Category Archives: Chapter 8 Injectables and Cancer Research

De Li Sheng Injection

Cancer: Lung

Action: Chemo-protective, chemo-enhancing

Ingredients: hong shen (processed/red Panax ginseng), huang qi (Astragalus membranaceus), sheng chan su (Bufo bufo gargarizans Cantor), sheng ban mao (crude Mylabris phalerata)

TCM functions: Invigorating qi, supporting Vital-qi, dissolving tumors and dispersing lumps.

Indications: qi deficiency and Blood stagnation type of primary liver cancer of middle and late stage.

Dosage and usage:

40-60 ml mixed with 500 ml of 5% glucose injection or normal saline for intravenous drip, once daily. In each course of treatment, the dosage of first treatment should be reduced to half and medicinal liquid should be diluted to no lower than 1:20, the speed should be no more than 15 drips every minute. 45 days as a course of treatment. A new course should begin after 1 one week”s interval.

Chemotherapy

A meta-analysis of 10 studies showed that, when Delisheng Injection combined with chemotherapy group was compared with chemotherapy group, the relative risk (RR) to the effective rate (CRPR) was 1.29 and 95% confidence interval (CI) was [1.11, 1.50]; RR to KPS scale improved rate was 1.81 and 95%CI was [1.53, 2.15]. The incidence of adverse reactions was lower in patients treated with Delisheng Injection combined with chemotherapy than in those treated with chemotherapy alone. Significant difference was noted in the incidence of alopecia, liver damage phlebitis, between the two groups of patients (Huang, Lai, & Ye, 2013).

Lung Cancer

Delisheng Injection (DLS) single-agent has a satisfying inhibition effect in PGCL3 cell line and DLS might enhance the inhibition effect of DDP on cancer metastasis. Research by Dong, et al., (2013) provided an experimental basis about the treatment on highly metastatic lung cancer.

NSCLC; Chemotherapy

There were significant differences observed in hematological toxicity and gastrointestinal toxicity and clinical symptoms (P < 0.05) between the control group, treated with only Gemcitabine and Platinum (GP), and the treatment group of combined Delisheng and GP. The change of the scores of the Karnofsky Performance Status scale (KPS) and body weight was significant in the treatment group compared with the control group (P < 0.05). The combination of Delisheng injection and (Gemcitabine and Platinum) GP can be used to treat non-small-cell lung cancer postoperatively, which can improve the clinical symptoms and reduce the toxicity during chemotherapy and enhance the patient”s tolerance to chemotherapy (Wu, Ye, & Xie, 2010).

The therapeutic effect of Delisheng (DLS) combined with chemotherapy is better than that of chemotherapy alone, in the treatment of patients with stage III-IV non-small-cell lung cancer. It can improve efficacy, quality of life, and reduce the side-effects of chemotherapy, while promoting hematopoiesis (Zhou & Ni, 2009).

767 participants (patients) in 10 homogeneous studies were included in randomly controlled trials that met the enrolling criteria. The meta-analysis of the 10 studies showed that, when Delisheng Injection combined with chemotherapy group was compared with chemotherapy group, the relative risk (RR) to the effective rate (CRPR) was 1.29 and 95% confidence interval (CI) was [1.11, 1.50]; RR to KPS scale improved rate was 1.81 and 95%CI was [1.53, 2.15].

The incidence of adverse reactions was lower in patients treated with Delisheng Injection combined with chemotherapy than in those treated with chemotherapy alone. Significant difference was noted in the incidence of alopecia, liver damage phlebitis, between the two groups of patients. Conclusion: Delisheng Injection combined with chemotherapy has beneficial effects in the treatment of NSCLC (Huang et al., 2013).

References

Dong, X-l., Gong, Y., Chen, Z-z. (2013). Delisheng injection  a Chinese medicinal compound, enhanced the effect of cis-platinum on lung carcinoma cell line PGCL3. Chinese Journal of Integrative Medicine.


Huang, Y.l., Lai, D., Ye, Y.(2013) A meta-analysis of Delisheng Injection combined with chemotherapy in the treatment of non-small-cell lung cancer. Lu Shou Yi Xue Yuan Xue Bao. 2013, 36(2): 139-144


Wu, X., Ye, Sy., Xie, Bl. (2010). Effect of Delisheng Injection with Chemotherapy on Reducing Toxicities in Postoperative Treatment for Non-Small-Cell Lung Cancer. Zhong Guo Zhong Xi Yi Jie He Wai Ke Za Zhi, 16(4): 412-414.


Zhou, J., Ni, S. (2009). The Therapy of DLS combined with chemotherapy in stage Ⅲ-Ⅳ non-small-cell lung cancer. Lin Chuang Fei Ke Za Zhi, 14(5): 642-644.

Ai Di Injection (ADI)

Cancers: Breast, colorectal., glioma, lung

Action: Chemo-sensitizer, cytostatic, radio-sensitizer

 

Ingredients: Mylabris phalerata (ban mao), Panax ginseng (ren shen), Astragalus membranaceus (huang qi).

TCM functions: Clearing Heat, removing Toxin, resolving stagnant Blood, dissolving lumps.

Indications: Primary liver cancer, lung cancer, colorectal cancer, malignant lymphoma, and gynecological malignancies.

Dosage and usage:

For adults: 50-100ml, mixed with 400-500ml of 0.9% NaCl injection or 5-10% glucose injection for intravenous drip, once daily.

When combined with radiotherapy or chemotherapy, the course of treatment is synchronized to radiotherapy or chemotherapy.

Application before or after the surgery: 10 days as a course of treatment.

Intervention treatment: 10 days as a course of treatment.

Single application: 15 days as a cycle, with 3 days interval., 2 cycles as a course of treatment.

 

Cachexia patients in advanced stage: 30 consecutive days as a course of treatment (Drug Information Reference in Chinese: See end).

 

Glioma; Radio-sensitization

The inhibition ratio was determined by MTT assay, the change in the cell-cycle was analyzed by flow cytometry and the expression of cyclin B1 and Wee1 was detected by Western blot analysis. The reproductive activity of the group treated with irradiation (IR) and Aidi injection was suppressed significantly, and the cloning efficiency and divisional index also declined. Aidi injection (15 µg/ml) induced G2/M phase arrest in the cell line after 48 h.

 

Aidi injection (ADI) is effective in radio-sensitization. The possible mechanisms involved may be associated with G2/M phase cell arrest, the down-regulation of cyclin B1 and up-regulation of Wee1 expression, which influences cell size by inhibiting the entry into mitosis, through inhibiting Cyclin-dependent kinase 1 (Xu, Song, Qin, Wang, & Zhou, 2012).

 

Breast Cancer

ADI significantly inhibited the proliferation of MCF-7 cells in a dose-dependent manner. The IC50 of ADI was 55.71 mg/mL after treatment for 48 h. The 60 mg/mL ADI was used as the therapeutic drug concentration. Microarray analysis identified 45 miRNAs that were up-regulated and 55 miRNAs that were down-regulated in response to ADI treatment. Many ADI-induced miRNAs were related to breast cancers. The 12 potential target genes of mir-126 were predicted by both TargetScan and PicTar software.

 

The miRNA may serve as therapeutic targets for ADI, and its modulation of expression is an important mechanism of ADI inhibition of breast cancer cell growth (Zhang, Zhou, Lu, Du, & Su, 2011).

 

Colorectal Cancer; FOLFOX4

A consecutive cohort of 100 patients was divided into two groups. The experimental group was treated with a combination of Aidi injection and FOLFOX4, while the control group was only administered FOLFOX4. After a minimum of two courses of treatment, efficacy, quality of life, and side-effects were evaluated.

 

The response rate of the experimental group was not significantly different compared to the control group (P > 0.05). However, there were significant differences in clinical benefit response and KPS score. In addition, adverse gastrointestinal reactions and the incidence of leukopenia were lower than that of the control group (P < 0.05).

Aidi injection, combined with FOLFOX4, is associated with reduced toxicity of chemotherapy, enhanced clinical benefit response, and improved quality of life in patients with advanced colorectal cancer (Xu, Huang, Li, Li, & Tang, 2011).

 

NSCLC

Ninety-eight cases of advanced NSCLC were randomly divided into two groups: a trial group and control group. In the trial group Navelbine/Cisplatin (NP) plus Ai Di Injection (ADI) (60-80 ml) was administered intravenously, via dissolution in 400 ml of normal saline, per day for 8-10 days. In the control group, only NP chemotherapy was administered at the dosages of: Navelbine (25 mg/m², d1, 8) and Cisplastin (40 mg/m², d1-3). Each patient received at least two cycles of treatment.

 

The effective rate in the trial group and the control group was 53.1% and 44.9% respectively, without significant difference between the two groups (P > 0.05). However, the rate of progression, adverse reactions in the bone marrow, digestive tract, and immune function in the trial group were all lower than those in the control group (P < 0.05). In addition, improvement in Karnofsky score in the trial group was higher than that in the control group (P < 0.05).

 

A chemotherapy regiment of NP, combined with ADI, shows benefit in the treatment of advanced NSCLC. AI could minimize the adverse reactions of chemotherapy, and improve the quality of life in patients with NSCLC (Wang et al., 2004).

 

NSCLC; Meta-analysis

PubMed (1980-2008), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2008), EMBASE (1984-2008), CancerLit (1996-2003), CBMdisc (1980-2008), CNKI database (1980-2008), Wanfang database (1980-2008), and Chongqing VIP database (1980-2008) were searched. Relevant Chinese periodicals were manually searched as well. All randomized controlled trials comparing Aidi Injection with other treatment methods of NSCLC were included. Two reviewers selected studies, assessed the quality of studies, and extracted the data independently.

 

Fourteen randomized controlled trials were included in the meta-analysis, but unfortunately, the quality of reports of the 14 included studies were poor. Aidi Injection combined with cobalt-60, or navelbine and platinol (NP), showed statistically significant differences in improving the response rate, compared to the use of cobalt-60 alone (P = 0.0002) or NP alone (P = 0.04). However, Aidi Injection combined with etoposide and platinol (EP), taxinol and platinol (TP) or gamma knife showed no significant differences when compared with single use of EP (P=0.60), TP (P=0.16) or gamma knife (P=0.34), respectively. The RR and 95% CI of EP, TP, and gamma knife were 1.17 [0.65, 2.09], 1.27 [0.91, 1.78] and 1.08 [0.92, 1.26] respectively.

 

Six studies indicated that Aidi Injection, combined with NP or gamma knife, could improve quality of life. Six studies showed that Aidi Injection, combined with NP or TP, could improve the bone marrow’s hematopoietic function. The results of the meta-analysis indicate that Aidi Injection may have adjuvant therapeutic effects in the treatment of NSCLC patients. However, sample sizes are small, study quality is poor, and the existence of publication bias had been found. The effects of Aidi Injection need to be confirmed by large multicenter randomized controlled trials (Ma, Duan, Feng, She, Chen & Zhang, 2009).

 

NSCLC; Neo-adjuvant Chemotherapy

Sixty patients, with stage IIIA non-small-cell lung cancer (NSCLC), underwent two courses of bronchial arterial infusion (BAI) chemotherapy, before tumor incision. They were assigned to either the treatment or control group, using a random number table. Thirty patients were allocated to each. An ADI of 100 mL, added into 500 mL of 5% glucose, was given to the patients in the treatment group via intravenous drip. Treatment was once a day, beginning 3 days prior and throughout each of two 14-day courses of chemotherapy.

 

Levels of T-lymphocyte subsets, natural killer cell activity, and interleukin-2 in peripheral blood were measured before and after the treatment. The effective rate in the treatment group was higher than that in the control group (70.0% vs. 56.7%, P < 0.05).

 

Moreover, bone marrow suppression and liver function damage (P < 0.05) was less in the treatment group relative to the control. Cellular immune function was suppressed in NSCLC patients, but was ameliorated after treatment, showing a significant difference when compared to the control group (P < 0.05).

 

ADI could potentially act as an ideal auxiliary drug for patients with stage IIIA NSCLC, receiving BAI neo-adjuvant chemotherapy, before surgical operation. It could enhance the effectiveness of chemotherapy, ameliorate adverse reactions, and elevate patient’s cellular immune function (Sun, Pei, Yin, Wu & Yang, 2010).

 

References

Ma, W.H., Duan, K.N., Feng, M., She, B., Chen, Y., & Zhang, R.M. (2009). Aidi Injection as an adjunct therapy for non-small-cell lung cancer: a systematic review. Journal of Chinese Integrative Medicine, 7(4), 315-324.

Sun, X.F., Pei, Y.T., Yin, Q.W., Wu, M.S., & Yang, G.T. (2010). Application of Aidi injection in the bronchial artery infused neo-adjuvant chemotherapy for stage III A non-small-cell lung cancer before surgical operation. Chinese Journal of Integrative Medicine, 16(6), 537-541.

Wang, D., Chen, Y., Ren, J., Cai, Y., M. Liu, M., & Zhan, Q. (2004). A randomized clinical study on efficacy of Aidi injection combined with chemotherapy in the treatment of advanced non-small-cell lung cancer. Journal of Chinese Integrative Medicine, 7(3), 247-249.

Xu, H.X., Huang, X.E., Li, Y., Li, C.G., & Tang, J.H. (2011). A clinical study on safety and efficacy of Aidi injection combined with chemotherapy. Asian Pacific Journal of Cancer Prevention, 12(9), 2233-2236.

Xu, X.T., Song, Y., Qin, S., Wang, L.L., & Zhou, J.Y. (2012). Radio-sensitization of SHG44 glioma cells by Aidi injection in vitro. Molecular Medicine Reports, 5(6), 1415-1418.

Zhang, H., Zhou, Q.M., Lu, L.L., Du, J., & Su, S.B. (2011). Aidi injection alters the expression profiles of microRNAs in human breast cancer cells. Journal of Traditional Chinese Medicine, 31(1), 10-16.

Acteoside

Cancer: Melanoma; metastasis

Ohno et al. (2009) suggests that acteoside injection, isolated from Plantago lanceolata showed suppressive effect on lung metastasis of B16 melanoma cells. Male C57BL/6 mice were injected intravenously with 2 x 10(5) of B16 melanoma cells, while acetoside at a dose of 50 mg/kg was administered intraperitoneally every other day from 13 d before B16 melanoma cell injection until all mice had succumbed to the metastatic tumor burden in the lung.

Administration of acteoside prolonged survival time significantly and the average survival time was 63.3 +/- 3.4d compared with 52.1 +/- 2.5d in control mice.

Reference

Ohno, T., Inoue, M., Ogihara, Y., Saracoglu, I. (2012) Anti-metastatic activity of acteoside, a phenylethanoid glycoside. Biological & Pharmaceutical Bulletin, 25(5):666-8. doi: 10.1248/bpb.25.666

Yun Zhi (Polystictinum)

• Ampoule (containing 40 mg of its polysaccharide): 1 ampoule IM bid, 4 weeks as one course, another course may be continued after an interval of 2 weeks; or 3-4 ampoules added in 10% glucose solution 300 ml IV for drips daily for 10 days, and then continue for 10 days after an interval of 1-2 weeks.

• Indications: none noted in source text.

San Jiang Shan

(Ramulus et Folium Cephalotaxi Fortunei)

• Harringtonine injection: 1-6 mg added in 5-10% glucose 500 ml IV for drips daily, 5-7 days as one course, 1-3 courses may be applied at an 1-2 week intervals; homo-harringtonine, same dosage as harringtonine.

• Indications: this herb is mainly used as an anti-carcinogenic for acute non-lymphocytic leukemia such as acute myelocytic leukemia, acute monocytic leukemia, malignant lymphoma.

• Pharmacological action: 1) Harringtonine, homo-harringtonine, iso-harringtonine and deoxy-harringtonine are the anti-carcinogenic components, which interfere with the cell growth and mitotic activity, damage and inhibit the growth of S-stage cells and inhibit the synthesis of DNA. Harringtonine and homo-harringtonine are more effective for the interference of mitotic activity. 2) Inhibiting the hematopoeitic cells in bone marrow. 3) Causing irritant effect on digestive tract.

E Zhu (Rz. Zedoariae)

• 5% Oleum Zedoariae Ampoule: 5-10 ml topical injection qd for carcinoma of the cervix. 1% Curcumenol Ampoule: 2-4 ml topical injection qd for carcinoma of cervix. 30% Zedoariae Ampoule: 100-300 ml IV for drips qd for various kinds of tumors.

• Indications: carcinoma of cervix and various kinds of tumors as described above.

Shan Ci Gu (Bulbus Iphigeniae)

• Clochincine amide 10 mg: 10 mg IV for drips daily, total dosage 0.2-0.3g. This herb may cause nausea, vomiting, general pain, palpitation, alopecia, etc. or even leukocytopenia, so the dosage should be limited.

• Pharmacological action: Clochincine, one of its active components, and tis derivatives exerts an inhibiting effect on various kinds of sarcoma and parenchymatous liver cancer in experimental animals. It serves as inhibitor in the intermediate stage of cellular mitosis.

Zhu Ling (Polyporus Umbellatus)

• Ampoule (containing its polysaccharide): 40 mg IM once or twice daily.

• Indications: may be used together with chemotherapy and radiotherapy for cancers of the lung and liver and acute leukemia. [1]

Sources for point injection:

1. Therapeutics of Acupuncture and Moxibustion. Shi Min (Ed.) Medicine & Health Publishing Co. Hong Kong, 1996. ISBN: 962-300-079-0

All others: Chinese-English Manual of Common(ly)-Used (Herbs) in Traditional Chinese Medicine. 1993 Heilongjiang Education Press, Harbin. ISBN: 7-5359-0871-3

References:

Chu, JHK. (2010) http://alternativehealing.org/injection_solution_of_herbs.htm. Retrieved November 12 2013

Manitoba Health. (2003) APPENDIX – Routes of Drug Administration. Aug 2003 P.A2-1. http://www.ismp.org/Tools/errorproneabbreviations.pdf

Nursing Times. (2007) http://www.nursingtimes.net/nursing-practice/clinical-zones/prescribing/the-administration-of-medicines/288560.article

Drug Information Websites (China)

Drug Information [Chinese Language] (2000-12) http://ypk.39.net/manual/811434/0/ (Compound Ku Shen Injection)

 Drug information. [Chinese Language] (2000-12) http://ypk.39.net/manual/587514/0/ (Ai Di Injection)

Drug information. [Chinese Language] (2000-12) http://ypk.39.net/manual/589223/0/ (Cinobufotalin Injection)

Drug information. [Chinese Language] (2006-08)http://weichang.gzbaozhilin.com/Catalog/%E5%85%B6%E4%BB%96%E8%83%83%E8%82%A0%E8%8D%AF/xiaoaipingzhusheye-198.html (Xiao Ai Ping Injection)

Drug information. [Chinese Language] (2000-12) http://ypk.39.net/manual/502749/0/ (Kang Lai Te Injection)

Drug information [Chinese Language] (2000-12) http://ypk.39.net/manual/589149/0/ (Shen Qi Vital-qi Supporting Injection)

I.V. and I.M Injections