A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer

Abstract

Background:Preoperative chemoradiotherapy (CRT) improves the survival of patients with oesophageal cancer when compared with surgery alone.Methods:We conducted a phase II, multicenter trial of FOLFOX-4 and cetuximab in patients with locally advanced oesophageal cancer (LAEC) followed by daily radiotherapy (180 cGy fractions to 5040 cGy) with concurrent weekly cetuximab. Cytokines levels potentially related to cetuximab efficacy were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, at week 8 and at week 17. Primary end point was complete pathological response rate (pCR).Results:In all, 41 patients were enroled. Among 30 patients who underwent surgery, a pCR was observed in 8 patients corresponding to a rate of 27%. The most frequent grade 3/4 toxicity was skin (30%) and neutropenia (30%). The 36-month survival rates were 85 and 52% in patients with pathological CR or PR vs 38 and 33% in patients with SD or PD.Conclusions:Incorporating cetuximab into a preoperative regimen for LAEC is feasible; no correlation between cytokines changes and patient outcome was observed. Positron emission tomography/computed tomography study even if influenced by the small number of patients appears to be able to predict patients outcome both as early and late metabolic response.

Immuno-PET Imaging and Radioimmunotherapy of 64Cu-/177Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model

“…However, most patients are diagnosed with locally advanced tumors, regional lymph node involvement, or metastatic disease (14). Clinical trials have attempted to improve the clinical outcome by reducing the rate of local disease recurrence through integrating radiotherapy and chemotherapy in patients with ESCC, but a clear benefit has never been achieved (15,16). Thus, development of adequate screening techniques and effective novel therapeutic regimens are urgently needed.…”

Nonsurgical Management of Esophageal Cancer

“…Chemoradiation regimens using paclitaxel (Goldberg et al, 2003;Bains et al, 2002;Orditura et al, 2010;Ruppert et al, 2010), docetaxel (Pasini et al, 2005;Spigel et al, 2010), irinotecan (Ruppert et al, 2010;Ilson et al, 2002;Watkins et al, 2011;Sun et al, 2011), oxaliplatin (Spigel et al, 2010;De Vita et al, 2011;Chiarion-Sileni et al, 2009), epirubicin (Sun et al, 2011) and pemetrexed (Jatoi et al, 2010) have shown encouraging results. Biologic agents, such as cetuximab, trastuzumab, erlotinib, celecoxib and bevacizumab (De Vita et al, 2011;Safran et al, 2002;Enzinger et al, 2003;Suntharalingam et al, 2006) are being used as the foundations for new regimens which may enhance chemoradiation and target systemic micrometastases. Whether these investigational approaches offer improved results compared to conventional chemoradiation regimens based on 5-FU and cisplatin is not known.…”

Emerging Therapies for Esophageal Cancer

“…Finally, a trial centered at Brown University is evaluating the rate of complete pathologic response as determined by surgical resection or post treatment endoscopy (for patients not undergoing resection) for the treatment regimen being tested (NCT00439608). While cetuximab administered as a single agent had minimal clinical activity in patients with advanced esophageal cancers, these ongoing phase 2 clinical trials of EGFR inhibitors in combination with other agents may define a role for these agents in the treatment [37,38].…”