Liqun Jia
China – Japan Friendship Hospital, Beijing, China
There has been a consensus of a strategy of comprehensive treatment for lung cancer among most oncologists. As a part of comprehensive treatment, TCM has got some achievements in synergy with chemotherapy & radiotherapy, prolonging life span, reducing adverse effect, improving QOL, et al. As an emerging therapy, immunotherapy has many concept alike with TCM. It’s a new direction for TCM research to combine with immunotherapy.
In recent years, there have been more and more fundamental and clinical researches for TCM treatment in lung cancer. More and more oncologist have become interested in TCM, for its unique concepts and philosophies, such as holism, multi-target and multi-stage treatment.
Improve short-term effect
The mechanisms of TCM treatment for lung cancer involves increasing immune function, inhibiting proliferation, inducing apoptosis, intervention of signaling pathway, reversion of multidrug resistance, et al. The most researched medicines are as follows.
Kanglaite(KLT) Injection/Capsule
KLT is a Chinese Patent Medicine. In TCM theory, KLT has the function of Tonifying Qi and Yin, Removing Cumulation and Stasis. Its effective constituent is Semen coicis triglycerides, which is extract of Coix lacryma. KLT has effect of synergy with chemo- therapy & radiotherapy, anti-cachexia, and pain killing for some advanced patients.
A fundamental research from Johns Hopkins University suggested KLT could inhibit tumor cell proliferation by Inhibits NF-kB and Protein Kinase C Signaling [1].
Another research suggested KLT combined with chemotherapy drug could improve effect of tumor-inhibition.[2]
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A clinical research suggested KLT combined with PVM regimen could improve the effect for NSCL. Meanwhile, KLT could improve KPS and reduce hematotoxicity of chemotherapy drug [3]. Another research suggested KLT combined with chemotherapy could prolong MTTP & MST, and improve one year survival rate.
Shenyi Capsule
Shenyi Capsule is also a Chinese Patent Medicine. Its effective constituent is Ginsenoside-Rg3, which is extract of Panax ginseng. Shenyi Capsule could improve the symptoms of Qi deficiency, enhance body immune function, and synergize the effect of chemotherapy & radiotherapy. Research suggested Ginsenoside-Rg3 has functions of pro-apoptotic, proliferation & metastasis inhibition, anti-angiogenesis, et al.
Elemene Injection
Elemene Injection is another Chinese Patent Medicine. Its effective constituent is β-Elemene, which is extract of Curcuma zedoaria. Many researchers suggested Elemene Injection is effective for malignant pleural effusion & malignant and some solid tumor. The mechanism is related to pro-apoptotic, proliferation & metastasis inhibition, reversion of multidrug resistance, et al.
Reduce adverse Effect of Chemotherapy & Radiotherapy Chemotherapy-induced peripheral neuropathy (CIPN)
CIPN is a common dose-limiting side effect in peripheral nervous by chemotherapy, many chemotherapy drugs for lung cancer can induce CIPN, such as platinum, paclitaxel, vincristine.
A clinical research suggested Chinese medicine LC07 for external use could effectively reduce the pain of CIPN & systematic with good safety [4]. Other interrelated experiments found, external use of Chinese medicine LC07 could improve the changes in behavioristics under the temperature and mechanical stimulation, as well as accelerate the sensory nerve conduction velocity (SNCV) of coccygeal nerve & the contents of nerve growth factors (NGF) in plasma of rats with peripheral nerve toxicity induced by oxaliplatin. Moreover, LC07 could reduce the neuropathic pain, through inhibiting harmful signal transmission induced by activation of astrocyte in spinal dorsal horn.
Targeted therapy-induced skin injury
Targeted therapy of lung cancer is a treatment with development prospect.
However, its side effects are depressing. The most common one is skin injury (acne rash, skin dryness, etc.).
A clinical research suggested Chinese medicine ZY-06 for external use has significant curative effect on EGFRIs related acne rash, in alleviating acne rash and
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relieving pruritus, with little adverse reactions [5].Another research suggested TCM Moistening Cream had better efficacy than urea ointment in alleviating skin rhagadia, desquamation and pruritus. Moreover, TCM Moistening Cream took effect more quickly, healed and repaired skin in shorter time.
Radiation-induced pulmonary injury
Radiation-induced pulmonary injury is an inflammatory reaction of lung after Radiotherapy. A clinical suggested Pingfei oral liquid (PFOL) could reduce the incidence of Radiation pneumonia and pulmonary fibrosis[6]. Fundamental research showed that PFOL could inhibit proliferation and induce apoptosis of lung fibroblasts, regulate immune activity on Th1/Th2 type cytokines, and reduce the aggregation of mast cells, those may contribute to its protective effect on radiation—induced lung injury.
Joint treatment of TCM & immunotherapy Shenqi fuzheng Injection
Shenqi fuzheng Injection (SFI) is extracted from Codonopsis (or ginseng) and Radix Astragali. SFI could nourish Qi supplement Zheng. It is usually used in lung cancer patients, with TCM syndrome of physically and mentally fatigued, weak breath, disinclination to talk, spontaneous perspiration, dizziness. SFI could regulate immunity of NSCLC patients, increaCD3+, CD4+, CD41/CD8+, and improve curative effects of anti-cancer treatment.
Ginseng polysaccharides Injection
Randomly controlled trails reported effects of Ginseng polysaccharides Injection (GPS) plus dendritic cells (DC) in treating NSCLC patients. The results showed PFS (Progression-Free-Survival) in DCs+GPS group (16.39±2.60 months) was significantly longer than PFS in DCs control group (14.68±2.85 months).Th1 cytokines (INF-γ, IL-2) and the ratio of Th1/Th2 cytokines (INF-γ/IL-4, IL-2/IL-5) were significantly higher in the DCs+GPS group than in the DCs control group [7]. Conversely, FACT-L scores and Th2 cytokines (IL-4, IL-5) were significantly higher in the control group than in the DCs+GPS group. In vivo administration of ginseng berry extract (GB) promoted up-regulation of CD86, MHC class I and MHC class II and production of IL-6, IL-12 and TNF-α in mouse spleen DCs. GB also promoted the generation of Th1 and Tc1 cells. Ginseng polysaccharides (NGP) could stimulate the maturation of murine BMDCs, increase expression of MHC II, CD80, CD86, CD83, CD40 and secretion of higher level of IL-12 and low level of TNF-α.
Astragalus polysacharin
Astragalus polysacharin (APS) could accelerate the mature of human peripheral blood mononuclear cells (PBMCs) and increase expression of CDla, CD80 and
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CD86. APS induced mature DCs could stimulate the proliferation of allogeneic T lymphocytes and significantly increased the levels of IL-12 and IFN-γ in co-culture supernatant. Dendritic cell potently inhibit the tumor growth in vivo and improve the survivals of tumor bearing mice. The mechanism is possibly related to the generation of the antitumor cytokines IL-12 and TNF-α [8]. A Clinical study entitled on “optimization of TCM herbs based on constitution plus DC in treating NSCLC and CRPC” is ongoing in integrative oncology department, China-Japan friendship hospital. This study has included 20 NSCLC patients. Preliminary results show SFI plus DC treatment has excellent clinical effects and is safety in use.
References
1. Ju-hyung Woo. Coix Seed Extract, a Commonly Used Treatment for Cancer in China, Inhibits NF-kB and Protein Kinase C Signaling. Cancer Biology & Therapy. 2007;6:12,2005–2011.
2. Dapeng Li. Study of Kanglaite Injection Combined with Chemotherapeutic Drugs in Inhibiting the Growth of Transplanted Human Lung Cancer A549 in Nude Mice Traditional Chinese Drug Research &
Clinical Pharmacology. 2005,02:109–111+115.
3. Chengxu Cui, Junling Li, Xuezhi Hao, Datong Chu, Jinwan Wang. Observation of treatment of KLT Injection combined with PVM regimen in advanced NSLC [J]. Journal of QiLu Oncology, 1997, 04:72–73.
4. LOU Yan-ni, TIAN Ai-ping, ZHANG Xia, et al. Randomized, multi-center, double-blinded, controlled clinical trial of external treatment of TCM on peripheral neuropathy caused by chemotherapy[J]. China Journal of Traditional Chinese medicine and Pharmacy, 2014, 29(08):2682–2685.
5. WANG Hong-yan, ZOU Chao, CUI Hui-juan, et al. EGFRIs-related rash treated with external Chinese medicinal with actions of clearing heat and draining dampness in 120 cases[J]. Journal of Beijing University of Traditional Chinese Medicine, 2013, 20(04):14–17.
6. CHENG Zhi-qiang, ZHANG Jia, LIU Xuan, et al. Effects of Pingfei oral liquid in the radiotherapy of patients with non-small-cell lung carcinoma[J]. Journal of China-Japan Friendship Hospital, 2009, 23(06):334–336.
7. MA Jun-jie, XU Bin, LIU Hui-ping, ZHOU Chun-xiang. Clinical study on the intervention effect of Ginseng Polysaccharide Injection combined with DC on Th1/Th2 cells of NSCLC patients. CJTCMP.
2014, 29(8):2672–2675.
8. QIU Bo, ZING Xueš ping, WU fi-biao, CHEN Dan-dani, LIU Xiao-qing. Anti-tumour Effects of Dendritic Cell Vaccines Induced by Astralagus Polysaccharides on S180 Tumor-bearing Mice. Nan Jing Zhong Yi Yao Da Xue Xue Bao. 2015, 01:44–47.