Clinical investigation
Cervix
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 1 of RTOG 0116

Presented at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), Denver, CO, October 16-20, 2005.
https://doi.org/10.1016/j.ijrobp.2007.01.026Get rights and content

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/m2) 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 Decemeber 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.

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.

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