A Dose Response Analysis For Cytotxic Drugs (Ⅰ) Alpha,Beta,Gamma Model

化學抗癌藥物的劑量反應曲線分析：(Ⅰ)α．β．γ模式的創立

季匡茟(Kwan-Hwa Chi) ； Jack.F.Fowler ； 陳光耀(Kuang-Y Chen) ； Timothy J.Kinsella

《放射治療與腫瘤學》 1卷1期 (1994/03) Pp. 1-12

https://doi.org/10.6316/TRO/199401(1)1

摘要

傳統上化學抗癌藥物的給法常是間隔性的給予一個大劑量，待治療的副作用恢復後再級予下一劑量，其間隔多為3至6週不等，視藥物不同而異。然而，臨床報告發現有許多藥物的療效以及其副作用，會因給藥的間隔方法而大有不同。如何能事先預測某一藥物以那一種給藥方法能產生最大的毒殺作用，是本研究的目的。
首先以肪胱癌細胞株作為實驗細胞，作出5種化學藥物CDDP，TDDP，BLM，VP-16及BCNU的細胞——藥物劑量反應曲線。再以數學模式S=exp [-(αD+βD^2+rD^3)]，由電腦算出各個參數及模擬圖形，並導出一系列的數學演算來解釋劑量反應曲線的動力意義。此模式不僅可模擬藥物的劑量反應曲線，更架起了化學治療與放射治療之間的桥樑。本文先報告此研究的第一部分——模式的創立。

並列摘要

We tentatively investigate the hypothesis that the effect of repeated small doses of chemotherapeutic drugs can be estimated from the shape of in vitro cell survival curves of human cancer cells, provided that this shape is the same for each dose administered. Drugs with different shapes of survival curves will require differently planned dose scheduling. A human bladder cancer cell line (647V) was used in these preliminary experiments.
The clonogenic survival curves for 5 different anticancer drugs (CDDP, TDDP, BLM, VP-16, BCNU) for 647V cells were determined experimentally and found to fit a polynomial survival curve model over a limited range, the α, β, γ model, with s=exp[-(αD+βD2 +γD3)], where D is dose, and is a function of both concentration and time. Equations are derived for schedule changes and clonogenic kill calculations. This approach provides a new method of optimizing dosage schedules. It also provides a common language between medical oncologists and radiation oncologists in survival curve analysis. Although these preliminary experiments were limited to one human cancer cell line and five chemotherapeutic drugs, the concept appears to be worth testing further. We are now reporting the first psrt of this research work-the modeling.

並列關鍵字

Anticancer ； antineoplastic ； drugs ； chemotherapy ； pharmacodynamics ； linearquadratic model