PhaseⅠStudy of nimotuzumab combined with postoperative chemoradiotherapy in Chinese patients with malignant glioma / 中国肿瘤临床

ABSTRACT

Objective:The poor prognosis of patients with malignant gliomas (MG) has led to the search for new therapeutic strat-egies. Recently, nimotuzumab has been studied as a new anti-EGFR-receptor humanized monoclonal antibody in patients with MG, who showed improvement of outcome and good tolerability. We conducted phase I of our study to determine the toxicity, tolerated dose, and clinical feasibility of nimotuzumab in combination with concurrent chemoradiotherapy for Chinese MG patients after surgical resection. Methods:Patients with pathologically proven grades 3 and 4 glioma were enrolled in the study. The protocol included infu-sions of nimotuzumab plus standard Stupp schedule (postoperative radiotherapy in a total dose of 60 Gy in combination with daily te-mozolomide). Patients received 6 weekly infusions of nimotuzumab at three levels (100, 200, and 400 mg/week). If none of the first three patients enrolled at a dose level experienced dose-limiting toxicity (DLT), the dose was increased, as appropriate. If DLT was ob-served, another three patients were added to the dose level. Results:Nine patients with MG were enrolled, including 7 with grade 3 MG and 2 with glioblastoma. The treatment was well tolerated, and no evidence of grade 3 or 4 adverse events was detected, even at the highest level (400 mg/week). Grade 1 or 2 myelosuppression was the most common toxicity. Three months after treatment, stable dis-ease occurred in 5 patients, whereas progression disease was observed in 4 patients. Conclusion:Nimotuzumab combined with concur-rent chemoradiotherapy was associated with mild toxicity in Chinese MG patients.