The Effect of Transarterial Chemoembolization in Combination With Kang’ai Injection on Patients With Intermediate Stage Hepatocellular Carcinoma: A Prospective Study
Abstract:Background: The outcome of patients with intermediate stage hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) remains poor. Search for a more effective therapy is still necessary. Objective: This study aimed to investigate the effect of combining TACE with Kang’ai (KA) injection for treating patients with intermediate stage HCC. Methods: A total of 89 patients with intermediate stage HCC were enrolled and divided into TACE +KA group (n = 48) receiving repeated TACE plus KA inject… Show more
“… 13 , 14 For HCC, many effective fang-ji (formulas) have been clinically proven to retard HCC progression and prevent HCC occurrence. 10 , 15 , 16 , 17 , 18 , 19 , 20 The fang-ji were designed on the TCM theory of disequilibrium of yin and yang and qi and xue . Figure 1 Development of traditional Chinese medicine .…”
Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide. Western medicine and therapies are the primary treatment strategies of hepatocellular carcinoma (HCC), but the general prognosis for HCC patients is still dismal. Under these circumstances, HCC prevention is particularly important. Traditional Chinese medicine (TCM) encompasses a wealth of documented therapeutic resources, and “preventative treatment” is the principle of TCM. In China, TCM has been used for HCC prevention for thousands of years, and has also been demonstrated to be effective for the treatment of HCC in modern China. However, the TCM theory for prevention and treatment of HCC is more widely accepted in China than abroad. In this review, we first summarize the herbs and ancient formulas with therapeutic effects on HCC. We also review the research status of TCM in modern medicine as well as the current obstacles in its development. Finally, we discuss the future of TCM in the context of precision and integrated medicine. After reviewing the literature, we believe that TCM, through ancient development, is an advanced method of cancer treatment with positive curative effects, despite its surrounding controversy. Furthermore, precise analyses and systematic research methods provides novel approaches to modernize TCM for the future.
“… 13 , 14 For HCC, many effective fang-ji (formulas) have been clinically proven to retard HCC progression and prevent HCC occurrence. 10 , 15 , 16 , 17 , 18 , 19 , 20 The fang-ji were designed on the TCM theory of disequilibrium of yin and yang and qi and xue . Figure 1 Development of traditional Chinese medicine .…”
Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide. Western medicine and therapies are the primary treatment strategies of hepatocellular carcinoma (HCC), but the general prognosis for HCC patients is still dismal. Under these circumstances, HCC prevention is particularly important. Traditional Chinese medicine (TCM) encompasses a wealth of documented therapeutic resources, and “preventative treatment” is the principle of TCM. In China, TCM has been used for HCC prevention for thousands of years, and has also been demonstrated to be effective for the treatment of HCC in modern China. However, the TCM theory for prevention and treatment of HCC is more widely accepted in China than abroad. In this review, we first summarize the herbs and ancient formulas with therapeutic effects on HCC. We also review the research status of TCM in modern medicine as well as the current obstacles in its development. Finally, we discuss the future of TCM in the context of precision and integrated medicine. After reviewing the literature, we believe that TCM, through ancient development, is an advanced method of cancer treatment with positive curative effects, despite its surrounding controversy. Furthermore, precise analyses and systematic research methods provides novel approaches to modernize TCM for the future.
“…Bioactive compounds with adequate abundance in herbal injection and favorable PK properties are mostly believed to be responsible for the pharmacological effects and therapeutic e cacy [4]. In the current study, alkaloids and saponins derived from Kang-Ai injection are two classes of bioactive compounds which are likely responsible for the adjuvant therapy of many cancers (Additional le 1: Table S1) [6,8]. After dosing, oxymatrine (A3), matrine (A1), astragaloside IV (B2), ginsenosides Rc (D3), Rd (D2), Rb1 (D5), Rg1 (C6) and Re (C9), all exhibited considerably high levels of systemic exposure (over 1000 nmol/L*h) ( Fig.…”
Section: Discussionmentioning
confidence: 90%
“…Kang-Ai injection is an herbal medicine approved in 2002 by the China Food and Drug Administration (China FDA). It consists of Astragali Radix (Huangqi), Ginseng Radix et Rhizoma (Renshen) and kushenin (Kushensu), and is indicated for many cancers, leukopenia and chronic hepatitis B [6][7][8]. Previously, we have nished the chemical identi cation and content determination of the main alkaloids (oxymatrine, matrine), astragalosides (astragaloside IV) and ginseng saponins (ginsenosides Rg1, Re) in Kang-Ai injection [9].…”
Background: Kang-Ai injection is widely used as an adjuvant therapy drug for many cancers, leukopenia, and chronic hepatitis B. Circulating alkaloids and saponins are believed to be responsible for therapeutic effects. However, their pharmacokinetics (PK) and excretion in vivo and the risk of drug-drug interactions (DDI) through inhibiting human cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes remain unclear. Methods: PK and excretion of circulating compounds were investigated in rats using a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS) method. Further, the inhibitory effects of nine major compounds against eleven CYP and UGT isozymes were assayed using well-accepted specific substrate for each enzyme. Results: After dosing, 9 alkaloids were found with Cmax and t1/2 values of 0.17-422.70 μmol/L and 1.78-4.33 h, respectively. Additionally, 28 saponins exhibited considerable systemic exposure with t1/2 values of 0.63-7.22 h, whereas other trace saponins could be negligible or undetected. Besides, over 90% of alkaloids were excreted through hepatobiliary and renal excretion. Likewise, astragalosides and protopanaxatriol (PPT) type ginsenosides also involved in hepatobiliary and/or renal excretion. Protopanaxadiol (PPD) type ginsenosides were mainly excreted to urine. Furthermore, PPD-type ginsenosides were extensively bound (fu-plasma approximately 1%), whereas astragalosides and PPT-type ginsenosides displayed fu-plasma values of 12.35% and 60.23-87.36%, respectively. Moreover, matrine, oxymatrine, astragaloside IV, ginsenoside Rg1, ginsenoside Re, ginsenoside Rd, ginsenoside Rc, and ginsenoside Rb1 exhibited no inhibition or weak inhibition against several common CYP and UGT enzymes IC50 values between 8.81 and 92.21 μM. Through kinetic modeling, their inhibition mechanisms towards those CYP and UGT isozymes were explored with obtained Ki values. In vitro-in vivo extrapolation showed the inhibition of systemic clearance for CYP or UGT substrates seemed impossible due to [I]/Ki no more than 0.1.Conclusions: We summarized the PK behaviors, excretion characteristics and protein binding rates of circulating alkaloids, astragalosides and ginsenosides after intravenous Kang-Ai injection. Furthermore, weak inhibition or no inhibition towards these CYP and UGT activities could not trigger harmful DDI when Kang-Ai injection is co-administered with clinical drugs primarily cleared by these CYP or UGT isozymes.
“…TACE is not, however, ideal as a long-term cure since it often reduces immunity, aggravates the impairment of liver function and reduces life quality of HCC patients [27]. Finding a way to reduce liver injury and improve clinical e cacy and quality of life has thus become a key issue and many patients in Asia are seeking help from traditional herbal medicines [28][29].…”
Background: Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC.Methods: Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results: Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. Conclusions: Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.
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