Elsevier

Clinical Colorectal Cancer

Volume 18, Issue 4, December 2019, Pages 301-306
Clinical Colorectal Cancer

Original Study
A Phase II Study of Capecitabine/Oxaliplatin With Concurrent Radiotherapy in Locally Advanced Squamous Cell Carcinoma of the Anal Canal

https://doi.org/10.1016/j.clcc.2019.06.003Get rights and content

Abstract

Introduction

Squamous cell carcinoma of the anal canal (SCCA) presents a rising incidence in the United States. Standard of care for locally advanced disease is comprised of infusional 5-fluorouracil with mitomycin C or cisplatin concurrent with radiation therapy (RT). We designed this trial to evaluate the efficacy and safety of a more convenient regimen composed of capecitabine and oxaliplatin.

Patients and Methods

This was a single-arm, phase II trial, with treatment-naive stage II to IIIB (TX,1-4NxM0) SCCA patients. The regimen was composed of capecitabine (825 mg/m2 twice per day for 5 days) and oxaliplatin (50 mg/m2 weekly) during weeks 1 through 6, concurrent with RT (XELOX-XRT; group 1). After the first 11 patients, the study was amended to omit chemotherapy during the third and sixth weeks (group 2). The primary objective was 3-year time to treatment failure (TTF) and safety. Secondary objectives were complete response (CR) rate, locoregional control, colostomy-free survival (CFS), and overall survival (OS).

Results

Twenty patients were enrolled. Seven patients of group 1 (63%) developed Grade 3 toxicity, which reduced to 22% in Group 2. No Grade 4 toxicities were noted. The median RT dose was 55 Gy. CR occurred in 100% of the 19 patients evaluable for response at 12 to 14 weeks. After a median follow-up of 47.6 months, 2 patients had local recurrence and 1 had distant recurrence. Three-year TTF was 90.0%, with similar rates between groups 1 and 2 (respectively, 90.9% vs. 88.8%, P = .984). Three-year CFS was 90.0%. The median OS has not been reached.

Conclusion

The XELOX-XRT regimen is safe, with promising efficacy, and should be explored in larger trials for the treatment of locally advanced SCCA.

Introduction

Squamous cell carcinoma of the anal canal (SCCA) is a malignancy comprising only 1.5% of all gastrointestinal malignancies.1 Combined chemoradiation therapy is provided with curative intent for localized disease.2, 3, 4 However, often considered rare in incidence, the incidence continues to rise annually in the United States by 2.2% per year.5, 6 For the past 3 decades, previous pivotal trials have supported the use of 5-fluorouracil (5-FU) with mitomycin C (MMC) as a standard chemotherapy regimen with concurrent radiation therapy for curative intent.2, 3, 4, 7 5-FU with cisplatin has also been investigated as an alternative regimen for radiation sensitization.2, 3, 4 Regardless, each regimen requires intravenous administration, which can be tedious for some patients. Within the past decade, the oral fluoropyrimidine, capecitabine, has been determined to be an option for intravenous 5-FU for radiation sensitization and for systemic treatment in colorectal cancer.8, 9 In addition, the third-generation platinum agent, oxaliplatin, has also been determined to have similar properties.10, 11, 12 Therefore, to explore this concept, a phase II trial of XELOX (capecitabine with oxaliplatin) with concurrent radiation therapy (XELOX-XRT) was conducted to explore the use of this combination in locally advanced SCCA.

Section snippets

Study Design and Participants

The present study was a single-arm, phase II trial, completed at M.D. Anderson Cancer Center. Patients were required to be treatment-naive. All patients were required to be stage II to IIIB according to the American Joint Committee on Cancer (TX, 1-4 NxM0); 16 years old or older, and Eastern Cooperative Oncology Group performance status 0 to 1. Patients were required to have a baseline computed tomography (CT) scan of the chest, abdomen, and pelvis but were not required to have measurable

Results

Between the years of 2004 and 2008, a total of 20 patients were enrolled. The median age was 55 years old. Most of our population was comprised of women and patients with node-positive disease (Table 2). Because of slow patient enrollment, the study was closed prematurely. All patients were evaluated for toxicity, but only 19 patients were considered evaluable for response. Seven of the first 11 patients (group 1) enrolled with the original chemotherapy dose developed Grade 3 gastrointestinal

Discussion

As the incidence of SCCA continues to rise,5, 6 new treatment options should be pursued. Our analysis showed that XELOX-XRT is a promising regimen with significant efficacy. The treatment of locally advanced SCCA has remained largely unchanged for 3 decades, with 5-FU and MMC and concurrent radiation therapy remaining the standard of care.2, 3, 4, 7 The combination cisplatin and 5-FU with radiation has also been proven successful in treatment of this disease. However, it is essential to propose

Conclusion

To date, our study is the first prospective study to show the feasibility of oxaliplatin-based treatment in locally advanced anal cancer. Larger randomized clinical trials have established 5-FU with MMC as the treatment of choice with concurrent radiation therapy in early stage disease or 5-FU with cisplatin as the primary alternative.2, 3, 4 The XELOX regimen might be considered as a promising alternative regimen. The findings of our XELOX-XRT study support the pursuit of this chemotherapy

Disclosure

The study was designed by the investigators. The sponsor for this protocol was Sanofi-Aventis, which did not have a role in writing the article. The corresponding author had full access to all of the data and the final responsibility for the decision to submit for publication. The authors have stated that they have no conflicts of interest.

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    • This trial is registered at ClinicalTrials.gov (NCT00093379).

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