Professor Zijun Liao: Clinical practice has proven that recombinant human endostatin is effective and safe in the treatment of malignant serous effusion

*It is only for medical professionals to read for reference.
What should I do with lung cancer patients with malignant serous effusion? Clinical experts give an effective response plan! Malignant serous effusion refers to the effusion caused by a variety of malignant tumors involving the thoracic cavity, abdominal cavity and pericardial cavity and its serous membrane.
It is a common complication of malignant tumors, most commonly in lung cancer [1].

The appearance of malignant serous effusion often indicates that the primary tumor has metastasized locally or spread throughout the body, treatment is difficult, and the prognosis is poor [1].

So, how to deal with malignant serous effusion in patients with lung cancer clinically? The "medical community" has the honor to invite Professor Liao Zijun from Shaanxi Cancer Hospital to share his experience in the diagnosis and treatment of lung cancer with malignant pleural and ascites.

Lung cancer with high incidence of pleural effusion, poor prognosis and low quality of life Malignant serous effusion is very common clinically, usually divided into malignant pleural effusion, malignant ascites and malignant pericardial effusion [1].

Professor Liao Zijun pointed out that “20%~25% of patients who are newly diagnosed with lung cancer in clinical practice are early stage, 70%~75% are middle-advanced stage, malignant serous effusion is a common comorbidity of middle-advanced stage lung cancer.

Lung cancer mainly causes Pleural effusion, followed by pericardial effusion, and abdominal effusion is rare.

About 15% of patients newly diagnosed with lung cancer have pleural effusion, and in the development of lung cancer, 50% of patients will eventually have pleural effusion.
.

"the combined incidence of malignant pleural effusion of lung cancer is so high, its patients what harm? Professor Liao Zijun said, “The occurrence of pleural effusion indicates that lung cancer has advanced to advanced stages, and the life expectancy of patients will be significantly shortened.

Without targeted drug treatment, the survival time of advanced lung cancer rarely exceeds one year; after combined pleural effusion, Even through active treatment, the patient's survival period is less than one year, and most patients' survival period is 3 to 6 months.

" "Lung cancer with pleural effusion not only affects the survival of the patient, but also affects the quality of life of the patient.

"Professor Liao Zijun further pointed out, "First of all, a large amount of pleural effusion will cause the patient to have difficulty breathing and restless sitting or lying down.

In addition, the patient's nutritional loss is very serious.

Each 100mL of malignant serous effusion contains 4g of protein.
According to our clinical observations, patients can produce 500~1000mL of pleural fluid every day.
If 1000mL of pleural fluid is drained every day, the patient will lose up to 40g of protein.

At the same time, pleural effusion will also adversely affect other anti-tumor treatments.

"Drainage by catheter + drug perfusion based on recombinant human endostatin can effectively treat malignant pleural effusion and malignant serous cavity effusion.
If lung cancer patients develop pleural effusion, they need to be actively treated in the thoracic cavity.

Local puncture Tube drainage can alleviate the patient’s chest tightness and shortness of breath.

How to operate clinically? Professor Liao Zijun explained, “First of all, locate under the guidance of B-ultrasound.
After positioning, puncture, place the tube, and pump water.
The amount of water pumped and the pumping speed mainly depend on The patient's feelings, age, whether there are any underlying diseases, physical fitness, the color of the effusion, etc.

For patients with good physical condition and a large amount of light yellow pleural effusion, the maximum can be pumped up to 2000mL; for older patients with blood pleural effusion with underlying diseases, we generally pump 500~600mL or 700~800mL.

In addition, the systemic nutritional support treatment should be given at the same time as the fluid is drawn.

At the beginning of the catheterization and drainage, we will draw 100~300mL of effusion for exfoliative cytology.

If the exfoliative cytology is positive, the patient will be perfused with intrathoracic drugs.
Cytotoxic drugs (cisplatin and nedaplatin commonly used in clinical practice) or biological agents can be perfused.

If multiple examinations of exfoliation cytology are negative, but there is a histopathological diagnosis of the primary tumor, and pleural effusion caused by infection (such as tuberculosis), cardiac insufficiency, and cirrhosis of the liver is excluded, we can also follow the malignant serosal cavity Liquid to deal with.

"However, only local puncture and drainage can not cure the symptoms, but it is necessary to fundamentally reduce the formation of effusion.

The formation mechanism of malignant serous effusion is very complicated and has not been fully elucidated.

At present, many scholars believe that malignant tumors release pro-inflammatory factors, including immunoregulatory factors and factors that induce increased vascular permeability, such as vascular endothelial growth factor (VEGF), etc.
, which can cause capillary regeneration and fluid leakage caused by increased permeability The increase may be the main mechanism of malignant serous effusion [1].

How to prescribe the right medicine? Professor Liao Zijun pointed out, “When choosing drugs, we must first target the tumor itself, and secondly target the target of VEGF.
Recombinant human endostatin (trade name "Endo") is the main clinical drug of choice.

Recombinant human vascular endothelial inhibition It has been applied for nearly 20 years since the Phase III clinical study, and we have accumulated a wealth of clinical experience.

Its side effects are very low, and there are no obvious gastrointestinal reactions, liver and kidney damage, and bone marrow suppression.
It is a very safe product.
Drugs.

If the standard of no longer producing pleural effusion for three months is the standard, 80% of patients can achieve this effect after treatment, and the quality of life of the patients has also been significantly improved.

"Evidence-based support + consensus recommendation, recombinant human endostatin treatment of malignant Serosal effusion is likely to be endostatin, which is the endogenous factor with the strongest inhibitory effect on angiogenesis found so far [1].

A number of studies have shown that recombinant human endostatin has extensive inhibitory and regulatory functions on the VEGF family, and has excellent anti-vascular and anti-lymphangiogenesis effects, which can reshape the vascular structure of tumors and make them normal.
Reduce the generation of leakage and serous effusion [2-4].

In recent years, relevant clinical studies have shown that recombinant human endostatin has achieved good results in the treatment of malignant pleural effusions.

The results of a prospective, randomized controlled, national multi-center phase III clinical study of the intracavitary application of recombinant human endostatin and/or cisplatin in the treatment of malignant pleural effusions showed that [5], recombinant human endostatin alone The objective response rate (ORR) of the drug was equivalent to that of cisplatin alone (48.
51% vs.
46.
39%, P>0.
05), and the combination of two drugs significantly improved the ORR (63%, P=0.
0189) compared with the single drug; subgroup analysis showed that, Recombinant human endostatin is more effective for bloody effusions, that is, the ORR of recombinant human endostatin single drug is significantly better than that of cisplatin single drug (recombinant human endostatin group 71.
05%, combination group 80.
00%, cisplatin Group 45.
16%, P=0.
0090).

In terms of safety, the safety of recombinant human endostatin is good.
The incidence of adverse events (AE) when used alone is significantly lower than that of cisplatin (P=0.
0005), and the incidence of AE when combined with cisplatin is similar to that when used alone.
Cisplatin is similar (P=0.
2866).

Based on the results of this study, the "Chinese Expert Consensus on Anti-angiogenic Drug Therapy for Advanced Non-small Cell Lung Cancer (2020 Edition)" recommends that patients with advanced non-squamous non-small cell lung cancer with malignant pleural effusion can be treated on the basis of systemic therapy Topical use of bevacizumab or recombinant human endostatin.

In this regard, Professor Liao Zijun said from the perspective of clinical use, "We have more than ten years of clinical experience in the use of recombinant human endostatin combined with cytotoxic drugs/interleukins as a common perfusion regimen, and more than 500 cases of pleural effusions.
In the
past, the price of recombinant human endostatin was relatively high, but now its price has been greatly reduced.
More patients can afford it, and it is more convenient for us to use it in clinical practice.
.

"Finally, Professor Liaozai Jun told the" medical profession ", currently recombinant human endostatin there are some issues worthy of further exploration of the clinical use of hormone:" first, we present the maximum dose to the patient in the clinic is 90mg / times ( Thoracic cavity) or 120mg/time (abdominal cavity), and no obvious side effects were observed.

So when is the amount of recombinant human endostatin used for the best effect? At what dose does the patient have obvious side effects and cannot tolerate it? Secondly, the efficacy of recombinant human endostatin as a single agent is not as good as that of combination drugs, so with which drugs and what kind of combination is the best solution? Third, the current positive report rate of serous effusion exfoliation cytology is 30%-40%, and most of them may be positive after two or three tests, and even more than a dozen times before they can be found.
Tumor cells.

How to improve the positive test rate of exfoliated cytology of serous effusion? These are issues that need to be explored by pharmaceutical companies and clinical cooperation.

inhibits lymphangiogenesis and lymphatic metastasis of Lewis lung carcinoma xenograft in mice [J].
Thorac Cardiovasc Surg.
2011;59(3):133-136.
[4]Jia Y, Liu M, Huang W, et al.
Recombinant human endostatin endostar inhibits tumor growth and metastasis in a mouse xenograft model of colon cancer [J].
Pathol Oncol Res.
2012;18(2):315-323.
[5] Qin Shukui, Yang Liuqing, Liang Jun, et al.
A prospective, randomized controlled, national multi-center phase III clinical study of intracavitary use of recombinant human endostatin and/or cisplatin in the treatment of malignant pleural effusions[J].
Journal of Clinical Oncology.
2017; 22(3): 193-202.