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Randomized Trial of Amifostine in Locally Advanced Non–Small-Cell Lung Cancer Patients Receiving Chemotherapy and Hyperfractionated Radiation: Radiation Therapy Oncology Group Trial 98-01

From the Henry Ford Health System, Detroit, MI; Radiation Therapy Oncology Group; Fox Chase Cancer Center; Thomas Jefferson University; Hospital of the University of Pennsylvania, Philadelphia, PA; M.D. Anderson Cancer Center, Houston, TX; Medical College of Wisconsin, Milwaukee, WI; University of California Los Angeles School of Nursing, Los Angeles, CA; Washington University, St Louis, MO; and Tom Baker Cancer Center, Calgary, Alberta, Canada

Address reprint requests to Benjamin Movsas, MD, Department of Radiation Oncology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202; e-mail: bmovsas1{at}hfhs.org

PURPOSE: To test the ability of the cytoprotectant, amifostine, to reduce chemoradiotherapy-induced esophagitis and evaluate its influence on quality of life (QOL) and swallowing symptoms.

PATIENTS AND METHODS: A total of 243 patients with stage II to IIIA/B non–small-cell lung cancer received induction paclitaxel 225 mg/m² intravenously (IV) days 1 and 22 and carboplatin area under the curve (AUC) days 1 and 22, followed by concurrent weekly paclitaxel (50 mg/m² IV) and carboplatin (AUC 2), and hyperfractionated radiation therapy (69.6 Gy at 1.2 Gy bid). Patients were randomly assigned at registration to amifostine (AM) 500 mg IV four times per week or no AM during chemoradiotherapy. Beyond standard toxicity end points, physician dysphagia logs (PDLs), daily patient swallowing diaries, and QOL (EORTC QLQ-C30/LC-13) were also collected. Swallowing AUC analyses were calculated from patient diaries and PDLs.

RESULTS: A total of 120 patients were randomly assigned to receive AM, and 122, to receive no AM (one patient was ineligible); 72% received AM per protocol or with a minor deviation. AM was associated with higher rates of acute nausea (P = .03), vomiting (P = .007), cardiovascular toxicity (P = .0001), and infection or febrile neutropenia (P = .03). The rate of grade 3 esophagitis was 30% with AM versus 34% without AM (P = .9). Patient diaries demonstrated lower swallowing dysfunction AUC with amifostine (z test P = .025). QOL was not significantly different between the two arms, except for pain, which showed more clinically meaningful improvement and less deterioration at 6 weeks follow-up (v pretreatment) in the AM arm (P = .003). The median survival rates for both arms were comparable (AM, 17.3 v no AM, 17.9 months; P = .87).

CONCLUSION: AM did not significantly reduce esophagitis grade 3 in patients receiving hyperfractionated radiation and chemotherapy. However, patient self-assessments suggested a possible advantage to AM that is being explored with modified dosing route strategies.

Supported by RTOG U10CA21661, CCOP U10CA37422, and Stat U10CA32115 grants from the National Cancer Institute and by Medimmune Oncology.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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