Chinese herbal medicine for advanced pancreatic cancer

TCM is a 3,000-year-old holistic system of medicine combining medicinal herbs, acupuncture, food therapy, massage, and therapeutic exercise for both treatment and prevention of diseases 1. It has its unique theories around concepts of aetiology, systems of diagnosis, and treatment, which are vital to its practice. The theories of TCM include Yin-Yang (e.g. positive and negative), the five elements (fire, earth, metal, water, and wood), Qi (vital energy) and blood, Zhang-Fu (five viscerae and six bowels), as well as channels and collaterals (Meridian doctrine) 2 3. Diseases are considered to result from internal causes as well as external causes, which are defined as disturbances e.g., the imbalance between Yin and Yang. Chinese medicines consist typically of complex prescriptions combining between four and 12 different herbal ingredients, including minerals or animal components. The combinations are based on special Chinese diagnostic patterns that involve inspection, listening, smelling, inquiry, and palpation. Herbs are used for correcting the imbalance of Yin and Yang in the body and maintaining kinetic balance under the movement of five elements. “Bianzheng Lunzhi” (the differentiation of symptom patterns and the prescription of formula of herbs) is the application of these theories.

Herbal therapy is the most commonly used part of TCM, and includes around 3,200 herbs. Herbs often used in cancer patients include Ginkgo biloba, Panax ginseng, Astragalus membranaceus. About 300 mineral and animal extracts and over 400 formulas are used 2. TCM herbal therapy is applied in three different ways, including individualised treatment (prescription of herbs on the basis of a TCM differentiation of the symptoms), use of fixed herbal formula (such as Chinese patented medicines), or the combined use of herbal medicine with conventional therapy. The composition of herbal preparations, dosage, and treatment duration vary.

Prevalence of use

Traditional Chinese herbal medicine has been used in China to manage the symptoms of patients with pancreatic cancer, such as jaundice, pain, and low appetite. There is no available data for the prevalence of herbal medicine use in pancreatic cancer patients. However, in China, it is not uncommon for patients with advanced pancreatic cancer to use herbal preparations and other TCM therapies.

Theory

In TCM, there is no equivalent diagnosis for pancreatic cancer, but the treatment intends to relieve the symptoms related to pancreatic cancer. Herbal treatment is designed to inhibit tumour growth and metastasis, stop pain and improve symptoms, reduce the adverse effects of chemotherapy and/or radiotherapy, enhance immunity, prevent relapse, increase survival, and improve quality of life.

According to TCM theory, practitioners prescribe herbal formulae according to the differentiation of symptoms of patients with pancreatic cancer 4. Therefore, the treatment varies from patient to patient and even at different stages of the disease.

Providers

TCM practitioners can either prescribe herbal formulae as decoctions, or prescribe commercially marketed herbal products such as Chinese patented medicines. Chinese patented medicines are manufactured mainly in China, while other neighbouring countries such as Japan, Korea, also produce herbal products.

Legal issues

In most European countries, herbal medicines are strictly regulated as dietary supplements. The European Directive on Traditional Herbal Medicinal Products allows herbal medicines to be registered as drugs if they have been used for 30 years (at least 15 years in EU countries and 15 years in non-EU countries). 5

Chinese herbal medicine has been claimed by TCM practitioners to be able to improve survival and relieve pain and symptoms in pancreatic cancer patients. Our searches in Chinese literature databases (until April 2009) identified 26 clinical studies on herbal therapy for pancreatic cancer, including 4 randomised controlled trials 6 7 8 9 , 2 non-randomized studies 10 11,and 20 case series or case reports 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31. There are no study reports on other TCM modalities such as dietary therapy, acupuncture, qigong, or massage available from the literature searches for this CAM summary.

Controlled clinical trials

There were six clinical trials including four randomized trials testing different herbal medicine with or without chemotherapy in patients with advanced stage of pancreatic cancer (Table 1). In general, the controlled clinical studies showed significant benefit from the combination of Chinese herbal medicine with chemotherapy in complete and/or partial remission, clinical pain relief, or longer survival. There was no solid evidence for a relative benefit of Chinese herbal medicine alone over chemotherapy. However, the risk of bias in these studies is high due to small sample sizes, and methodological flaws in terms of randomization and blinding (e.g. limited description of generation of allocation sequence and allocation concealment), intention-to-treat analysis, and attrition.

The first randomized clinical trial with three arms compared Chinese herbal medicine alone with Chinese herbal medicine and chemotherapy or with transcatheter arterial chemoembolization (TACE) in 63 patients with medium and advanced pancreatic cancer.6 In the CHM group (n=25) the median survival time was 3.5 months, survival rates for 0.5, 1, and 2 years were 12%, 8%, and 4%, respectively. In the CHM plus chemotherapy group (n=12), the median survival time was 5.25 months and survival rates for 0.5, 1, and 2 years were 41.7%, 25%, and 8.3%, respectively. In the TACE group (n=26), the median survival time was 4.25 months, survival rates for 0.5, 1, and 2 years 46.2%, 30.8%, and 7.7%, respectively.

The second randomized clinical trial (n=58) compared radio/chemo therapy plus CHM (Group A) with radio/chemotherapy alone (Group B) in patients with medium and advanced pancreatic cancer.7 For group A (n=30) complete remission was reported in 4 cases, partial remission in 16 cases, no change in 8 cases, progressive disease in 2 cases. The 1-year survival rate was 80% (24/30), 2-year survival rate 46.6% (14/30); abdominal pain relief was reported in 83.3% (25/30). Group B (n=28) had complete remission in 2 cases, partial remission in 13 cases, no change in 9 cases, progressive disease in 4 cases. The 1-year survival rate was 50% (14/28), 2-year survival rate: 21.4% (6/28); abdominal pain relief 57.1% (16/28).

The third randomized clinical trial of 43 patients with medium or advanced pancreatic cancer received either chemotherapy and Yanshu injections (Group 1) or chemotherapy alone (Group 2).8 In Group 1 (n=22) the Karnofsky scores increased >10 in 12 cases, increased or decreased ≤10 in 6 cases, decreased >10 in 4 cases. With regards to cancer pain, complete remission was seen in 36.4% (8/22), partial remission in 50% (11/22), no change in 13.6% (3/22). Quality of life improved in 50% (11/22), remained stable in 27.3% (6/22), and deteriorated in 22.7% (5/22). In the chemotherapy only group (Group 2, n=21) the Karnofsky scores increased >10 in 5 cases, increased or decreased ≤10 in 4 cases, decreased >10 in 12 cases. For cancer pain complete remission was seen in 19.1% (4/21), partial remission in 28.6% (6/21), no change in 52.4% (11/21). Quality of life improved in 14.3% (3/21), was stable in 23.8% (5/21), and deteriorated 61.9% (13/21);

The fourth randomized clinical trial of 82 patients of Shenqi Yiai Ye versus cytokine versus chemotherapy included both liver cancer and pancreatic cancer patients and the data for pancreatic cancer were not reported separately.9

A non-randomized controlled trial (n=37) compared Chinese herbal medicine plus chemotherapy (group 1) with chemotherapy alone (group 2) in patients with advanced pancreatic cancer. In group 1 (n=19) partial remission was reported in 3 cases, stable disease in 16 cases, clinical benefit response in 12 cases. Median survival was 14.3 months, survival rates at 1, 2, and 3 years were 47.4% (9/19), 31.6% (6/19), and 15.8% (3/19), respectively. Group 2 (n=18) partial remission 1 case, stable disease in 15 cases, progressive disease in 2 cases; clinical benefit response in 7 cases. Median survival times was 8.1 months, survival rates at 1, 2, and 3 years were 33.3% (6/18), 16.7% (3/18), and 5.6% (1/18), respectively.

Another non-randomized controlled clinical trial (n=60) compared Chinese herbal medicine alone with chemotherapy alone in patients with advanced pancreatic cancer.11 In the Chinese herbal medicine group (n=32) partial remission was observed in 0 cases, stable disease in 17 cases, progressive disease in 15 cases. Median survival was 6.07 months, survival rates for 3, 6, and 12 months: 65.6% (21/32), 50% (16/32), and 34.37% (11/32), respectively. In the chemotherapy group (n=28) partial remission was reported in 2 cases, stable disease in 15 cases, progressive disease in 11 cases. Median survival was 4.17 months, survival rates for 3, 6, and 12 months: 64.3% (18/28), 28.6% (8/28), and 10.7% (3/28), respectively.

Read more details in this PDF.

Case series

Most of the 20 case series suggest beneficial effects in terms of improving symptoms, relieving pain, or reducing the dosage of pain killers, and increasing survival time in patients with advanced and inoperable pancreatic cancer using herbal formulae or individualised formulations of herbs with or without chemotherapy12-31. However, these studies lack scientific robustness due to the absence of controls, and the claimed effects need to be tested in clinical trials. The findings from these studies can be considered as hypothesis generating for future studies.

Experimental studies

An in vitro study on two Chinese herbal formulations in pancreatic cancer cell lines showed a growth inhibition effect. The authors recommended further in vivo and clinical therapeutic studies32.

Biologic mechanism

As active ingredients from the herbal preparations are largely undefined, biologic mechanism of the potential effect has not been clearly elucidated.

Bias

According to an empirical study by Vickers et al33, almost all Chinese acupuncture trials published in Chinese report positive results, and publication bias might be the major explanation. Since the studies in this summary were conducted and published in Chinese literature, the positive findings need to be interpreted with caution.

The clinical studies reviewed above did not report adverse effects from herbal preparations in patients with pancreatic cancer. However, there are reports of liver toxicity and kidney damage associated with using Chinese herbal medicines 34 35. In recent years, Chinese herbal medicines have become the leading cause of hepatotoxicity from herbs. Possible interactions between herbs and drugs may also exist 36 37. Studies indicate that taking antioxidants such as flavonoids could decrease or increase the effectiveness of some anti-cancer chemotherapy if taken at the same time 36 38.

During the recent years, more and more manufacturers of herbal medicines in China meet Good Manufacturing Practices. For practitioner-prescribed herbal decoctions, it is more difficult to assure the quality of both herbs and herbal preparations. Therefore, long-term use of herbs should be under close monitoring of liver and kidney functions.