Nimotuzumab combined with radiotherapy for esophageal cancer: preliminary study of a Phase II clinical trial

Jun Liang,¹ Mingyan E,² Gang Wu,³ Lujun Zhao,⁴ Xia Li,⁵ Xia Xiu,⁶ Ning Li,¹ Bo Chen,¹ Zhouguang Hui,¹ Jima Lv,¹ Hui Fang,¹ Yu Tang,¹ Nan Bi,¹ Wenqing Wang,¹ Yirui Zhai,¹ Tao Li,¹ Dongfu Chen,¹ Shuangmei Zou,⁷ Ning Lu,⁷ Rolando Perez-Rodríguez,⁸ Junqi Zheng,⁹ Luhua Wang<sup>1

1</sup>Department of Radiotherapy, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China; ²Department of Radiotherapy, Cancer Hospital of Harbin Medical University, Harbin, People's Republic of China; ³Department of Radiotherapy, Tongji Cancer Center Hospital, Wuhan, People's Republic of China; ⁴Department of Radiotherapy, Cancer Hospital of Tianjin Medical University, Tianjin, People's Republic of China; ⁵Department of Radiotherapy, LiaoNing Province Cancer Hospital, Shenyang, People's Republic of China; ⁶Department of Radiotherapy, Beijing Hospital, Beijing, People's Republic of China; ⁷Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China; ⁸Center of Molecular Immunology, Havana, Cuba; ⁹School of Medicine, Tongji University, Shanghai, People's Republic of China

Objective: To determine the safety and therapeutic effects of nimotuzumab (h-R3) combined with radiotherapy in esophageal cancer.
Methods: This Phase II clinical trial involved 42 patients with stage II (inoperable or refused surgery) to stage IV (supraclavicular lymph node metastasis only) esophageal cancers treated between November 2008 and July 2010. All patients had squamous cell carcinomas, and all received three-dimensional conformal radiotherapy and 200 mg nimotuzumab per week during radiotherapy.
Results: There were 9, 25, and 8 patients with stage II, III and IV disease, respectively. All except two patients received 50–70 Gy radiation; 37 patients (88.1%) received more than five nimotuzumab doses. Grade III toxicities (21.4% of all adverse events) included esophagitis and gastrointestinal, dermatological and hematological toxicities. Complete response, partial response, stable disease, and progressive disease were observed in 0, 22 (52.4%), 17 (40.5%) and 3 (7.1%) patients at 1 month after the treatment. The epidermal growth factor receptor (EGFR) overexpression rate was 95.2%. After a median follow-up of 37 months, the median survival time (MST) was 14 months. The 2 year and 3 year overall survival (OS) rates were 33.3% and 26.2%, respectively. The median progression-free survival (PFS) time was 10 months. The 2 year and 3 year PFS rates were 24.5% and 22.1%, respectively. The MST in the 13 patients with (+++) EGFR expression (group A) and 7 patients with (++) EGFR expression (group B) was 15 and 11 months, respectively. The 2 year and 3 year OS rates were 46.2% and 38.5% in group A and 28.6% and 28.6% in group B, respectively (P = 0.405).
Conclusion: Although concurrent chemoradiotherapy was the standard care for locally advanced esophageal cancer, radiotherapy was the choice for those who were refused or could not tolerate chemoradiotherapy. Our study shows that nimotuzumab combined with radiotherapy was well tolerated in patients with esophageal cancer. EGFR overexpression was more common than previously reported. OS was higher after combined therapy than after historical control radiotherapy alone. Further studies are required to confirm the therapeutic efficacy of nimotuzumab in esophageal cancer.

Keywords: esophageal neoplasms, nimotuzumab, radiotherapy, targeted therapy, treatment outcomes