González-Martín Antonio, Crespo Carmen, García-López José Luis, Pedraza Manuela, Garrido Pilar, Lastra Enrique, Moyano Alfredo
Medical Oncology Service, Alcala de Henares University, Madrid, 28034, Spain.
Gynecol Oncol. 2002 Mar;84(3):368-73. doi: 10.1006/gyno.2001.6508.
The aim of this study was to determine the activity and toxicity of a vinorelbine and ifosfamide combination in platinum-resistant advanced ovarian cancer.
Patients were treated with ifosfamide (2 g/m(2)/day) infused over 1 h x 3 days (with mesna uroprotection) and vinorelbine (30 mg/m(2)) on days 1 and 8. Treatment was repeated on a 21-day schedule. In order to avoid unacceptable toxicity in this subset of patients where the chemotherapy is mainly palliative, the Bryant and Day two-stage phase II trial design incorporating toxicity considerations was chosen. A cutoff point for the response rate (10%) and for severe toxicity (25%) was established for the first 14 patients.
Between February 1997 and December 1998, 11 paclitaxel and platinum-resistant patients and 1 potentially platinum-sensitive patient were treated. Five patients (41%) experienced grade 3-4 central nervous toxicity requiring hospital admission. In accordance with the Bryant and Day design, the study was stopped early because greater than 25% of the first 14 patients developed grade 3-4 neurotoxicity. A retrospective review of clinical characteristics of these patients showed at least one well-known risk factor associated with ifosfamide central toxicity. Hematological toxicity was common, mainly grade 4 neutropenia, which was observed in all but 1 patient, usually of short duration, and there were 4 episodes of neutropenic fever. Ten patients were evaluated for response. Two complete responses and 1 partial response according to CA-125 criteria were observed.
This combination may be active in platinum-resistant ovarian cancer but the high toxicity encountered, principally neurotoxicity in those with large central pelvic masses, means that further studies with this schedule may not be warranted.
本研究旨在确定长春瑞滨与异环磷酰胺联合方案对铂耐药晚期卵巢癌的活性及毒性。
患者接受异环磷酰胺（2 g/m²/天）静脉滴注1小时，共3天（同时给予美司钠尿路保护），并于第1天和第8天给予长春瑞滨（30 mg/m²）。治疗每21天重复一次。为避免在主要采用姑息性化疗的这部分患者中出现不可接受的毒性，选择了纳入毒性考量的Bryant和Day两阶段II期试验设计。为前14例患者确定了缓解率（10%）和严重毒性（25%）的截断点。
1997年2月至1998年12月，治疗了11例对紫杉醇和铂耐药的患者以及1例可能对铂敏感的患者。5例患者（41%）出现3 - 4级中枢神经毒性，需要住院治疗。根据Bryant和Day设计，该研究提前终止，因为前14例患者中有超过25%出现3 - 4级神经毒性。对这些患者临床特征的回顾性分析显示，至少有一个与异环磷酰胺中枢毒性相关的已知危险因素。血液学毒性很常见，主要是4级中性粒细胞减少，除1例患者外均有发生，通常持续时间较短，有4次中性粒细胞减少性发热发作。对10例患者进行了疗效评估。根据CA - 125标准观察到2例完全缓解和1例部分缓解。
该联合方案可能对铂耐药卵巢癌有活性，但所遇到的高毒性，主要是盆腔中央有大肿块患者的神经毒性，意味着可能无需对该方案进行进一步研究。
