Hirabayashi K, Okada E
Department of Obstetrics and Gynecology, Fukuyama National Hospital, Japan.
Cancer. 1993 May 1;71(9):2769-75. doi: 10.1002/1097-0142(19930501)71:9<2769::aid-cncr2820710914>3.0.co;2-m.
Based on the fact that combination chemotherapy with cisplatin, ifosfamide, and bleomycin generated a 69% response rate in patients with recurrent cervical cancer; that 254-S (a cisplatin analogue) monotherapy generated a 46.3% response rate for cervical cancer, which was higher than those generated by cisplatin and carboplatin in historic comparison; and that peplomycin is a bleomycin analogue with improved pulmonary toxic effects, a combination regimen with 254-S, ifosfamide, and peplomycin was evaluated in an animal experiment and a clinical study in patients with advanced or recurrent cervical cancer with an expectation that the regimen might show a higher efficacy than 254-S monotherapy and the combination regimen including cisplatin.
In the clinical testing, 254-S was administered intravenously (IV) at 80-100 mg/m2, ifosfamide was administered IV at 1500 mg/patient for 5 days, and peplomycin was administered intramuscularly at 5 mg/patient for 6 days. This treatment was repeated every 4 weeks.
As a result, this regimen showed additive or synergistic antitumor effects in mice receiving B16 melanoma transplants. In the clinical study, 83.8% and 60.9% response rates were obtained in 37 previously untreated patients with Stage III or IV cervical cancer and 23 with recurrent cervical cancer, respectively. The dose-limiting factor was bone marrow toxic effects, which were tolerable. The other toxic effects were mild, and there were no deaths.
From these results, this combination regimen was thought worthy of evaluation in a Phase III comparative study in patients with advanced or recurrent cervical cancer.
基于顺铂、异环磷酰胺和博来霉素联合化疗对复发性宫颈癌患者产生了69%的缓解率这一事实；254-S（一种顺铂类似物）单药治疗对宫颈癌产生了46.3%的缓解率，在历史对照中高于顺铂和卡铂所产生的缓解率；以及培普利霉素是一种肺毒性有所改善的博来霉素类似物，对晚期或复发性宫颈癌患者进行了一项动物实验和临床研究，评估了254-S、异环磷酰胺和培普利霉素的联合方案，期望该方案可能显示出比254-S单药治疗和顺铂联合方案更高的疗效。
在临床试验中，254-S以80 - 100mg/m²的剂量静脉注射，异环磷酰胺以1500mg/患者的剂量静脉注射5天，培普利霉素以5mg/患者的剂量肌肉注射6天。每4周重复一次这种治疗。
结果，该方案在接受B16黑色素瘤移植的小鼠中显示出相加或协同的抗肿瘤作用。在临床研究中，37例先前未接受治疗的III期或IV期宫颈癌患者和23例复发性宫颈癌患者的缓解率分别为83.8%和60.9%。剂量限制因素是骨髓毒性，但其是可耐受的。其他毒性作用轻微，且无死亡病例。
基于这些结果，认为该联合方案值得在晚期或复发性宫颈癌患者中进行III期对比研究进行评估。
