Professor YANG Yu-fei's Experience on the Integrated Chinese and Western Medicine Treatment Strategy for Advanced Colorectal Cancer

JIANG Hai-jun (江海軍), He Bin (何 斌), ZHANG Tong (張 彤), YANG Yu-fei (楊宇飛)

1. Beijing University of Chinese Medicine, Beijing, 100029, China

2. Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China

ABSTRACTColorectal cancer is one of the common malignant tumors in China. It poses a serious threat to the national health of China. For advanced colorectal cancer, the main goal of treatment is to prolong survival and improve quality of life. It complements other advantages, showing good therapeutic results. However, how to grasp the timing of integrated Chinese and Western Medicine for the treatment of advanced colorectal cancer and use the integrated Chinese and Western Medicine treatment methods flexibly contains profound therapeutic art. Prof. YANG Yu-fei is an authoritative expert in the field of integrated Chinese and Western medicine for colorectal cancer. She is good at accurately grasping the timing of treatment of integrated Chinese and Western Medicine, and flexibly adjusts the treatment strategy according to the specific conditions. In this paper, we shared Professor YANG Yu-fei's strategy for treating advanced colorectal cancer with emphasis on integrated Chinese and Western Medicine and attached a typical case, with a view to provide reference for the treatment of advanced colorectal cancer with integrated Chinese and Western Medicine.

KEYWORDS Integrated Chinese and western medicine; Advanced colorectal cancer; Treatment timing art

Colorectal cancer is one of the common malignant tumors of the digestive tract. Its incidence rate is the third in malignant tumors in China, and the mortality rate ranks fifth[1]. Advanced colorectal cancer accounts for more than 50% of all colorectal cancers, and the 5-year survival rate is about 8.1%[2].Most patients cannot be cured. The main goal of treatment is to prolong survival and improve quality of life, and the treatment by Western medicine has becomes tandard one, two, and three line treatment schemes[3]. And the FOLFOX and FOLFIRI schemes have established first and second line treatment status, based on genotyping, primary site, combined with bevacizumab or cetuximab. In the treatment of regregni or furazolinib, the third-line treatment is recommended. A continuous collection of 77,490 cases of advanced colorectal cancer in the US SEER database from 1988 to 2008 showed that the median survival of real world advanced colorectal cancer was up to 14 months[4]. A multi-center crosssectional survey of 37 tertiary hospitals in China shows that from 2012 to 2014, the direct expenditure for diagnosis and treatment of colorectal cancer patients in China was 67,408 yuan per case, and 75.0% of families could not afford it[5]. Traditional Chinese medicine for the treatment of malignant tumors has positive effects, low price and high accessibility. A large number of clinical studies[6,7]confirmed that the combination of Chinese and Western medicine for the treatment of advanced colorectal cancer can alleviate the adverse reactions of patients, improve the quality of life of patients,and prolong survival. Therefore, the combination of Chinese and Western medicine treatment has become an important means of treatment for advanced colorectal cancer. A special scientific research project of capital health development led by Professor YANG Yu-fei[8]included 120 patients with advanced colorectal cancer. The combination of Chinese and Western medicine treatment were used. The average survival time of stage IV was 24 months, and the median survival time was 21 months.Satisfactory results were achieved. In the treatment of advanced colorectal cancer, the control of the timing of the treatment of integrated Chinese and Western medicine contains profound therapeutic art. Professor YANG YU-fei is a doctoral tutor in Xiyuan Hospital of China Academy of Chinese Medical Sciences,chief researcher of China Academy of Chinese Medical Sciences, and a Qi Huang Scholar of National Administration of Traditional Chinese Medicine and national leader in colorectal cancer in clinical and scientific research. She is rigorous in academic research and has rich experience in the treatment of advanced colorectal cancer by the combination of traditional Chinese medicine and Western medicine. And she formed a systematic treatment plan for advanced colorectal cancer with integrated Chinese and Western Medicine[9].I have the privilege as her master student to learn her experience for treating patients and I would like to summarize those as follows.

CONTROL THE TIMING OF TREATMENT

Professor YANG Yu-fei is good at grasping the timing of treatment and controlling the initiative of treatment. According to the condition of the diseases, she provides individualized treatment plans for patients, with pure Chinese medicine treatment, or integrated Chinese and Western medicine treatment, or Western medicine treatment supplemented by traditional Chinese medicine treatment.

Different Stages of Disease in Different Patients

For patients with advanced diagnosed colorectal cancer at the initial diagnosis, it is judged whether there is a chance of radical surgery,and actively seek for the possibility of conversion treatment; If there is no opportunity for radical cure,according to the patient's age, physical condition,economic conditions and other factors, Chinese medicine treatment, both integrated Chinese and Western Medicine treatment, were chosen, with western medicine as the main Chinese medicine supplementary treatment; if the patient comes to the clinic during chemotherapy, Chinese medicine will be actively correcting at this stage, which is three-step music in two stages[10]. The first step is the first week of chemotherapy for invigorating the spleen and stomach, using Liujun Anwei Decoction(六君安胃湯) to protect middle Jiao, spleen and stomach, the source of life, and to alleviate the adverse reactions of the digestive tract. The second step is to invigorate spleen and supplement kidney stage in the second and third week of chemotherapy. Using Qitu Erzhi Decoction (芪菟二至湯) to regulate and supplement the source of life,and to prevent marrow control. The third step is to use the method of resolving superficies syndrome with pungent and cool natured drugs, clearing heat and removing toxic to treat exogenous and heat disease. If seeing a patient is in the maintenance phase after chemotherapy, you may consider choosing either pure Chinese medicine or Chinese medicine assisted by sufficient amount of Xeloda/Tiggio or Chinese medicine combined with lowdose oral targeted drug and tigeotine/Xeloda. If the patient is in the anti-angiogenic targeted therapy with furazolinib or regregni. At this stage, Chinese medicine relies on strengthening the righteousness and eliminating evils to reduce the side effects of targeted drugs.

Different Periods of Disease in the Same Patient

For the different periods of treatment of the same patients, we should be focused on different treatment schemes. If the tumor progresses rapidly with compression symptoms, the priority is to choose Western medicine as the main treatment assisted by Chinese medicine treatment, that is, to actively accept Western standard chemotherapy.TCM actively supports at this stage to alleviate the adverse reactions of chemotherapy, or local treatments (such as radiotherapy) to reduce tumor burden. After the completion of Western standard chemotherapy, the tumor is relatively stable. Give traditional Chinese medicine or traditional Chinese medicine combined with oral chemotherapeutic drug ± oral targeted drug maintenance therapy; if the tumor progresses slowly and has no symptoms of oppression, consider administering traditional Chinese medicine or traditional Chinese medicine combined with oral chemotherapeutic drug ± oral targeted drug therapy. Generally, try pure Chinese medicine treatment first. If the condition is stable and continue to be treated purely by Chinese medicine,if the effect of pure Chinese medicine treatment is not satisfactory, consider giving Chinese Medicine decoction of stengthening vital qi and dispelling pathogenic qi, combined with sufficient amount of Xeloda/Tiggio, if necessary, add 1-2 kinds of anti-cancer proprietary Chinese medicines, if The condition is still uncontrollable, and the Chinese medicine can be combined with the low-dose apatinib and Xeloda/Tiggio in combination with the patient's willingness to treat. If the disease is still not effectively controlled during the treatment,comprehensive consideration of the condition and combined with the patient's willingness to treat,consider strengthening the power of Chinese medicine to fight cancer.

Distinguish the Relationship Between Vital and Pathogenic Qi in Chinese medicine

Professor YANG Yu-fei thinks that the core pathogenesis of colorectal cancer[11]is "deficiency of origin and excess", deficiency of spleen is the initiating factor, stagnation of liver is the promoting factor, deficiency of spleen, liver and kidney is the key factor at the end stage; Phlegm toxin, dampness toxin and blood stasis toxin are the signs of the disease, and the specimens are causality to each other. Therefore, in the treatment, we should keep the pathogenesis of the disease, strengthen the vital energy and remove pathogens at the same time, but mainly strengthen the vital energy and strengthen the spleen, and then nourish the liver and kidney,and treat the pathogens flexibly according to the severity of phlegm, dampness and blood stasis. In clinical application, we should pay attention to the visceral differentiation. Sijunzi Decoction (四君子湯), Xiaojianzhong Decoction (小建中湯), Liujunzi Decoction (六君子湯), Sishen Pills (四神丸), Erzhi Pills (二至丸), etc. were used. Chinese patent medicines often use Huachansu Tablets (華蟾素片),Antico Capsules (安替可膠囊), Compound Canthari Capsules (復(fù)方斑螯膠囊), and Pingxiao Capsules(平消膠囊) etc..

"Basic Questions Yuan Zheng Ji Da Lun"said: Professor Yang Yu-fei stresses that the process of treatment of advanced colorectal cancer is a protracted battle. In pure Chinese medicine,attention should be paid to attacking the evil, not to quick success and quick profit, and not to throwing in large quantities of attacking and cutting products in pursuit of a rapid reduction of the tumor, so as to avoid damaging the health of the patient, which is counter-productive. While eliminating evil, we should pay attention to the cultivation of healthy qi and follow the concept of "the organic combination of protecting healthy qi and attacking cancer to eliminate evil"[12]. At the same time, it is pointed out that the traditional Chinese medicine treatment is quite different from the western medicine which advocates killing tumor cells to the maximum extent, and advocates "survival with tumor". If the patient's healthy qi is vigorous, the ratio of Chinese medicine decoction to reinforce healthy qi and dispel pathogen is about 6:4, and 1-2 anti-cancer proprietary Chinese patent medicines are added as needed; If the patient is sufficient in healthy qi, the ratio of Chinese medicine decoction for reinforcing healthy qi and dispel pathogen is 7:3 or 8:2, and 1 kind of anti-cancer Chinese patent medicine is added according to the need; if the healthy qi is weak, the Chinese medicine decoction will actively support the righteousness and avoid excessive attack.

During the treatment, the tumor markers were checked every month, and the imaging examination was performed every 2 months to evaluate the curative effect, which includes tumor-related main symptoms,the tumor markers, and the size of the tumour etc. The evaluation system included the western medical RECIST evaluation criteria, which not only focused on the size of the tumor, but also emphasized people-oriented. It paid attention to the quality of life of patients, but also highlighted the characteristics of Chinese medicine.

PROVED CASES

LUO, female, 35 years old, Case No.: 5574084.The patient 2014-05 line had rectal cancer analectal radical surgery, and the pathological suggestion was IIIb period. From 2014-06 to 2014-09 the patient had 4 cycles FOLFOX regimen chemotherapy.It was found in October 2014 liver transfer occurred, and "XELIRI" regimen for 4 cycles of chemotherapy was implemented, Meanwhile after 25 times of pelvic radiotherapy, liver lesions disappeared. Lung metastasis was found in 2015-08. The surgeon evaluated the inability to perform the surgery, and performed 4 cycles of XELIRI chemotherapy from August 2015 to October 2015 to evaluate the stability of the disease. The patient had 2 children, and has no job. His husband worked, and his economic conditions were not good.Treatment costs were about 20,000 yuan per year for him. Therefore, chemotherapy is not combined with targeted drugs and he cannot afford to continue the treatment. She decided to give up her treatment,when she was introduced by someone to Professor YANG for the treatment.

First diagnosis: 2015-10-29, symptom: lack of strength level 6, abnormality, poor sleep, difficulty falling asleep；stool is not formed; cacation is not clean, 3-4 times a day, dry mouth, bitter mouth, short temper, tongue bland, red coating, white teeth, thin pulse strings, KPS 60. The patient's left half intestine was all wild type. The short-term goal of treatment is to improve symptoms and control tumor progression. The long-term goal of treatment was to extend the effective survival time and strive for the survival time of stage IV to exceed 30 months. Patients cannot afford the cost of continuing Western medicine chemotherapy due to financial reasons, and thus can be treated with Chinese medicine first. The 4 clinics were combined, and the dialectic was the liver and spleen and the syndrome. Prescription: Radix Bupleuri(Chai Hu) 6 g, Radix Astragali (Sheng Huang Qi)15 g, Radix Codonopsis (Dang Shen) 10 g, dryfried Rhizoma Atractylodis Macrocephalae (Chao Bai Zhu) 10 g, Fu Shen 10 g, Radix et Rhizoma Glycyrrhizae Praeparata cum Melle (Zhi Gan Cao) 6 g, Radix Asparagi (Tian Dong) 10 g, Radix Ophiopogonis (Mai Dong) 10 g, Radix Adenophorae(Nan Sha Shen) 10 g, Radix Glehniae (Bei Sha Shen) 10 g, Fructus Ligustri Lucidi (Nv Zhen Zi)10 g, Herba Ecliptae (Han Lian Cao)10 g, Ramulus Euonymi (Gui Jian Yu) 15 g, Radix Rhapontici(Lou Lu) 15 g, Herba Scutellariae Barbatae (Ban Zhi Lian) 15 g, Nan Fang Dou Shan 6 g, Radix Scutellariae (Huang Qi) 6 g; Chinese patent medicine Weimaining Capsule (威麥寧膠囊) 3, bid;Huachansu Tablets (華蟾素片) 3, bid. Patients were encouraged to build confidence in overcoming the disease, and instructed to check the tumors every month, to check the lung CT plain scan every 2 months, and to have further consultation them every 1-2 months.

After repeated visits, the symptoms of fatigue and anorexia gradually reduced, physical strength gradually recovered, and treatment confidence gradually increased. In June 2016, the patient consciously controlled the disease and stopped taking Chinese medicine on his own. The metastasis of the posterior lung increased rapidly. In August 2016, she received a gamma knife treatment for lung lesions. After that, She continued to receive Chinese medicine treatment. The Chinese medicine decoction used the method of strengthening the spleen and replenishing kidney. The Chinese patent medicine used Huachansu Tablets (華蟾素片),Antico Capsules (安替膠囊), Compound Canthari Capsules (復(fù)方斑螯膠囊), and Pingxiao Capsules(平消膠囊), etc., adjusting them once every 2-4 months, and monitoring the liver renal function. The lung lesions were stable.

2017-10-12 Further consultation,2017-09-25 check CEA 25 ng/ml, higher than before, 08-07 lung CT showed right lung metastasis 4.7＊3.3 cm, increased earlier, considering the progress of the disease, symptom manifestations:fatigue, no pleasure in eating, the stool is formed 2-3 times a day, exhausting more, sleeping poorly,dreaming, irritable. The tongue is thin. The tongue coating of the tongue tip is slightly red and yellow.The pulse string is weak, and the syndromes are liver stasis, spleen deficiency, dampness, heat, and internal resistance. The patient's disease progress was treated with Chinese medicine combined with capecitabine. The prescription: capecitabine 1.5 g,bid. Rhizoma Pinelliae Praeparatum (Jiang Ban Xia)10 g, Pericarpium Citri Reticulatae (Chen Pi) 10 g,raw Radix Astragali (Sheng Huang Qi) 15g, Radix Codonopsis (Dang Shen) 10g, Poria (Fu Ling)10 g,fried Rhizoma Atractylodis Macrocephalae (Chao Bai zhu) 10 g, Radix et Rhizoma Glycyrrhizae Praeparata cum Melle (Zhi Gan Cao) 6 g, Semen Ziziphi Spinosae (Suan Zao Ren) 15 g, Radix Bupleuri (Chai Hu) 10 g, Fructus Ligustri Lucidi(Nv Zhen Zi) 10 g, Herba Ecliptae (Han Lian Cao)10 g, Fructus Psoraleae (Bu Gu Zhi)10 g, Semen Cuscutae Dodder (Tu Si Zi) 10 g, Radix Paeoniae Rubra (Chi Shao) 10 g, Rhizoma Chuanxiong(Chuan Xiong) 10 g, Colla Corii Asini Pilula (E Jiao Zhu) 10 g.

2017-12-18 further consultation, CEA continues to increase, lung lesions continue to increase,considering the progress of the disease, the symptoms: morning cough, hemoptysis, no appetite,profuse dreaming, stool formation 2-3 times, short temper. Chinese medicine combined with lowdose apatinib and tigio were given. Prescription:tigio 20 mg, bid, sustained; apatinib 250 mg, qd,sustained; Chinese medicine prescription was Liujunzi Decoction (六君子湯) and Erzhi Pills (二至丸) plus Herba Agrimoniae (Xian He Cao), Rhizoma Phragmitis (Lu Gen), Rhizoma Imperatae (Bai Mao Gen), Miao San Xian.

2018-01-11, further consultation, she had a hemoptysis, and the CEA was 6.4 ng / ml lower than before. The lung lesion was 4.0 3.5cm. The effect was stable, followed by Chinese medicine combined with tigio and apatinib. As the patient enjoyed part of the donated drug discount, the monthly treatment cost of this program was less than 2,000 yuan, and the patient was glad to accept it. The patients were re-examined every 2-3 months, and the results were evaluated based on tumor-related symptoms,CEA, and size of the lung lesions. The condition was stable, with longer asymptomatic / toxic survival time (TWIST). At each follow-up visit, the patient was asked to pay attention to regulating their emotions, to be encouraged to build confidence in defeating the disease, to be told to do their best, to give the patient the greatest support, and to form an anti-cancer synergy among doctors, patients and their families.

2019-07-04 further consultation, lung CT in June 2019: lung lesions 6.6 3.6 cm, evaluated as disease progression (PD), After careful inquiry,I learned that the patient started to do business early in the year, working hard, and her condition progressed. It was recommended that patients received the "Iriticon + Cetuximab" regimen. During this period, Chinese medicine assisted in alleviating the adverse effects of chemotherapy. Specifically,in the first week of chemotherapy, Liuju Anwei Decoction (六君安胃湯) was used to protect middle jiao, the spleen and stomach, the foundation of the later life, to reduce the adverse reaction of digestion. For the 2nd week of chemotherapy, Qitu Erzhi Decoction (芪菟二至湯) was used to replenish the congenital essence to prevent bone marrow suppression, and a cold prescription was prepared for emergency needs. After completing 6-8 cycles of chemotherapy, the patient continued to come to the clinic for treatment with both integrated Chinese and Western Medicine.

2019-11-25 After returning to the clinic, the patient could not afford the cost of continuing chemotherapy after completing 4 cycles of"irinotecan + cetuximab" treatment due to economic reasons. A CT scan of the lung in September 2019 revealed a lung lesion of 3.7 3.5 cm, which was evaluated for MR. No further CT scans were performed. During the chemotherapy period, the Chinese medicine was not taken according to the doctor's advice. Recently, as she did not take Chinese medicine according to the doctor's advice,symptoms of palpitation, shortness of breath, and cough appeared. Symptoms: palpitation, shortness of breath after coughing, occasional cough and sputum, no obvious weakness, appetitive, sleepy,and stool formation, 2-3 times a day, Nocturia 2-3 times, recent weight stable, 42 kg, KPS 80 points.The patient's survival time has far exceeded the goals set at the initial diagnosis. The long-term goal for the next stage of treatment is to be more than 2 years. The near-term goal is to control the tumor as much as possible and improve the quality of life. The treatment plan was "traditional Chinese Medicine +Apatinib + Tigio".

So far, the patient's stage IV survival period has reached 61 months, including 49 months of outpatient treatment of integrated Chinese and Western medicine treatment. During this period, the patient's quality of life was higher.

Illustration: For advanced colorectal cancer that cannot be radically resected, western medicine treats with comprehensive treatment with the combination of chemotherapy and targeted therapy.When the patient firstly visits the doctor, she is in the maintenance treatment after the completion of the standard chemotherapy of Western medicine. The patient is irritable, the liver qi is stagnation, and the spleen is indifferent. The tangible pathogens forms,the tumor is formed. After operation, radiotherapy and chemotherapy, the healthy qi is damaged.Lack of strength, poor appetite, and poor bowel movements are the symptoms of spleen deficiency.Therefore, Sijunzi Decoction (四君子湯) plus Radix Bupleuri (Chai Hu) are used to soothe the liver and nourish the spleen. Dry mouth and bitterness are the syndromes of yin thick fluids injury after radiotherapy, so Radix Asparagi (Tian Dong), Radix Ophiopogonis (Mai Dong), Radix Adenophorae(Nan Sha Shen), Radix Glehniae (Bei Sha Shen),are used to nourish yin and produce fluids.

Fructus Ligustri Lucidi (Nv Zhen Zi), and Herba Ecliptae (Han Lian Cao) are used to supplement the innate and the acquired. Ramulus Euonymi(Gui Jian Yu), Radix Rhapontici (Lou Lu), Herba Scutellariae Barbatae (Ban Zhi Lian), Nan Fang Hong Dou are used for and detoxification and anticancer with with Weimaining Capsules (威麥寧膠囊), Huachansu Tablets (華蟾素片) to enhance the power of detoxification and anti-cancer. Chinese medicine combined with capecitabine was given.After 2 months of treatment, the patient's condition still progressed, and the targeted drug apatinib was added. The Chinese medicines used were Liujunzi Decoction (六君子湯) plus Erzhi Pill (二至丸) to supplement both the spleen and kidney. The patient had obvious hemoptysis. Rhizoma Phragmitis(Lu Gen), Rhizoma Imperatae (Bai Mao Gen),Ophicalcitum (Xian He Cao), were added to stop bleeding. When the patient had further consultation,the hemoptysis was stopped, the lesion was stable,and the curative effects were remarkable. After 18 months of treatment with Chinese medicine combined with low-dose eptatinib and tegafur, the patient's condition was re-progressed. At present,the patient's stage IV survival period has reached 61 months, and at the same time, the quality of life of the patient has been significantly improved.After KPS 60 points at the initial consultation, the patient can do business independently and achieve the treatment goals set at the initial diagnosis.The entire treatment process fully demonstrates that Professor YANG Yu-fei is good at accurately grasping the timing of integrated Chinese and Western medicine. She flexibly, individually and rhythmically adjusts the treatment strategy according to the stage of the patient's condition,showing the superb integrated Chinese and Western medicine treatment art.

CONCLUSION

In recent years, with the deepening of the dialogue between Chinese and Western medicine,the combination of Chinese and Western medicine treatment has received more and more attention from doctors and patients, and has achieved good results. How to choose the best time for the combination of Chinese and Western medicine, and to maximize the respective advantages of integrated Chinese and Western medicine to obtain the best treatment effect at a small economic cost, is a problem that every Chinese and Western medical practitioner should consider. Professor Yang Yu-fei combined with her many years of clinical experience,based on the characteristics of integrated Chinese and Western medicine, guided by the specific conditions, accurately grasp the timing of treatment of integrated Chinese and Western medicine, and specify individualized treatment plans for patients,reflecting the superb treatment art. She has formed a systematic and comprehensive treatment ideas for advanced colorectal cancer and has provided a reference for the treatment of advanced colorectal cancer with both Chinese and Western medicine.