亚叶酸钙（LV）与5-氟尿嘧啶48小时持续输注联合环磷酰胺和长春瑞滨用于转移性乳腺癌预处理患者的剂量递增研究。

A dose escalation study of leucovorin (LV) and 48-hour continuous infusion of 5-fluorouracil in combination with cyclophosphamide and vinorelbine in pretreated patients with metastatic breast cancer.

作者信息

Kouroussis Charalambos, Kalbakis Konstantinos, Androulakis Nikolaos, Agelaki Sophia, Vamvakas Lambros, Malas Konstantinos, Souglakos John, Vardakis Nikolaos, Georgoulias Vassilis

机构信息

Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece.

出版信息

Anticancer Res. 2004 Nov-Dec;24(6):4217-21.

PMID:15736475

Abstract

PURPOSE

To determine the maximum tolerated doses (MTD) and dose-limiting toxicities (DLTs) of vinorelbine (VNR) with fixed doses of cyclophosphamide (CPM) and 5-fluorouracil/leucovorin (5-FU/LV) in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes.

PATIENTS AND METHODS

Eighteen patients with MBC pretreated with anthracyclines and taxanes were enrolled. VNR was administered as a 10-min intravenous infusion (i.v.) on day 1 at escalated doses with CPM 300 mg/m2 i.v. bolus and LV 500 mg/m2 as a 2-hour i.v. infusion, followed by 5-FU 1500 mg/m2 as a 22-hour continuous infusion (c.i.) for two consecutive days. Treatment was repeated every two weeks.

RESULTS

At the dose of VNR 22.5 mg/m2 without rhG-CSF and 25 mg/m2 with rhG-CSF support, the DLT had been reached. Grade 3 or 4 neutropenia occurred in six (33%) patients and in fourteen (27%) cycles with no episode of febrile neutropenia. One (5.5%) patient developed grade 4 thrombocytopenia. Grade 3 neurotoxicity occurred in two patients and grade 2 and 3 asthenia in five (28%).

CONCLUSION

The recommended doses for phase II studies are 20 mg/m2 for VNR (22.5 mg/m2 with rhG-CSF support) and 300 mg/m2 for CPM on day 1, with 500 mg/m2 for LV and 1500 mg/m2 for 5-FU on days 1 and 2.

摘要

目的

确定在接受过蒽环类药物和紫杉烷类药物治疗的转移性乳腺癌（MBC）患者中，长春瑞滨（VNR）与固定剂量的环磷酰胺（CPM）和5-氟尿嘧啶/亚叶酸钙（5-FU/LV）联合使用时的最大耐受剂量（MTD）和剂量限制性毒性（DLT）。

患者和方法

招募了18例接受过蒽环类药物和紫杉烷类药物治疗的MBC患者。第1天，VNR以递增剂量进行10分钟静脉输注（i.v.），同时CPM 300 mg/m²静脉推注，LV 500 mg/m²进行2小时静脉输注，随后5-FU 1500 mg/m²进行22小时持续输注（c.i.），连续两天。每两周重复一次治疗。

结果

在未使用重组人粒细胞集落刺激因子（rhG-CSF）时VNR剂量为22.5 mg/m²以及使用rhG-CSF支持时剂量为25 mg/m²的情况下，达到了DLT。6例（33%）患者出现3级或4级中性粒细胞减少，14个周期（27%）出现该情况，且无发热性中性粒细胞减少事件。1例（5.5%）患者出现4级血小板减少。2例患者出现3级神经毒性，5例（28%）患者出现2级和3级乏力。