Papadimitriou C A, Kouroussis C, Moulopoulos L A, Vlahos G, Rodolakis A, Kiamouris C, Diakomanolis E, Gika D, Michalas S, Dimopoulos M A
Department of Clinical Therapeutics, Alexandra Hospital, Athens University School of Medicine, Tatoiou 146, 146 71 Nea Erythrea, Athens, Greece.
Cancer. 2001 Oct 1;92(7):1856-63. doi: 10.1002/1097-0142(20011001)92:7<1856::aid-cncr1702>3.0.co;2-j.
The combination of paclitaxel with a platinum analogue is the preferred chemotherapy regimen in the treatment of advanced epithelial ovarian carcinoma. The alkylating agent ifosfamide has shown activity in refractory or recurrent ovarian cancer. We conducted a Phase II study with the combination of ifosfamide, paclitaxel, and cisplatin for the treatment of newly diagnosed patients with advanced, suboptimally debulked ovarian carcinoma.
Thirty-five consecutive patients with advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage III or IV) and residual disease larger than 2 cm after staging laparotomy and cytoreductive surgery were treated with paclitaxel, 175 mg/m(2), as a 3-hour intravenous infusion on Day 1, cisplatin 75 mg/m(2) intravenously over 2 hours on Day 2, and ifosfamide 1500 mg/m(2) intravenously over 1 hour on Days 1-3 (with sodium 2-mercaptoethane sulfonate [MESNA] uroprotection). Courses were administered every 3 weeks on an outpatient basis. Granulocyte-colony stimulating factor was given at a dose of 5 microg/kg/day on Days 7-11.
Among 26 patients with measurable disease, 22 (85%) achieved an objective response including 15 complete and 7 partial responses. With a minimum follow-up of 46 months, the median overall survival was 52.8 months (range, 5.3-56.6+ mos), whereas the median time to progression for all patients was 22.2 months. The median remission duration for women with measurable disease who responded to treatment was 12.6 months. The treatment was tolerated relatively well without toxic deaths; the most common toxicity was Grade 3 or 4 neutropenia that occurred in 42% of patients. Significant peripheral neuropathy (Grade 2 or higher) developed in 35% of patients.
The combination of ifosfamide, paclitaxel, and cisplatin is a well-tolerated outpatient regimen with significant activity in the treatment of newly diagnosed FIGO Stage III or IV epithelial ovarian carcinoma. Further evaluation is justified to clearly define the role of ifosfamide as an additional agent to the current platinum and paclitaxel regimens.
紫杉醇与铂类类似物联合是晚期上皮性卵巢癌治疗的首选化疗方案。烷化剂异环磷酰胺已显示出对难治性或复发性卵巢癌有活性。我们开展了一项II期研究，采用异环磷酰胺、紫杉醇和顺铂联合治疗新诊断的晚期、减瘤不充分的卵巢癌患者。
35例连续的晚期卵巢癌患者（国际妇产科联盟[FIGO] III期或IV期），在分期剖腹手术和肿瘤细胞减灭术后残留病灶大于2 cm，接受紫杉醇175 mg/m²，于第1天静脉滴注3小时，顺铂75 mg/m²于第2天静脉滴注2小时，异环磷酰胺1500 mg/m²于第1 - 3天静脉滴注1小时（同时给予美司钠[MESNA]进行尿路保护）。每3周门诊给药1个疗程。在第7 - 11天给予粒细胞集落刺激因子，剂量为5 μg/kg/天。
在26例可测量病灶的患者中，22例（85%）获得客观缓解，包括15例完全缓解和7例部分缓解。最短随访46个月，中位总生存期为52.8个月（范围5.3 - 56.6 +个月），而所有患者的中位疾病进展时间为22.2个月。对治疗有反应的可测量病灶女性患者的中位缓解持续时间为12.6个月。该治疗耐受性相对良好，无毒性死亡；最常见的毒性是3或4级中性粒细胞减少，发生在42%的患者中。显著的周围神经病变（2级或更高）发生在35%的患者中。
异环磷酰胺、紫杉醇和顺铂联合是一种耐受性良好的门诊治疗方案，对新诊断的FIGO III期或IV期上皮性卵巢癌有显著活性。进一步评估以明确异环磷酰胺作为当前铂类和紫杉醇方案额外药物的作用是合理的。
