Dose intensity for bolus versus infusion chemotherapy administration: review of the literature for 27 anti-neoplastic agents.
Dose intensity for bolus versus infusion chemotherapy administration: review of the literature for 27 anti-neoplastic agents.
复制标题
推注与输注化疗给药的剂量强度：27 种抗肿瘤药物的文献综述。
作者：
J. Lokich;N. Anderson
问题
抗肿瘤药物的剂量强度（DI）和最大耐受剂量（MTD）被认为是实现最佳治疗效果的关键因素。这些因素中的每一个都可能受到给药时间表的影响，特别是输注或推注给药。
目标
回顾所选抗肿瘤药物的文献，以分析推注与输注给药方案的相对 DI 和 MTD。
方法
抗代谢药物类别化疗药物推注和输注的临床报告；烷化剂；抗生素；收集植物生物碱和铂类似物，重点是建立每个周期的 MTD 和 DI 的第一阶段研究。输注时间表被定义为连续肠胃外给药超过24小时，或者在某些情况下，每天推注给药一小时，持续3至5天。推注时间表被定义为几分钟至 24 小时内的给药，并且在某些情况下还包括每日给药。
结果
对于抗代谢药物，相对于推注给药，输注方案通常会降低 MTD 和 DI，但对于 5-FU，MTD 和 DI 都会增加。对于烷化剂和铂类似物，推注和输注输送的 MTD 和 DI 通常是相当的；但输注给药会导致塞替派和异环磷酰胺的 MTD 略有增加，MTD 的增加取决于输注的持续时间。对于抗生素和植物生物碱，输注给药的 MTD 和 DI 与具体药剂和输注持续时间相关，是可变的，并且可以增加、减少或与推注方案的 MTD 相当。
结论
大多数通过推注与输注方案施用的细胞毒性药物的 MTD 和 DI 是不可预测且可变的，并且受输注持续时间和治疗周期之间的间隔（例如三周与四周的间隔）的影响。塞替派、5-FU 和 VM26（后者特别适用于白血病）的输注给药后，MTD 和 DI 显着增加，而抗代谢药 FUDR、ara-C、甲氨蝶呤和 6MP 的 MTD 和 DI 显着降低。对于大多数其他药物和所有四种药物类别，MTD 和 DI 相对可比，但对于异环磷酰胺和托泊替康，输注持续时间决定 MTD 和 DI 相对于推注给药是否增加、减少或保持相同。细胞因子的使用可能会显着改变 MTD 和 DI，特别是对于推注给药，因为剂量限制性毒性对于许多药物来说是血液学的。
PROBLEM
The dose intensity (DI) and the maximum tolerated dose (MTD) of anti-neoplastic agents is assumed to be a critical factor for achieving optimal therapeutic benefit. Each of these factors may be influenced by the schedule of drug administration, specifically infusional or bolus delivery.
OBJECTIVE
To review the literature for selected antineoplastic drugs to analyze the relative DI and MTD for bolus vs. infusional administration schedules.
METHODS
Clinical reports of bolus and infusional delivery of chemotherapeutic drugs in the categories of antimetabolites; alkylating agents; antibiotics; plant alkaloids and platinum analogues were collected focusing on phase I studies establishing the MTD per cycle and the DI. Infusional schedules were defined as continuous parenteral administration for more than 24 hours or, in some instances, daily bolus dosing for one hour for 3 to 5 days. Bolus schedules were defined as administration over minutes up to 24 hours and also included daily dosing in some cases.
RESULTS
For antimetabolites, the infusional schedule generally decreases the MTD and DI relative to bolus administration but for 5-FU, the MTD and DI both increase. For alkylating agents and the platinum analogues, the MTD and DI for bolus and infusional delivery are generally comparable; but infusional administration results in a slightly increased MTD for thiotepa and for ifosfamide, the MTD is increased depending upon the duration of the infusion. For the antibiotics and the plant alkaloids, the MTD and DI of infusional administration is variable related to the specific agent and the infusion duration and may be increased, decreased or comparable to the MTD of bolus schedules.
CONCLUSIONS
The MTD and DI for most cytotoxic agents administered by bolus versus infusional schedules is unpredictable and variable and is influenced by the infusion duration and the interval between treatment cycles (for example three versus four week intervals). The MTD and DI increase substantially with infusional delivery for thiotepa, 5-FU and VM26 (the latter in leukemia specifically) and decrease substantially for the antimetabolites FUDR, ara-C, methotrexate and 6MP. For most other agents and in all four drug categories, the MTD and DI are relatively comparable although for ifosfamide and topotecan, the duration of infusion determines whether the MTD and DI increases, decreases or stays the same relative to bolus administration. The use of cytokines may substantially change the MTD and DI especially for bolus administration since dose limiting toxicity is hematologic for many agents.
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通过负荷剂量和连续输注方案对磷酸氟达拉滨进行 I 期临床研究。
DOI：
10.1093/jnci/80.6.447
发表时间：
1988
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Leiby,JM;Grever,MR;Staubus,AE;Neidhart,JA;Malspeis,L
通讯作者：
Malspeis,L
连续输注替尼泊苷的临床药效学：全身暴露作为 I 期试验中反应的决定因素。
DOI：
10.1200/jco.1987.5.7.1007
发表时间：
1987
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Rodman,JH;Abromowitch,M;Sinkule,JA;Hayes,FA;Rivera,GK;Evans,WE
通讯作者：
Evans,WE
影响因子：
45.3
作者：
HOCHSTER, H;LIEBES, L;BLUM, RH
通讯作者：
BLUM, RH
DOI：
--
发表时间：
1983
期刊：
Cancer treatment reports
影响因子：
--
作者：
Garnick,MB;Weiss,GR;SteeleJr,GD;Israel,M;Schade,D;Sack,MJ;Frei3rd,E
通讯作者：
Frei3rd,E