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研究生:張歐群
研究生(外文):CHANGOU, CHUN AUSTIN
論文名稱:PHY906與Capecitabine於肝癌的藥理與臨床二期綜合療法研究
論文名稱(外文):Combination Therapy of PHY906 plus Capecitabine in Hepatocellular Carcinoma, a Phase II Clinical Trial Study.
指導教授:施景文施景文引用關係
指導教授(外文):SHIH, JING-WEN
口試委員:施景文閻雲吳天元曾若嘉李崑豪
口試委員(外文):SHIN, JING-WENYen, YunWU, Tien-YuanTSENG, RUO-CHIALEE, KUEN-HAUR
口試日期:2023-06-21
學位類別:博士
校院名稱:臺北醫學大學
系所名稱:癌症生物學與藥物研發博士學位學程
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2023
畢業學年度:111
語文別:英文
論文頁數:55
中文關鍵詞:PHY906
外文關鍵詞:PHY906
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PHY906 是一種由四種草藥組成的傳統中藥,已具有 1800 多年的歷史用於 緩解各種症狀,如腹部絞痛、發燒、頭痛、嘔吐、口渴和腹瀉。最近的研 究顯示,它還具有多種可能的使用,例如增強化學治療劑和靶向劑的抗腫 瘤作用,顯示出 PHY906 用於癌症治療的潛力。在之前的美國 I/II 期臨床 試驗中,接受 PHY906 配合 Ca[ecitabine 治療的晚期肝細胞癌患者獲得了良 好的臨床結果。這些有未來發展性的發現突顯了 PHY906 作為 HCC 有效輔 助療法的潛力。為了進一步研究 PHY906 的療效,我們在台灣對 HCC 患者 進行了 II 期臨床試驗,旨在驗證這些先前的發現。在通過更大規模的患者 隊列中評估 PHY906 的療效,我們可以更全面地了解其在 HCC 治療中的潛 在治療價值。這項研究的結果可能有助於為 HCC 以及其他類型的癌症患者 開發更有效和個性化的治療策略。
PHY906 is a traditional Chinese medicine comprising four herbs that has been used for over 1800 years to alleviate various symptoms such as abdominal cramps, fever, headache, vomiting, thirst, and diarrhea. Recent studies have shown that it also has the potential to enhance the antitumor effects of a variety of chemotherapeutic and targeting agents, indicating its potential in cancer treatment. In a previous U.S. phase I/II clinical trial, patients with advanced hepatocellular cancer who received PHY906 in combination with capecitabine experienced favorable clinical outcomes. These promising findings highlight the potential of PHY906 as an effective adjunct therapy for HCC. To further investigate the efficacy of PHY906, our Phase II clinical trial involving HCC patients in Taiwan aims to validate these previous findings. By evaluating the effects of PHY906 in a larger cohort of patients, we can gain a more comprehensive understanding of its potential therapeutic value in HCC treatment. The results of this study may contribute to the development of more effective and personalized treatment strategies for patients with HCC, as well as other types of cancer.
Abstract (Chinese) ........................................................................................... I
Abstract (English) ............................................................................................ I
Acknowledgement ........................................................................................... III
Contents ......................................................................................................... IV
List of Figures .................................................................................................. V
List of Tables ................................................................................................... vIi

Chapter I
Introduction ..................................................................................................... 8
1. Ongoing threat and current treatment options of HCC ............................... 8
2. Treatment option 1: Sorafenib ..................................................................... 8
3. Treatment option 2: Lenvatinib ................................................................... 9
4. Treatment option 3: Capecitabine .............................................................. 10
5. The new hope: PHY906 .............................................................................. 10

Chapter II
Materials and Methods ................................................................................... 12
1. Patient and Method ..................................................................................... 12
2. Patient selection and evaluation ................................................................. 12
3. Treatment plan and compliance .................................................................. 14
4. Evaluation of toxicity ................................................................................... 14
5. Evaluation of response ................................................................................ 15
6. Quality of life (QoL) ..................................................................................... 16
7. Statistical analysis ....................................................................................... 16

Chapter III
Results ............................................................................................................ 17
1. Treatment .................................................................................................... 17
2. Patient demographics ................................................................................. 18
3. Most common drug-related adverse events................................................ 18
4. Objective response ..................................................................................... 20
5. Hepatitis status, liver disease classification, and treatment cycles ........... 20

Chapter IV
Discussion ...................................................................................................... 22

Chapter V
Conclusion ..................................................................................................... 26

Figures and Legends
Figure 1. PHY906 and Capecitabine combinational treatment schedule for Hepatocellular Carcinoma (HCC)
....................................................................................................................... 32
Figure 2. Most common drug-related adverse events .................................. 33
Figure 3. Kaplan-Meier plots of overall survival of patients .......................... 34
Figure 4. HBV may enhance clinical outcome ............................................... 36
Figure 5. Initial AFP level and number of treatments had direct impact on patient overall survival
..................................................................................... ................................ 38
Figure 6. Quality of life score for PHY906 and Capecitabine therapy .......... 39


Tables
Table I. Summer of demographics and baseline characteristics of patients .. 40
Table II. Adverse events incidence by body system ....................................... 41
Table III. Adverse events (by patient, N=30) ................................................... 42
Table IV. Study drug-related adverse event (by patients, N=39) .................... 43
Table V. Tumor response in HCC patients ...................................................... 44

References .................................................................................................... 45
Publication .................................................................................................... 50
Additional Publications ................................................................................. 51
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