Stephenson Joe J, Gregory Charles, Burris Howard, Larson Tim, Verma Udit, Cohn Allen, Crawford Jeffrey, Cohen Roger B, Martin Julie, Lum Peggy, Yang Xinqun, Amado Rafael G
Cancer Centers of the Carolinas, Greenville, SC 29605, USA.
Clin Colorectal Cancer. 2009 Jan;8(1):29-37. doi: 10.3816/CCC.2009.n.005.
This study evaluated safety, pharmacokinetics, and efficacy of 2 dose schedules and 2 infusion times of panitumumab in patients with advanced solid malignancies.
This phase I multicenter, open-label study sequentially enrolled patients with advanced solid tumors refractory to standard therapy, or for which no standard therapy exists, to receive panitumumab 6 mg/kg every 2 weeks or 9 mg/kg every 3 weeks. Patients receiving panitumumab every 2 weeks received either all infusions over 60 minutes or a 60-minute infusion for the first dose followed by 30-minute infusions if the first infusion was well tolerated. Patients in the every-3-week cohort received 60-minute infusions. Safety outcomes included the incidence of adverse events and antipanitumumab antibody formation. Pharmacokinetic properties were determined. Efficacy endpoints included response rate and duration of response.
Eighty-six patients were enrolled; 84 (98%) received panitumumab. Treatment-related adverse events occurred in 90% of patients. Safety profiles were similar between patients receiving 30-minute (n = 20) and 60-minute (n = 43) infusions every 2 weeks and patients receiving panitumumab every 3 weeks (n = 21). Panitumumab exposure at steady state increased dose proportionally, and peak serum concentrations were similar in patients receiving either 30- or 60-minute infusions every 2 weeks. Objective responses were seen in 4 patients (5%) with colon, rectal, esophageal, and bladder cancers.
Similar drug exposures and safety profiles were observed in patients receiving panitumumab 6 mg/kg every 2 weeks with either 30- or 60-minute infusions and antitumor activity was seen in some patients. Exposure increased approximately dose proportionally at steady state.
本研究评估了帕尼单抗两种给药方案和两种输注时间在晚期实体恶性肿瘤患者中的安全性、药代动力学和疗效。
这项I期多中心、开放标签研究依次纳入对标准治疗难治或不存在标准治疗的晚期实体瘤患者，接受每2周6mg/kg或每3周9mg/kg的帕尼单抗治疗。每2周接受帕尼单抗治疗的患者，所有输注时间为60分钟，或首剂输注60分钟，若首剂输注耐受性良好，则后续输注30分钟。每3周治疗组的患者接受60分钟输注。安全性结果包括不良事件发生率和抗帕尼单抗抗体形成情况。测定药代动力学特性。疗效终点包括缓解率和缓解持续时间。
共纳入86例患者；84例（98%）接受了帕尼单抗治疗。90%的患者发生了与治疗相关的不良事件。每2周接受30分钟（n = 20）和60分钟（n = 43）输注的患者与每3周接受帕尼单抗治疗的患者（n = 21）的安全性概况相似。稳态时帕尼单抗的暴露量与剂量成比例增加，每2周接受30分钟或60分钟输注的患者的血清峰值浓度相似。4例（5%）患有结肠癌、直肠癌、食管癌和膀胱癌的患者出现了客观缓解。
每2周接受6mg/kg帕尼单抗、输注时间为30分钟或60分钟的患者中观察到相似的药物暴露和安全性概况，部分患者出现了抗肿瘤活性。稳态时暴露量随剂量大致成比例增加。
