| 摘要: | 摘要
背景：Irinotecan與Oxaliplatin為轉移性大腸直腸癌第一線用藥，分別合併5-Fluorouracil使用可大幅度提高患者存活率到二十個月，而Irinotecan與Oxaliplatin臨床上使用大部分患者會出現腹瀉、噁心嘔吐、白血球低下等副作用，西藥的化療前給藥對副作用的幫助有限，病患常常會因為嚴重副作用而拒絕治療；香砂六君子湯為中醫治療此類腸胃道症狀良好的方劑，且藥性溫和，本實驗選擇香砂六君子湯為實驗用藥，針對化療後胃腸道副作用做療效和安全性評估。
病人與研究方法：本研究採中西醫結合治療，研究設計採用多中心隨機雙盲試驗，納入慈濟醫院台中分院、台北分院以及花蓮總院大腸直腸癌症第三期與第四期的接受FOLFIRI (Irinotecan + 5-FU) 與FOLFOX (Oxaliplatin + 5-FU)化療患者接受試驗，受試者分成兩組分別接受香砂六君子湯以及安慰劑八週的治療，而試驗組和對照組使用相同的化療前給藥，研究期間，兩週一次以Common Terminology Criteria for Adverse Events Version 3.0(CTCAE)為評估副作用標準並觀察其理學檢查及抽血檢查變化，同時以大腸直腸癌生活品質問卷評估，以病人自覺報告結果觀察其生活品質是否改善，以評估香砂六君子湯是否可以改善大腸直腸癌化學治療的副作用。
結果：慈濟醫院台中分院、台北分院以及花蓮總院大腸直腸癌症第三期與第四期的化療患者，共67人納入試驗，受試者基本資料，兩組年齡比、男女比、血液檢驗、生活品質量表、第三期與第四期相比和FOLFIRI 與FOLFOX相比並無統計上的相異；在以CTCAE評估用藥後其症狀層級，兩組用藥之後並無統計學上的顯著差異；在服用藥物兩週後，腹瀉在實驗組上有改善，而對照組則沒有改善，兩組之間p值接近0.05，顯示香砂六君子湯使用初期對化療所引起的腹瀉有改善的作用。在服用藥物四週後，生活品質量表的整體健康狀況(Global health status / QoL)方面，對照組有惡化的變化，在統計學上有顯著差異，而實驗組則沒有明顯變化，而兩組之間在統計學上有顯著差異；便秘、疲倦、疼痛、失眠、呼吸困難與腸胃症狀在實驗組上有改善，而對照組則沒有改善，兩組之間有統計學上的差異；RBC、hematocrit對照組均有減少，然而實驗組卻沒有統計學上的差異。香砂六君子湯沒有CBC、肝功能和腎功能方面的不良反應；同時所有的不良反應都屬化療本身的副作用與癌症本身的病程，均與中藥和安慰劑無關，試驗組與對照組發生不良反應的比例並無統計上的差異。
結論：本試驗為多中心雙盲隨機臨床試驗，雖然香砂六君子湯無法在化學治療毒性評分表(CTCAE)上在統計上證實有效，但在生活品質問卷中，香砂六君子湯在整體健康狀況、腸胃症狀、便秘、腹瀉、情緒功能、疲倦、疼痛、失眠、呼吸困難與貧血的改善與安慰劑相比在統計學上有顯著差異，同時也證實其為一相當安全的方劑。
Abstract
Introduction
Irinotecan and oxaliplatin is the first-line chemotherapy agent for metastatic colorectal cancer. 5-fluorouracil (FU) in combination with irinotecan and oxaliplatin can increase the medium survival of metastatic colorectal cancer patients to more than 20 months. The most frequent toxicity of irinotecan and oxaliplatin were diarrhea, nausea, vomiting and diarrhea. Chinese herbal medicine (CHM) is a common complementary therapy used by patients with cancer for reduction of chemotherapy-induced toxic effects. In this multi-center prospective randomized controlled trial, we evaluated the efficacy and safety of Chinese medicine--- xiang sha liu jun zi tang in the treatment of the gastro-intestinal side effect of chemotherapy for metastatic colorectal cancer
Patients and methods
Patients with stage 3 or 4 colorectal cancer who required chemotherapy were eligible for the study. Enrolled patients were randomly assigned to 2 groups. Patients received either xiang sha liu jun zi tang or placebo capsules with a corresponding serial number. The primary end points were gastro-intestinal toxicity according to the National Cancer Institute Common Toxicity Criteria Version 3.0(CTCAE). The secondary end points were hematologic
toxicity and questionnaire EORTC QLQ-C30 and EORTC QLQ CR-38.
Results
67 patients were accrued with 3 screen failure and 32 patients in the xiang sha liu jun zi tang group and 32 patients in the placebo group . Patient characteristics of the two groups were similar. There were no significant differences in gastro-intestinal toxicities(CTCAE) between the xiang sha liu jun zi tang and placebo groups. Of the cancer patient questionnaire EORTC QLQ-C30 and EORTC QLQ CR-38, there were significant improvement of global health status, diarrhea, constipation, fatigue, pain, insomnia, dyspnea, anemia and gastro-intestinal symptoms. There were decrease of RBC and hematocrit in the placebo group but not in the xiang sha liu jun zi tang group. The adverse effects were all caused by the chemotherapeutic agent and none was related to xiang sha liu jun zi tang.
Conclusion
The Chinese medicine xiang sha liu jun zi tang does not reduce the gastro-intestinal toxicity(CTCAE) associated with chemotherapy for metastatic colorectal cancer. Xiang sha liu jun zi tang, however, does have a significant impact on control of global health status, diarrhea, constipation, fatigue, pain, insomnia, dyspnea, anemia and gastro-intestinal symptoms. And it is also a safe regimen for the patients. |
