Abstract
Epithelial growth factor receptor over-expression correlates with poor outcomes in cervical cancer. This study assessed the safety of chemoradiation with cetuximab in the treatment of women with newly diagnosed locally advanced cervical cancer.
Patients received weekly cisplatin 30 and 40mg/m2 [dose level (DL) 1 and 2] and cetuximab 400mg/m2 loading dose and then 250mg/m2 for a total of six weeks with radiotherapy (RT). Patients with nodal metastases received extended field radiation therapy (EFRT). At the maximum tolerated dose, feasibility was evaluated in a 20 patient two-stage, sequential design.
In patients receiving pelvic RT, seven were treated at DL 1 with one dose-limiting toxicity (DLT) (febrile neutropenia with grade 3 diarrhea) and three at DL 2 with two DLTs (grade 3 rash and delay in RT >8weeks). The feasibility phase was opened at DL1. Of the 21 patients treated there was one DLT (grade 4 CVA). Median RT duration was 50days (range, 42–70). In patients receiving EFRT, nine were treated at DL 1 with 1 DLT (grade 3 mucositis) and 24 in the feasibility phase with eight DLTs [delay in RT >8weeks due to toxicity (2) and one each with grade 3 or 4 small bowel obstruction, embolism, mucositis, mucositis with hypokalemia, pain with headache, and platelets with mucositis and headache]. Median EFRT duration was 56days (range, 36–74).
For patients receiving pelvic RT, cisplatin and cetuximab were feasible. For patients receiving EFRT, combination of cisplatin and cetuximab was not feasible.
► Epithelial Growth Factor Receptor (EGFR) is overexpressed in 50–70% of cervical cancers making it a rationale therapeutic target. ► When added to weekly cisplatin and whole pelvic radiation, the EGFR monoclonal antibody, cetuximab was feasible. ► When combined with cisplatin and extended field radiation, cetuximab resulted in excessive metabolic and gastrointestinal toxicity and was not feasible.