Muto M G, Finkler N J, Kassis A I, Howes A E, Anderson L L, Lau C C, Zurawski V R, Weadock K, Tumeh S S, Lavin P
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Gynecol Oncol. 1992 Jun;45(3):265-72. doi: 10.1016/0090-8258(92)90302-y.
Refractory epithelial ovarian cancer is generally confined to the peritoneal cavity and is thus amenable to intraperitoneal (ip) therapy. Radiolabeled monoclonal antibodies raised to tumor-associated antigens offer the promise of selective tumor irradiation while reducing toxicity to normal tissues. We have conducted a phase I therapeutic trial to examine the feasibility of ip radioimmunotherapy utilizing escalating doses of 131I-labeled OC125 F(ab')2. Twenty-nine patients were each treated with a single dose of radiolabeled antibody. Twenty-eight patients were evaluable for dose-related toxicity. The toxicities most frequently observed were hematologic and gastrointestinal. Hematologic toxicity was noted in 5/14 (36%) patients receiving 18-87 mCi and in 12/14 (71%) receiving 100-144 mCi (P = 0.018). The median white blood cell nadir of 2-3K/microliters (range, 1.4-3.5K/microliters occurred at a median of 4.5 weeks and the median platelet nadir of 41K/microliters (range, 20-78K/microliters) at a median of 6.5 weeks. Mild gastrointestinal toxicity was observed in 4/14 patients (28%) at doses less than 100 mCi whereas at doses greater than or equal to 100 mCi, 11/14 (79%) patients developed nausea, vomiting, or chronic ileus (P = 0.021). This toxicity occurred most frequently in patients with protracted urinary 131I excretion. We conclude that 131I-labeled OC125 can be safely administered ip. Hematologic and gastrointestinal toxicity is predictable and related to the dose and rate of clearance of isotope.
难治性上皮性卵巢癌通常局限于腹腔，因此适合进行腹腔内（ip）治疗。针对肿瘤相关抗原产生的放射性标记单克隆抗体有望实现选择性肿瘤照射，同时降低对正常组织的毒性。我们进行了一项I期治疗试验，以研究使用递增剂量的131I标记的OC125 F(ab')2进行腹腔内放射免疫治疗的可行性。29名患者均接受了单剂量的放射性标记抗体治疗。28名患者可评估剂量相关毒性。最常观察到的毒性是血液学和胃肠道毒性。在接受18 - 87毫居里的14名患者中有5名（36%）出现血液学毒性，在接受100 - 144毫居里的14名患者中有12名（71%）出现血液学毒性（P = 0.018）。白细胞最低点中位数为2 - 3K/微升（范围为1.4 - 3.5K/微升），出现在中位时间4.5周，血小板最低点中位数为41K/微升（范围为20 - 78K/微升），出现在中位时间6.5周。在剂量小于100毫居里时，14名患者中有4名（28%）出现轻度胃肠道毒性，而在剂量大于或等于100毫居里时，14名患者中有11名（79%）出现恶心、呕吐或慢性肠梗阻（P = 0.021）。这种毒性在131I排泄时间延长的患者中最常出现。我们得出结论，131I标记的OC125可以安全地腹腔内给药。血液学和胃肠道毒性是可预测的，并且与同位素的剂量和清除率有关。
