# Neoadjuvant radiotherapy combined with fluorouracil-cisplatin plus cetuximab in operable, locally advanced esophageal carcinoma: Results of a phase I-II trial (FFCD-0505/PRODIGE-3)

## TL;DR

A clinical trial tested adding cetuximab to standard treatment for advanced esophageal cancer but found it was too toxic and did not significantly improve outcomes.

## Contribution

This study determined the optimal doses of a chemotherapy regimen combined with cetuximab for esophageal cancer and evaluated its effectiveness and toxicity.

## Key findings

- The regimen failed to achieve a pathologic complete response rate greater than 20%.
- The treatment was found to be toxic, which may have reduced chemotherapy dose-intensity.
- Median progression-free survival was 13.7 months with no median overall survival reached.

## Abstract

•Adding Cetuximab to chemoradiotherapy in advanced esophageal cancer could improve pCR.•With a 5 weeks radiotherapy, we determined the optimal doses for 5FU, Cisplatin, Cetuximab based chemotherapy.•This regimen failed to reach a pCR > 20 %, and showed to be toxic.

Adding Cetuximab to chemoradiotherapy in advanced esophageal cancer could improve pCR.

With a 5 weeks radiotherapy, we determined the optimal doses for 5FU, Cisplatin, Cetuximab based chemotherapy.

This regimen failed to reach a pCR > 20 %, and showed to be toxic.

Radiotherapy combined with fluorouracil (5FU) and cisplatin for locally advanced esophageal cancer is associated with a 20–25% pathologic complete response (pCR) rate. Cetuximab increases the efficacy of radiotherapy in patients with head and neck carcinomas. The aim of this phase I/II trial was to determine the optimal doses and the pCR rate with chemoradiotherapy (C-RT) plus cetuximab.

A 45-Gy radiotherapy regimen was delivered over 5 weeks. The phase I study determined the dose-limiting toxicity and the maximum tolerated dose of 5FU-cisplatin plus cetuximab. The phase II trial aimed to exhibit a pCR rate > 20 % (25 % expected), requiring 33 patients (6 from phase I part plus 27 in phase II part). pCR was defined as ypT0Nx.

The phase I study established the following recommended doses: weekly cetuximab (400 mg/m2 one week before, and 250 mg/m2 during radiotherapy); 5FU (500 mg/m2/day, d1-d4) plus cisplatin (40 mg/m2, d1) during week 1 and 5. In the phase II part, 32 patients received C-RT before surgery, 31 patients underwent surgery, and resection was achieved in 27 patients. A pCR was achieved in five patients (18.5 %) out of 27. After a median follow-up of 19 months, the median progression-free survival was 13.7 months, and the median overall survival was not reached.

Adding cetuximab to preoperative C-RT was toxic and did not achieve a pCR > 20 % as required. The recommended doses, determined during the phase I part, could explain these disappointing results due to a reduction in chemotherapy dose-intensity.

This trial was registered with EudraCT number 2006-004770-27.