Extended Field Irradiation and Intracavitary Brachytherapy Combined With Cisplatin Chemotherapy for Cervical Cancer With Positive Para-Aortic or High Common Iliac Lymph Nodes: Results of Arm 2 of RTOG 0116
Cervical cancer patients with para-aortic or high common iliac disease have been treated with extended field irradiation and brachytherapy with significant toxicity when combined with chemotherapy. RTOG 0116 was designed to test the ability of Amifostine, a cytoprotective agent, to reduce the acute toxicity of combined chemotherapy with extended field radiotherapy and brachytherapy.
Materials/Methods
RTOG 0116 was designed as a two-part trial. Part one delivered extended field irradiation and brachytherapy combined with weekly cisplatin chemotherapy, part two adds Amifostine. Based on the estimate of toxicity in part one, 16 evaluable patients are required to detect a 40% reduction in grade 3&4 non-hematologic toxicity (excluding grade 3 leukopenia) from 77% to 46%. Eligibility included patients with squamous, adeno or adenosquamous carcinoma of the cervix with evidence for high common iliac or para-aortic metastasis. Patients were treated with extended field radiotherapy from the T11/T12 interspace through the pelvis for a total dose of 45 Gy in 25 fractions with intracavitary irradiation. IMRT was not allowed. The final point A dose was 85 Gy LDR equivalent. HDR was allowed. The positive para-aortic and iliac nodes were to be boosted to a total dose of 54 to 59.4 Gy at the investigator's discretion. Cisplatin at a dose of 40 mg/m2 was delivered weekly during external beam and once with brachytherapy. Amifostine at 500 mg was to be delivered with every fraction of radiotherapy and brachytherapy in two divided subcutaneous injections.
Results
The study opened on 8/1/01 and closed 2/26/07 after accruing 45 patients, 18 for the second part with amifostine. This analysis reports the primary endpoint for the patients entered on the second part of the trial. Of these 18 patients 2 were ineligible, one withdrew from trial and one patient does not have toxicity data available. Seven of the remaining 14 patients (50%) were noted to have para-aortic metastasis with the remaining having high common iliac metastasis. Follow-up ranged from 0.3–22.6 months with a median of 8.9 months. Only one of the 14 patients had amifostine delivered per protocol. Eight discontinued related to patient refusal, 4 for toxicity and 1 patient did not report a reason. The median dose of amifostine delivered was 3,250 mg (500–13,500). Acute overall worst toxicity excluding grade 3 leukopenia was noted to be grade 2 in 2 patients (14%), grade 3 in 9 patients (64%) and grade 4 in 3 patients (21%). Worst non-hematologic toxicity was grade 1 in 2 patients (14%), grade 2 in 1 patient (7%), grade 3 in 10 patients (71%) and grade 4 in 1 patient (7%). One patient to date has suffered a late grade 3 kidney toxicity. Overall 12 of the 14 (85%) patients on the amifostine part of the trial experienced a grade 3 or 4 acute toxicity compared to 77% of the patients treated in part one without amifostine (p = 0.99). Efficacy and late toxicity await further follow-up.
Conclusions
Extended field and intracavitary irradiation with cisplatin chemotherapy for para-aortic or high common iliac metastasis from cervical cancer is associated with significant acute toxicity. Amifostine, as delivered in this study, did not reduce acute toxicity. Supported by NCI grants U24 CA81647, U10 CA21661, U10 CA37422.
Author Disclosure: W. Small, Medimmune, D. Speakers Bureau/Honoraria; K. Winter, None; C. Levenback, None; R. Iyer, None; S. Hymes, None; A. Jhingren, None; D. Gaffney, None; B. Erickson, None; K. Greven, None.
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