Clinical Investigation
Cetuximab With Concurrent Chemoradiation for Esophagogastric Cancer: Assessment of Toxicity

https://doi.org/10.1016/j.ijrobp.2007.07.2325Get rights and content

Purpose

To determine the feasibility and toxicity of the addition of cetuximab with paclitaxel, carboplatin, and radiation for patients with esophagogastric cancer on a Phase II study.

Methods and Materials

Patients with locoregional esophageal and proximal gastric cancer without distant organ metastases were eligible. All patients received cetuximab, paclitaxel, and carboplatin weekly for 6 weeks with 50.4 Gy radiation.

Results

Sixty patients were enrolled, 57 with esophageal cancer and 3 with gastric cancer. Forty-eight had adenocarcinoma and 12 had squamous cell cancer. Fourteen of 60 patients (23%) had Grade 3 dermatologic toxicity consisting of a painful, pruritic acneiform rash on the face outside of the radiation field. The rates of Grades 3 and 4 esophagitis were 12% and 3%, respectively. Three patients had Grade 3/4 cetuximab hypersensitivity reactions and were not assessable for response. Forty of 57 patients (70%) had a complete clinical response after chemoradiation.

Conclusion

Cetuximab can be safely administered with chemoradiation for esophageal cancer. Dermatologic toxicity and hypersensitivity reactions were associated with the addition of cetuximab. There was no increase in esophagitis or other radiation-enhanced toxicity.

Introduction

The Radiation Therapy Oncology Group protocol 8,501 demonstrated that concurrent cisplatin, fluorouracil (5-FU), and radiation improved survival compared with radiation alone for patients with esophageal cancer (1). To attempt to further improve outcome, multiple combinations of paclitaxel, cisplatin, carboplatin, irinotecan, 5-FU, and concurrent radiation have been evaluated for patients with esophageal cancer 2, 3, 4. Unfortunately, none of these newer regimens has achieved a clear benefit 2, 3, 4.

Therapies that block aberrant growth factor signal transduction pathways have substantial promise in human malignancies, including esophageal cancer. The epidermal growth factor receptor (EGFR) is a tyrosine kinase cell surface receptor encoded by the c-erbB-1 protooncogene (5). The EGFR signal transduction network plays an important role in cancer growth and progression as well as protection from apoptosis (6). EGFR is expressed in 50–80% of all esophageal cancers 7, 8, 9, 10.

Cetuximab, an immunoglobulin-G1 chimerized, monoclonal antibody, binds specifically to EGFR (11). Preclinical models have suggested synergy between cetuximab, paclitaxel, cisplatin, and radiation 12, 13. For patients with locally advanced head and neck cancer, the combination of cetuximab and radiation demonstrated a survival benefit (14). However, the safety of cetuximab in combination with concurrent chemotherapy and radiation has not been established and the initial report suggested substantial toxicity (15). A Phase II study of cetuximab, paclitaxel, carboplatin, and concurrent radiation was therefore initiated. The primary endpoint was to establish the safety of this regimen. Carboplatin was used instead of cisplatin to attempt to distinguish whether nonhematologic toxicities were due to chemoradiation or the addition of cetuximab.

Section snippets

Patient eligibility

Eligible patients included those with pathologically documented adenocarcinoma or squamous cell cancer of the esophagus or adenocarcinoma of the proximal stomach with T2-T4 or nodal disease. Patients with gastric extension and adenopathy that included mediastinal, supraclavicular, celiac, and portal disease were eligible. Patients with ascites, metastatic disease to other organs, and peritoneal implants were ineligible. Surgical resection was not a required component of this study; therefore,

Patient characteristics

Between December 2004 and October 2006, 60 patients were enrolled in this study. Table 1 shows selected demographics and disease characteristics. The median age was 60 (range, 30–87) years. Fifty-seven had esophageal cancer and 3 had proximal gastric cancer. Forty-eight patients had adenocarcinoma and 12 had squamous cell cancer. Two patients had cervical esophageal cancer. Of the 48 patients with adenocarcinoma, 18 had either celiac lymphadenopathy >2 cm or gastrohepatic or supraclavicular

Discussion

This Phase II study demonstrated that cetuximab can be safely administered with paclitaxel, carboplatin, and radiation for patients with esophagogastric cancer. Cutaneous toxicities and hypersensitivity reactions were increased with the addition of cetuximab. The rates of Grades 2, 3, and 4 dermatologic toxicity were 40%, 25% and 0%, respectively. The most significant dermatologic toxicity consisted of a painful, pruritic acneiform rash on the face. Other common but less severe areas of

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    Presented in part at the 48th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), November 5–9, 2006, Philadelphia, PA.

    Dr. Safran and Dr. Mohan report receiving grant support and honoraria from Bristol-Myers in the amount of less than $100,000. No other potential conflict of interest relevant to this article was reported.

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