A phase I trial of tailored radiation therapy with concomitant cetuximab and cisplatin in the treatment of patients with cervical cancer: A gynecologic oncology group study

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Oklahoma, Oklahoma City, OK 73190, USA. Electronic address: .
Gynecologic Oncology (Impact Factor: 3.77). 09/2012; 127(3). DOI: 10.1016/j.ygyno.2012.08.030
Source: PubMed


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 40 mg/m(2) [dose level (DL) 1 and 2] and cetuximab 400mg/m(2) loading dose and then 250 mg/m(2) 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 >8 weeks). The feasibility phase was opened at DL1. Of the 21 patients treated there was one DLT (grade 4 CVA). Median RT duration was 50 days (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 >8 weeks 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 56 days (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.

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Available from: David Scott Miller, Sep 30, 2015
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    • "EGFR-targeting agents were the first molecules to be tested as radiotherapy partners in this setting, with the EGFR tyrosine kinase inhibitor erlotinib demonstrating feasibility and safety in concomitant administration with radiotherapy at the dose of 150 mg daily in a pilot phase I trial [44]. The chimeric monoclonal antibody against EGFR cetuximab was also tested in combination with radiotherapy in patients with newly diagnosed locally advanced cervical cancer in a recently reported phase I trial showing that the combination was feasible for patients receiving pelvic radiotherapy but not feasible for patients receiving extended field radion therapy due to nodal metastases [45]. Based on this preliminary evidence, a phase II pilot trial incorporating cetuximab, cisplatin, and irradiation in women with locally advanced cervical cancer is currently ongoing ( "
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