A multicentre randomised phase II study of carboplatin in combination with gemcitabine at standard rate or fixed dose rate infusion in patients with advanced stage non-small-cell lung cancer
A multicentre randomised phase II study of carboplatin in combination with gemcitabine at standard rate or fixed dose rate infusion in patients with advanced stage non-small-cell lung cancer
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DOI：
10.1093/annonc/mdl084
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发表时间：
2006-07-01
影响因子：
50.5
通讯作者：
Goh, B. C.
中科院分区：
文献类型：
--
作者：
Soo, R. A.;Wang, L. Z.;Goh, B. C.
背景资料：细胞内吉西他滨三磷酸（dFdCTP）水平可以通过以固定剂量率输注施用吉西他滨来优化。未接受化疗的晚期非小细胞肺癌（NSCLC）患者随机接受吉西他滨治疗，固定剂量率为吉西他滨750 mg/m2，持续75分钟（A组）或吉西他滨1000 mg/m2，持续30分钟（B组）每三周周期的第1天和第8天。在每个周期的第1天，在两个治疗组中给予AUC为5的卡铂。终点是血浆和细胞内吉西他滨的活性、耐受性和药代动力学。A组和B组的缓解率分别为34%和42%。两个治疗组的毒性和生活质量评分相似。A组的平均血浆Cmax（吉西他滨）和平均dFdCTP AUC分别为20.8 μ M +/- 17.2 μ M和35 079 +/- 18 216 μ M*min，B组分别为41.2 +/- 13.9 μ M和32 249 +/- 11 267 μ M*min。在B组中达到dFdCTP饱和，但在A组中未达到。结论：A组中dFdCTP蓄积的饱和性表明，与30分钟输注相比，使用固定速率输注实现吉西他滨的最佳递送。固定剂量率吉西他滨是有效可行的，支持吉西他滨在晚期NSCLC中的固定剂量率概念。然而，这需要较长的输注时间，并涉及相关的较高成本。
Background: Intracellular gemcitabine triphosphate (dFdCTP) levels can be optimised by administering gemcitabine at a fixed dose rate infusion.Patients and methods: Patients with chemonaive advanced non-small cell lung cancer (NSCLC) were randomised to receive gemcitabine at a fixed dose rate gemcitabine 750 mg/m(2) over 75 min (arm A) or gemcitabine 1000 mg/m(2) over 30 min (arm B) on days 1 and 8 every three week cycle. Carboplatin at AUC of 5 was administered in both treatment arms on day 1 of each cycle. End points were activity, tolerability and pharmacokinetics of plasma and intracellular gemcitabine.Results: 76 patients were randomised. Response rate was 34% in arm A and 42% in arm B. Toxicity and quality of life scores were similar for both treatment arms. Mean plasma Cmax(gemcitabine) and mean dFdCTP AUC in arm A was 20.8 mu M +/- 17.2 mu M and 35 079 +/- 18 216 mu M*min respectively and in arm B, 41.2 +/- 13.9 mu M and 32 249 +/- 11 267 mu M*min respectively. dFdCTP saturation was reached in Arm B but not in Arm A.Conclusion: The saturability of dFdCTP accumulation in Arm A suggests optimal delivery of gemcitabine is achieved using fixed rate infusion compared to 30-min infusion. Fixed dose rate gemcitabine is active and feasible, supporting the concept of fixed dosing rate of gemcitabine in advanced NSCLC. However, this entails a longer infusion time with associated higher costs involved.