plotting the patient or physician score on a graph over time and obtaining an overall esophagitis score.
  • There was no difference in the two arms with regards to physician score (AUC 1.06 for AMI vs. 1.1 for NO AMI, p=0.32).
  • There was a difference for patient-reported swallowing (AUC 2.19 for AMI vs. 2.34 for NO AMI, p=0.025) for patients with at least 15 entries recorded in their swallowing diary.
  • There was no difference in late esophagitis (p=0.6) or for all quality-of-life measures.

Author's Conclusions

  • AMI failed to decrease the rates of severe esophagitis in patients receiving concurrent chemotherapy and hyperfractionated RT at these dose levels and schedules.
  • Based on the swallowing studies, there was a decrease in the AUC with the addition of AMI.
  • Given the improved patient-scored swallowing studies, there may still be a role for AMI in patients receiving thoracic RT.

Clinical/Scientific Implications

    A limiting factor in escalating radiation doses in cancer treatment is the rate of normal tissue toxicity, and the ability to decrease esophagitis in the treatment of NSCLC would not only improve patient QOL, but also allow physicians to escalate dose. The findings of this study are somewhat disappointing in the overall lack of benefit seen with the addition of AMI. AMI has been shown to be effective in decreasing the toxicity of radiation in head and neck cancer patients by reducing xerostomia, and has been shown to be effective in preclinical and early clinical studies. However, in this study, overall, there was no difference seen in rates of esophagitis between the two study arms. Nevertheless, the small rate of improvement in swallowing scores reported by the patient are somewhat encouraging. Although AMI was ineffective with this regimen of chemotherapy and RT at these doses, further studies may help determine if AMI will ultimately be beneficial in this group of patients. In this study, AMI was given 4 of 5 treatment days prior to one of the two radiation sessions each day, typically the afternoon session. Thus, radioprotection would only be expected for approximately half the overall treatments by this regimen and may not be enough to show improvement. It would be interesting to look at AMI daily with radiation with only 1 treatment per day in a future trial.

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