Campisi C, Fabi A, Papaldo P, Tomao S, Massidda B, Zappala A, Ionta M T, Cognetti F
National Research Council, Institute of Biomedical Technologies, Rome, Italy.
Ann Oncol. 1998 May;9(5):565-7. doi: 10.1023/a:1008221109364.
Vinorelbine (VNR) is highly active in metastatic breast cancer (MBC) and has shown an overall response rate of 40%-50% as first-line treatment. In vitro, a synergy has been observed between this drug and ifosfamide (IFX). In addition, the pharmacokinetics of IFX suggest that it may have greater activity when given by continuous-intravenous infusion (c.i.v.i.). The aim of this study was, therefore, to assess the antitumor efficacy and toxicity of the combination of bolus VNR and c.i.v.i. IFX as second-line therapy in anthracycline-resistant breast cancer patients.
Forty-two patients with MBC who had already received anthracycline-based chemotherapy were treated with a regimen consisting of IFX, by c.i.v.i. for 72 hours and bolus VNR. The courses were repeated every three weeks for a maximum of eight cycles. Four dose intensification steps were planned: IFX, 1.5 g/m2 on days 1-3 + VNR, 30 mg/m2 on day 1 (six patients); IFX, 2 g/m2 on days 1-3 + VNR, 25 mg/m2 on day 1 (six patients); IFX, 1.8 mg/m2 on days 1-3 + VNR, 25 mg/m2 on days 1 and 8 (six patients); IFX, 2 g/m2 on days 1-3 + VNR, 25 mg/m2 on days 1 and 8 (24 patients). Sodium-2-mercaptoethane sulfonate (mesna) was associated with IFX at an infusion ratio of 1:1 and, once the infusion was completed, per os every four hours for three times.
All of the 42 patients entered were assessable for toxicity, and 41 of them for response. Neutropenia was the most frequently-occurring toxicity, but only five patients at the highest dose level (11.9%) presented grade 4, and none of those at the first three steps. Other significant toxic effects were mild (only grade I-II). The median relative dose intensity was 95% at the highest dose level and all of the treatments were administered on an out-patient basis. The overall response rate was 36.5% with a CR rate of 4.8% (two of 41 patients, all at the highest dose level) and a PR rate of 31.7% (13 of 41 patients). The median response duration was 7.0 months (range 2-13 months).
The present phase I-II study shows that the IFX and VNR combination is an active and well-tolerated treatment in MBC and provides an alternative to taxanes for patients previously treated with anthracyclines.
长春瑞滨（VNR）对转移性乳腺癌（MBC）具有高度活性，作为一线治疗显示出40%-50%的总缓解率。在体外，已观察到该药物与异环磷酰胺（IFX）之间存在协同作用。此外，IFX的药代动力学表明，持续静脉输注（c.i.v.i.）给药时可能具有更高的活性。因此，本研究的目的是评估大剂量VNR与c.i.v.i. IFX联合作为蒽环类耐药乳腺癌患者二线治疗的抗肿瘤疗效和毒性。
42例已接受蒽环类化疗的MBC患者接受了由IFX（c.i.v.i. 72小时）和大剂量VNR组成的治疗方案。疗程每三周重复一次，最多进行8个周期。计划了四个剂量强化步骤：IFX，第1-3天1.5 g/m² + VNR，第1天30 mg/m²（6例患者）；IFX，第1-3天2 g/m² + VNR，第1天25 mg/m²（6例患者）；IFX，第1-3天1.8 mg/m² + VNR，第1天和第8天25 mg/m²（6例患者）；IFX，第1-3天2 g/m² + VNR，第1天和第8天25 mg/m²（24例患者）。2-巯基乙烷磺酸钠（美司钠）与IFX以1:1的输注比例联合使用，输注完成后，每4小时口服一次，共三次。
所有42例入组患者均可评估毒性，41例可评估疗效。中性粒细胞减少是最常见的毒性，但仅最高剂量水平的5例患者（11.9%）出现4级，前三步剂量水平的患者均未出现。其他显著的毒性作用较轻（仅为I-II级）。最高剂量水平的中位相对剂量强度为95%，所有治疗均在门诊进行。总缓解率为36.5%，完全缓解率为4.8%（41例患者中的2例，均在最高剂量水平），部分缓解率为31.7%（41例患者中的13例）。中位缓解持续时间为7.0个月（范围2-13个月）。
本I-II期研究表明，IFX与VNR联合在MBC中是一种活性良好且耐受性好的治疗方法，为先前接受过蒽环类治疗的患者提供了紫杉烷类药物之外的另一种选择。
