PURPOSE:The Radiation Therapy Oncolology Group (RTOG) 0116 trial was designed to test the ability of Amifostine to reduce the toxicity of combined chemotherapy with extended-field radiotherapy and brachytherapy (Part 2), after first determining the toxicity rate for the regimen without Amifostine (Part 1). This manuscript reports the results of Part 1. METHODS AND MATERIALS:Eligibility included patients with cervical carcinoma and high common iliac or para-aortic metastasis. Patients received extended-field radiotherapy to 45 Gy (1.8 Gy/fraction) with intracavitary irradiation. The final point A dose was 85 Gy LDR equivalent. Use of HDR was allowed. The positive para-aortic and high common iliac nodes were boosted to 54 to 59.4 Gy. Cisplatin (40 mg/m(2)) was delivered weekly during external beam and once with brachytherapy. The primary endpoint of Part 1 was acute Grade 3/4 toxicity, excluding Grade 3 leukopenia. RESULTS:A total of 26 eligible patients were entered between August 1, 2000, and December 3, 2003. Of these, 21 had para-aortic metastasis (15 also had high common iliac involvement), and 5 had high common iliac involvement only. The median follow-up was 17.1 months (range, 1.8-38.6 months) for all patients and 21.7 months (range, 11.4-38.6 months) for alive patients. The acute Grade 3/4 toxicity rate, excluding Grade 3 leukopenia was 81%. Late Grade 3/4 toxicity was 40%. Eight patients underwent surgery for complications. Sixteen (62%) patients had a complete response for both local and nodal disease. The complete local response was 92%, the complete overall nodal response rate was 62% and the regional and para-aortic nodal response rates were 60% and 71% respectively. Estimated disease-free and overall survival at 18 months are 46% and 60%. CONCLUSIONS:Extended field and intracavitary irradiation with cisplatin for para-aortic or high common iliac metastasis from cervical cancer is associated with significant acute and late toxicity.