Bensinger William I, Buckner C Dean, Lilleby Kathy, Holmberg Leona, Storb Rainer, Slattery John T
Fred Hutchinson Cancer Research Center, and University of Washington School of Medicine Seattle, Wash., USA.
Oncology. 2004;67(5-6):368-75. doi: 10.1159/000082920.
There is evidence that pentoxifylline (PTX) and ciprofloxacin (Cipro) may protect patients from the effects of chemotherapy and radiation, which could allow further drug dose escalation. This study was conducted to determine whether oral and intravenous (IV) PTX and Cipro permits increased dose levels of oral busulfan (BU) with a fixed dose of IV cyclophosphamide (CY) in patients with breast cancer receiving autologous or syngeneic hematopoetic cell transplantation.
Sixty-seven patients received PTX and Cipro with CY of 150 mg/kg and escalating doses of BU. The BU dosing began at 15 mg/kg, escalating in 1 mg/kg increments in groups of 4 patients. If no grade 3 or 4 regimen- related toxicities (RRT) were observed, the next 4 patients were treated at a higher dose.
Excessive RRT was not observed until BU 21 mg/kg was reached. Two patients at this dose level had RRTs and their BU steady-state concentration (Css) were 1,414 and 1,545 ng/ml. At a BU dose of 20 mg/kg , average BU Css 1,280 ng/ml, 0/4 had RRT. Among 10 patients who had BU Css targeted to 1,350 ng/ml, RRTs occurred in 2 (20%).
In this preliminary study with PTX and Cipro, the maximum tolerated dose of BU that can be given with CY (150 mg/kg) was 20 mg/kg, a BU Css of approximately 1,300 ng/ml. A randomized trial is necessary to determine whether PTX and Cipro reduce the toxicities of this regimen.
有证据表明己酮可可碱（PTX）和环丙沙星（Cipro）可能保护患者免受化疗和放疗的影响，这可能允许进一步提高药物剂量。本研究旨在确定在接受自体或同基因造血细胞移植的乳腺癌患者中，口服和静脉注射（IV）PTX及Cipro是否能在静脉注射环磷酰胺（CY）固定剂量的情况下，允许提高口服白消安（BU）的剂量水平。
67例患者接受PTX、Cipro以及150mg/kg的CY，并递增剂量的BU。BU给药起始剂量为15mg/kg，以1mg/kg的增量递增，每组4例患者。如果未观察到3级或4级方案相关毒性（RRT），则接下来的4例患者接受更高剂量治疗。
直到达到21mg/kg的BU剂量时才观察到过多的RRT。此剂量水平的2例患者出现RRT，其BU稳态浓度（Css）分别为1414和1545ng/ml。在20mg/kg的BU剂量下，平均BU Css为1280ng/ml，4例患者中0例出现RRT。在10例将BU Css目标设定为1350ng/ml的患者中，2例（20%）出现RRT。
在这项关于PTX和Cipro的初步研究中，与CY（150mg/kg）联合使用时，BU的最大耐受剂量为20mg/kg，即BU Css约为1300ng/ml。需要进行随机试验来确定PTX和Cipro是否能降低该方案的毒性。
