International Journal of Radiation Oncology*Biology*Physics
Clinical investigationCervixExtended-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 1 of RTOG 0116
Introduction
Worldwide, carcinoma of the cervix is the second most common cancer in women, with an estimated 493,000 new cases and 274,000 deaths in 2002 (1). In the United States cervical cancer is decreasing in prevalence, but still accounted for more than 9,700 new cases and 3,700 deaths in 2006 alone (2). The traditional treatment for locally advanced cervical cancer is definitive radiotherapy. In 1999 the National Cancer Institute issued a clinical announcement urging strong consideration be given to delivering combined modality therapy for pelvic confined advanced cervical cancer (3). This was based on data from five randomized trials noting a 30% to 50% reduction in recurrence resulting in a survival benefit for the use of combined therapy (4, 5, 6, 7, 8).
Cervical cancer patients with para-aortic metastasis are curable with extended-field radiotherapy (9, 10, 11, 12, 13). Given the results of combined therapy in pelvic confined disease it seems logical to pursue this treatment in patients with para-aortic disease. Published reports do suggest improved outcome with the use of combined therapy although at the expense of increased toxicity (14, 15, 16, 17). Amifostine is a thiol-containing compound that has been noted to protect against radiotherapy toxicity without compromising tumor control (18). This study examined the use of Amifostine in patients with high-common iliac or para-aortic metastasis from cervical cancer treated with extended-field radiotherapy and concurrent chemotherapy. The study was designed in two parts. Part 1 delivered combined therapy without Amifostine to determine rates of toxicity. The final results of Part 1 of the trial are presented in this report.
Section snippets
Methods and Materials
Eligibility included patients with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosqumaous carcinoma of the cervix with evidence for positive para-aortic or high common iliac lymph nodes. Patients were required to have no other evidence for metastatic disease outside the pelvis (other than to the para-aortic lymph nodes), have a Zubrod performance status of 0 to 1 and no specific medical contraindication to the administration of full-dose chemotherapy. Adequate bone marrow,
Results
A total of 27 patients were entered into the study from August 1, 2001 to December 3, 2003. Of the 27 patients that were entered into Arm 1, 1 patient was ineligible because of an endometrial tumor origin, therefore this analysis reports on the remaining 26 patients. The analysis was performed on all data received and data entered at RTOG headquarters as of August 11, 2005. The median follow-up was 17.1 months (1.8–38.6 months), for all patients and 21.7 (11.4–38.6 months) for alive patients.
Discussion
This trial was designed in two parts, with the first part delivering extended-field radiotherapy with concurrent cisplatin and brachytherapy to determine toxicity rates. The second part of the trial delivers the same radiotherapy but adds concurrent Amifostine. This approach was chosen because there were insufficient data in the literature using concurrent weekly cisplatin and extended-field radiotherapy to predict the historical toxicity rates and to provide a basis of comparison for
Conclusions
The use of extended-field radiotherapy and chemotherapy as used on this trial was associated with high rates of acute and long-term toxicity and significant rates of nodal failures. It is hoped that the addition of Amifostine in Part 2 of the trial can improve toxicity rates. The Amifostine portion of the study is currently open to accrual and requires 18 patients. In addition to Amifostine, future directions could include using IMRT both to reduce toxicity and possibly improve outcome with
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Supported by RTOG U10 CA21661, CCOP U10 CA37422, and Stat U10 CA32115 grants from the National Cancer Institute (NCI). This contents of this article are the sole responsibility of the authors and do not necessarily represent the official views of the NCI.
Conflict of interest: Dr. Small is on the Speakers Bureau for Medimmune and receives research funding from Genetech.