Moore D H, Valea F, Walton L A, Soper J, Clarke-Pearson D, Fowler W C
Department of Obstetrics and Gynecology, Indiana University Medical Center, Indianapolis 46202-5274, USA.
Gynecol Oncol. 1995 Nov;59(2):267-72. doi: 10.1006/gyno.1995.0020.
Previous clinical investigations using interferons (IFNs) have shown activity against epithelial ovarian cancer. The objective of this study was to determine the maximum tolerated dose of intraperitoneal (ip) IFN-alpha 2b which could be administered in combination with intravenous (iv) cis-platinum plus cyclophosphamide chemotherapy. After comprehensive surgical staging and maximal cytoreduction, previously untreated patients with primary ovarian adenocarcinoma were entered at one of five IFN dose levels. IFN-alpha 2b (5-30 x 10(6) units) was administered ip on Day 1 (+/- Day 8). cis-Platinum (75 mg/m2) plus cyclophosphamide (750 mg/m2) were administered iv on Day 2 with prophylactic hydration and anti-emetics. Courses were repeated every 3 weeks for 8 cycles. Adverse effects were recorded using standard Gynecologic Oncology Group toxicity scales. Fifteen patients with mean age 56 years (range 43-73) were entered and received a combined total of 100 treatment cycles. Catheter-related complications occurred in 8 patients, and in three cases lead to catheter removal and discontinuation of ip therapy. Two patients experienced grade 2-3 nephrotoxicity and 1 experienced grade 2 peripheral neuropathy. There was a single episode of chemical peritonitis. Myelosuppression was the dose-limiting toxicity with grade 3-4 leukopenia complicating 6, 5, 12, 11, and 17 cycles at dose levels 1-5, respectively. No patient completed planned treatment without interruption or dose reduction. Planned cis-platinum dose intensity was most compromised at the fifth IFN-alpha 2b dose level. The maximum tolerated dose of IFN-alpha 2b was determined to be 20 x 10(6) units repeated on Days 1 and 8 of this 21-day cis-platinum plus cyclophosphamide chemotherapy cycle.
以往使用干扰素（IFN）的临床研究显示其对上皮性卵巢癌具有活性。本研究的目的是确定腹腔内（ip）注射α-2b干扰素与静脉内（iv）顺铂加环磷酰胺化疗联合应用时的最大耐受剂量。在进行全面的手术分期和最大程度的肿瘤细胞减灭术后，将先前未接受过治疗的原发性卵巢腺癌患者纳入五个IFN剂量水平之一。在第1天（±第8天）腹腔内注射α-2b干扰素（5 - 30×10⁶单位）。在第2天静脉注射顺铂（75 mg/m²）加环磷酰胺（750 mg/m²），同时进行预防性水化和使用止吐药。每3周重复一个疗程，共进行8个周期。使用标准的妇科肿瘤学组毒性量表记录不良反应。15名平均年龄56岁（范围43 - 73岁）的患者被纳入并共接受了100个治疗周期。8名患者出现与导管相关的并发症，其中3例导致导管拔除和腹腔内治疗中断。2名患者出现2 - 3级肾毒性，1名患者出现2级周围神经病变。发生了1次化学性腹膜炎。骨髓抑制是剂量限制性毒性，在剂量水平1 - 5时，分别有6、5、12、11和17个周期出现3 - 4级白细胞减少。没有患者在不中断或不减量的情况下完成计划的治疗。在第五个α-2b干扰素剂量水平时，计划的顺铂剂量强度受到的影响最大。确定α-2b干扰素的最大耐受剂量为20×10⁶单位，在这个21天的顺铂加环磷酰胺化疗周期的第1天和第8天重复给药。
