Juweid M, Swayne L C, Sharkey R M, Dunn R, Rubin A D, Herskovic T, Goldenberg D M
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA.
Gynecol Oncol. 1997 Dec;67(3):259-71. doi: 10.1006/gyno.1997.4870.
Epithelial ovarian cancer (EOC) is known to produce carcinoembryonic antigen (CEA), and the plasma CEA level is frequently elevated in patients with advanced stage and bulk of tumor. This study reports the results of a phase I therapy trial with intravenously administered 131I-MN-14 anti-CEA monoclonal antibody (MAb) in patients with EOC.
Fourteen patients with advanced refractory EOC were given escalating intravenous doses (two received 30 mCi/m2, six 40 mCi/m2, and six 50 mCi/m2) of 131I-MN-14 IgG. All patients received a diagnostic study with 8 mCi (0.6 mg) of 131I-MN-14 IgG 1 week prior to their therapy infusion. Tumor targeting was assessed by external scintigraphy, toxicity according to the Radiation Therapy Oncology Group criteria, and therapy responses by CT and serum CA-125.
The MAb scan was positive in all 14 treated patients. Myelosuppression was the only observed treatment-related toxicity. Dose-limiting toxicity, defined as grade 4 leukopenia or thrombocytopenia of any duration, or grade 3 leukopenia or thrombocytopenia of > 2 weeks, was not seen at the 30 or 40 mCi/m2 dose levels. However, 2 of 6 patients treated at 50 mCi/m2 had a grade 4 thrombocytopenia or a grade 3 thrombocytopenia lasting 18 days. Of the 14 patients, 1 with diffuse peritoneal implants of < or = 2 cm had a complete clinical remission by CT and CA-125 for 8 months, following an initial partial remission for 10 months, both at the 40 mCi/m2 dose level. Another patient had a mixed response for 1 month.
MN-14 anti-CEA MAb is a suitable agent for tumor targeting and may have a therapeutic potential in patients with chemotherapy-refractive EOC, especially those with minimal disease.
已知上皮性卵巢癌（EOC）会产生癌胚抗原（CEA），晚期及肿瘤负荷大的患者血浆CEA水平常升高。本研究报告了一项针对EOC患者静脉注射131I-MN-14抗CEA单克隆抗体（MAb）的I期治疗试验结果。
14例晚期难治性EOC患者接受递增静脉剂量（2例接受30mCi/m²，6例接受40mCi/m²，6例接受50mCi/m²）的131I-MN-14 IgG治疗。所有患者在治疗输注前1周接受8mCi（0.6mg）的131I-MN-14 IgG诊断性检查。通过外部闪烁显像评估肿瘤靶向性，根据放射治疗肿瘤学组标准评估毒性，并通过CT和血清CA-125评估治疗反应。
14例接受治疗的患者MAb扫描均为阳性。骨髓抑制是唯一观察到的与治疗相关的毒性。在30或40mCi/m²剂量水平未观察到剂量限制性毒性，定义为任何持续时间的4级白细胞减少或血小板减少，或持续>2周的3级白细胞减少或血小板减少。然而，6例接受50mCi/m²治疗的患者中有2例出现4级血小板减少或持续18天的3级血小板减少。14例患者中，1例弥漫性腹膜种植灶≤2cm的患者在40mCi/m²剂量水平，最初部分缓解10个月后，通过CT和CA-125完全临床缓解8个月。另1例患者有为期1个月的混合反应。
MN-14抗CEA MAb是一种适合肿瘤靶向的药物，对化疗难治性EOC患者，尤其是疾病轻微的患者可能具有治疗潜力。
