G. Zhu

Cetuximab in combination with chemoradiotherapy in Chinese patients with non-resectable, locally advanced esophageal squamous cell carcinoma: A prospective, multicenter phase II trail

BACKGROUND AND PURPOSE This multicenter phase II trial investigated cetuximab combined with chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS Eligible patients with non-resectable, locally-advanced ESCC received cetuximab 400mg/m(2) loading dose on day 1; and on day 1 of the 2nd-7th weeks: cetuximab 250mg/m(2), paclitaxel 45mg/m(2), and cisplatin 20mg/m(2), concurrent with 59.4Gy/33 fractions of radiation therapy. Primary endpoint was clinical response rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and KRAS status. RESULTS Of 55 patients enrolled, 45 completed therapy. Forty-four patients had a clinical response: 29 complete response and 15 partial response. One-year PFS and OS of 45 evaluable patients were 84.23% and 93.33%, respectively, and 2-year PFS and OS were 74.87% and 80.00%, respectively. Non-hematologic adverse events were generally grade 1 or 2; primarily rash (92.7%), mucositis (45.5%), fatigue (41.8%), and nausea (38.2%). Grade 3 hematologic adverse events included neutropenia (32.7%) and anemia (1.8%). No KRAS mutations were identified in 50 evaluated samples. CONCLUSIONS Cetuximab can be safely administered with chemoradiotherapy to patients with locally-advanced ESCC and may improve clinical response rate.

KRAS mutation status and toxicity of cetuximab, paclitaxel, cisplatin, and concurrent radiation in Chinese patients with locally advanced esophageal squamous cell carcinoma: An open-label, multicenter, phase II study.

e14650 Background: The most common type of esophageal or gastroesophageal-junction cancer in Western countries is adenocarcinoma; however, in China more than 90% of esophageal malignancies are of squamous cell carcinoma (SCC). Thus data are lacking on the potential benefits from the use of cetuximab for Chinese patients with esophageal SCC. We conducted this Chinese multicenter trial to determine the toxicity of the addition of cetuximab with paclitaxel, cisplatin, and concurrent radiation for patients with esophageal SCC and to determine whether KRAS status predicts response. METHODS Patients with unresectable locally advanced cervical, upper or mid-esophageal SCC without distant metastasis were eligible for this open-label phase II trial. All patients received cetuximab (400 mg/m2 day 1 before chemoradiotherapy and 250 mg/m2 q1w × 7 weeks), paclitaxel (45 mg/m2 q1w × 7 weeks) and cisplatin (20 mg/m2 q1w × 7 weeks) with 59.4 Gy of radiation. KRAS mutation status was assessed in tumor specimen at a centralized facility. RESULTS Fifty-five patients were enrolled and evaluable for to toxicity. Non-hematological adverse events were generally grade 1 or 2, and were most often rash (94.5%), mucositis (58.2%), fatigue (45.5%), nausea (41.8%) and hepatic dyfunction (40%). Hematologic adverse events included grade 3 neutropenia (32.7%) and grade 3 anemia (1.82%). Ten patients did not complete the protocol therapy and were not assessable for response (6 for chemotherapy dose delays, 1 for paciltaxel hypersensitivity, 1 by the treating physicians for unstated reasons, 1 for concurrent unrelated infection, and 1 for tracheo-esophageal fistula). Forty-four of the 45 evaluable patients (97.7%) had a clinical response after chemoradiation. No mutations were detected at KRAS codons 12 or 13 in the 52 available specimens. CONCLUSIONS Cetuximab can be safely administered with chemoradiation for Chinese patients with esophageal cancer and may improve the clinical response rate. KRAS mutations were too rare to be analyzed as a predictor of response.