Systemic Therapy for Hepatocellular Carcinoma: Chinese Consensus-Based Interdisciplinary Expert Statements.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and causes many cancer-related deaths worldwide; in China, it is the second most prevalent cause of cancer deaths. Most patients are diagnosed clinically with advanced stage disease. Summary: For more than a decade, sorafenib, a small-molecular-weight tyrosine kinase inhibitor (SMW-TKI) was the only molecular targeted drug available with a survival benefit for the treatment of advanced HCC. With the development of novel TKIs and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, though angiogenic-based targeted therapy remains the backbone for the systemic treatment of HCC, to date, no Chinese guidelines for novel molecular targeted therapies to treat advanced HCC have been established. Our interdisciplinary panel on the treatment of advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, pathologists, orthopedic surgeons, traditional Chinese medicine physicians, and interventional radiologists has reviewed the literature in order to develop updated treatment regimens. Key Messages: Panel consensus statements for the appropriate use of new molecular -targeted drugs including doses, combination therapies, adverse reaction management as well as efficacy evaluation, and predictions for treatment of advanced HCC with evidence levels based on published data are presented, thereby providing an overview of molecular targeted therapies for healthcare professionals.

Low-Frequency Sonophoresis of Chinese Medicine Formula Improves Efficacy of Malignant Pleural Effusion Treatment.

OBJECTIVE: To evaluate whether low-frequency ultrasound-facilitated transdermal delivery of a Chinese medicine (CM) formula could improve the efficacy of intrapleural administration of interleukin-2 (IL-2) in treatment of malignant pleural effusion (MPE). METHODS: A total of 110 eligible participants were randomized into the low-frequency sonophoresis (LFS) of CM (LSF/CM) group (55 cases) and the control group (55 cases) by simple randomization using a random number table. The control group was treated with an intrapleural administration of IL-2; and the LFS/CM group was treated with LFS of a CM gel formulation, combined with the same IL-2 injection as in the control group. The CM formula consisted of Semen Lepidii, Semen Sinapis, Ramulus Cinnamomi, Poriacocos, Herba Lycopi, and Radix Paeoniae Rubra. After 2-week treatment, the therapeutic outcome was determined by the change of the amount of MPE, which was evaluated by B-scan ultrasound and/or chest X-ray, and the change of quality of life (QOL) scores, which were evaluated by the Eastern Cooperative Oncology Group (ECOG) performance status. RESULTS: A significantly higher objective remission rate (ORR) was obtained with intrapleural IL-2 plus LFS/CM than IL-2 treatment alone (P=0.049). In addition, more patients in the LFS/CM group than in the control group had an improved QOL score (P=0.048), and no patients in the LFS/CM group had a reduced QOL. CONCLUSION: LFS of CM formulation could effectively alleviate MPE and improve the QOL of cancer patients.

Topical Delivery of Modified Da-Cheng-Qi Decoction () Using Low-Frequency Ultrasound Sonophoresis for Refractory Metastatic Malignant Bowel Obstruction: An Open-Label Single-Arm Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of topical delivery of modified Da-Cheng- Qi Decoction (, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design. METHODS: Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcome was the remission of intestinal obstruction, and improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators. RESULTS: Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, are as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal function or blood coagulation were observed. CONCLUSION: Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.

Efficacy of Topical Compound Danxiong Granules for Treatment of Dermatologic Toxicities Induced by Targeted Anticancer Therapy: A Randomized, Double-Blind, Placebo-Controlled Trial.

Dermatologic toxicities resulting in dose reduction or discontinuation of treatment pose challenges for targeted anticancer therapies. We conducted this randomized, double-blind, placebo-controlled trial to investigate the efficacy of topical application of Compound Danxiong Granules (CDG) for treatment of dermatologic toxicities associated with targeted anticancer therapies. One hundred and ten patients with dermatologic toxicities induced by targeted anticancer therapies were randomly assigned to CDG or placebo group. Each crude herb (Rhizoma Chuanxiong, Paeonia suffruticosa Andr., Cortex Phellodendri, Geranium sibiricum L., and Flos Carthami) was prepared as an instant herbal powder. Application of the CDG via topical washes lasted 20 minutes, twice daily, for 10 days. The primary outcome was the total effective rate, defined as reduction in at least one grade of skin toxicity. The total effective rate was 77.61% (52/67) in the CDG group and 27.27% (9/33) in the placebo group (P < 0.0001). Compared to the placebo treatment, CDG treatment achieved a higher total effective rate for hand-foot skin reaction (95.45% versus 27.27%), acneiform eruption (69.23% versus 30.78%), and paronychia (68.42% versus 22.22%). Topical application of CDG can effectively attenuate dermatologic toxicities induced by targeted anticancer therapies. The effect of CDG was more pronounced in hand-foot skin reaction.

[Effect of qianjin huanglian pill on kidney in insulin resistance mice].

OBJECTIVE: To investigate the effect of qianjin huanglian pill on kidney in monosodium L-glutamate (MSG)-treated insulin resistance (IR) mice. METHOD: The ameliorative effect of qianjin huanglian pill on IR in MSG mice was evaluated in comparison with rosiglitazone (Ros). The fasting serum glucose, fasting serum insulin, insulin sensitivity index, urinary albumin excretion, glomerular diameter and pathological changes of kidney were investigated in the evaluation. RESULT: After 2 weeks of qianjin huanglian pill treatment, the urinary albumin excretion (UAE) was reduced in low-dose group (P < 0.05) as compared with the model group. After 4 weeks of qianjin huanglian pill treatment, the fasting serum glucose was reduced in high-dose group (P < 0.001 compared with the model group). ISI of mice was ameliorated in high-dose group (P < 0.05 compared with the model group). The glomerular diameter was decreased, the hyperplasia of glomerulus was ameliorated in high-dose and low-dose groups (P < 0.01 compared with model group). CONCLUSION: In MSG mice, we found qianjin huanglian pill could increase insulin sensitivity, decrease the urinary albumin excretion, ameliorate the pathological changes of kidney due to insulin resistance.

[Influence of modified qianjin huanglian pill on pancreas of mice with insulin resistance].

OBJECTIVE: To investigate the influence of modified Qianjin Huanglian Pill (QJHL), a Chinese herbal compound, on pancreas in mice with monosodium L-glutamate (MSG) induced insulin resistance (IR) and its molecular mechanism. METHODS: Controlled by rosiglitazone (Ros), the MSG indiced IR mice were treated with QJHL for 28 days. The laboratory indices were examined including fasting serum glucose (FSG), fasting serum insulin (FSI), insulin sensitivity index (ISI), and morphological changes of pancreas, and levels of insulin receptor (InsR), insulin receptor substrate (IRS1/2) and glucose transporter (GLUT2) mRNA expression in pancreas tissue were determined by the reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: As compared with the model group, the level of FSG was lower (P < 0.01) and ISI was higher (P < 0.05) after treatment in the QJHL treated group, with pancreatic islet hyperplasia and hypertrophy ameliorated significantly (P < 0.01). And these changes were similar to those in the Ros treated group (P > 0.05). Moreover, the level of GLUT2 mRNA expression in pancreas of the QJHL group increased significantly (P < 0.01), while it was unchanged in the Ros group. CONCLUSION: QJHL could reduce IR, ameliorate pathological changes of pancreas, which is possibly related with its action on increasing GLUT2 mRNA expression in the pancreas tissue.