| 摘要(英) |
It has become recently an important issue to develop a combination of two drugs for cancer treatment. However, the toxicity of the combined drugs may be enhanced when individual drugs possibly have overlapping dose-limiting toxicities (DLTs). In this thesis, model-based designs are constructed to find the maximum tolerated dose combination (MTC) at which the probability of DLT is closest to the target toxicity probability (TTP). To quickly collect information to facilitate the application of the model-based procedures, the start-up phase is designed. The dose combination-toxicity relationship is then described by the Finney or logistic model incorporating interaction between two individual drugs. The models are then employed into the Keyboard combined drug design for dose combination escalation/de-escalation and MTC estimation. Therefore, the proposed design is called the model-based Keyboard combined drug designs. We also modify the proposed designs for the setting with late-onset toxicity. Finally, a simulation study is conducted to investigate the performance of the proposed designs relative to some designs in the literatures under a variety of toxicity probability scenarios on the correct MTC selection and toxicity to patients. The simulation results show that the proposed model-based Keyboard combined drug designs outperform the model-based design or the original Keyboard combined drug design. |
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黃彥文，「鑑別最佳添加藥物劑量的兩階段早期臨床試驗設計」，國立中央大學，碩士論文，民國 108 年。 |
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