|Year : 2014 | Volume
| Issue : 5 | Page : 75-78
Evaluation of sodium cantharidinate/vitamin B6 in the treatment of primary liver cancer
Hejun Shao, Guohu Hong, Xinhua Luo
Department of Infection Diseases, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China
|Date of Web Publication||30-Aug-2014|
Department of Infection Diseases, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550002
Source of Support: None, Conflict of Interest: None
Objective: The present study evaluated the treatment effectiveness of sodium cantharidinate/vitamin B6 in patient with middle/late stage primary liver cancer.
Materials and Methods: A 3-month follow-up study on 104 patients with primary liver cancer was carried out. Regular medication treatment was applied to 41 patients and sodium cantharidinate/vitamin B6 combined with the regular medication was applied to 63 patients. The treatment effectiveness and prognosis were evaluated using the statistical methods.
Results: At the end of the treatment, no significant difference was detected between the two groups; 1-month follow-up survey showed that in the treatment group, the death rate was lower, the treatment gain was maintained longer and the tumor morphology was maintained better, compared with the control group; 3-month follow-up study showed that there was not significance difference between the two groups.
Conclusion: Sodium cantharidinate/vitamin B6 might be used as auxiliary drug in patients with primary liver cancer and could improve the treatment outcomes for a short-term period.
Keywords: Primary liver cancer, sodium cantharidinate/vitamin B6, treatment effectiveness
|How to cite this article:|
Shao H, Hong G, Luo X. Evaluation of sodium cantharidinate/vitamin B6 in the treatment of primary liver cancer. J Can Res Ther 2014;10, Suppl S1:75-8
| > Introduction|| |
Sodium cantharidinate is an effective antitumor medicine that has been tested in clinical practice. It directly inhibits multiple malignant tumors, has low toxic/adverse effects, and therefore is a safe auxiliary antitumor medicine. , In recent years, researchers have confirmed through in vitro experiments that sodium cantharidinate and its derivatives directly kill the liver cancer cell lines, which provided the favorable theoretical basis for the application of sodium cantharidinate in treatment of primary liver cancer. 
Sodium cantharidinate/vitamin B6 is a combination of sodium cantharidinate and vitamin B6, and has the pharmacological characteristics of both sodium cantharidinate and vitamin B6. Most patients with primary liver cancer suffer from discomfort such as nausea and vomiting, which can be alleviated by vitamin B6. Therefore sodium cantharidinate/vitamin B6 has dual effects on both the causes and symptoms of primary liver cancer. Sodium cantharidinate/vitamin B6 is currently a major auxiliary drug in the treatment of primary liver cancer in clinic. It is widely investigated and used. However, the corresponding clinical research is rare, and the work that has been done mostly used the degree of the improvement in symptoms as the evaluation criteria for drug effectiveness. The present study applied the objective data as the evaluation criteria to study the treatment effectiveness of sodium cantharidinate/vitamin B6 in patients with middle-late stage liver cancer. It provided the evidence-based support for the application of sodium cantharidinate/vitamin B6 in the treatment of primary liver cancer and would further guide the development of relevant medication regiment.
| > Study design|| |
During the period from January 2011 through November 2012, 298 patients with the primary liver cancer were admitted into the Department of Infectious Diseases in Guizhou People's Hospital. Among them, 261 cases were diagnosed using imaging method, 37 cases were diagnosed using needle biopsy, and 70 cases refused further treatment and therefore were released from the hospital. One hundred and forty-two patients did not present surgery indications according to the consultation results from the Division of Hepatobiliary Surgery; 41 patients presented surgery indications, however, they and their families refused to receive the surgery treatment; the remaining 45 patients presented the surgery indications, agreed to accept the surgery treatment, and therefore were transferred to the Division of Hepatobiliary Surgery; 125 patients did not present the chemotherapy indications according to the consultation results from the Oncology Department; 32 patients presented chemotherapy indications, but they and their families refused to receive the chemotherapy; the remaining 26 patients were transferred to the Oncology Department; a total of 157 patients stayed to continue their treatment in the Department of Internal Medicine.
Diagnosis and Treatment Protocols
Twenty-three patients had severe kidney defects with Model for End-Stage Liver Disease (MELD) , score >40, KPS <30, and ZPS-WHO <4. They were in critical conditions and would not be included in the present study. Thirty patients were subject to transarterial chemotherapy and would not be included in the present study. The remaining 104 patients were only subject to the medication treatment in the Department of Internal Medicine. They were randomized into two groups, treatment (combined medication) group and control group, according to whether or not the sodium cantharidinate/vitamin B6 (50 ml, QD) would be applied. Standard treatment lasted for 2 weeks. If the treatment outcomes were not satisfactory, the patients would be subject to an extra week of medication. If the outcomes were still unsatisfactory, they would continue their inpatient treatment and be excluded from the study.
The follow-up time points were 1 and 3 months after the treatment. During the follow-up survey, the patients were called back and underwent the relevant physical examinations. Child-Turcotte-Pugh score and MELD score were calculated for each patient. The patients' liver conditions were also evaluated using enhance computed tomography (CT) imaging and RESIST standards. 
Counts data comparisons were performed using Chi-square (χ2 ) test and the quantitative data comparisons were performed using t-test. Life-Tables analysis was performed to generate the survival curve. Wilcoxon test was used to compare the survival curves.
| > Results|| |
One hundred and four patients were included in the study. Among them, 63 received the sodium cantharidinate/vitamin B6 treatment in addition to the regular medication treatment, and were considered to be the treatment group; whereas 41 patients received only regular medication treatment and were considered to be the control group. The baseline information between these two groups was not significantly different, as shown in [Table 1].
|Table 1: The baseline information about the patients who were included in the present study |
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Five patients died during the treatment, and 13 patients needed adjusted treatment protocol due to the disease progression or did not meet the standards to be released from the hospital after 3 weeks of treatment. These 18 patients did complete the study. Ten patients died within a month of treatment, 11 patients were retreated within a month, 3 patients were lost to follow-up or refused to be interviewed; 14 patients died during 1-3 months after the treatment, 16 patients were retreated during 1-3 months after the treatment, 11 patients were lost to follow-up or refused to be interviewed. The follow-up of the patients were shown in [Table 2].
No significant differences in the treatment outcomes were detected between the treatment group and the control group. Relatively satisfactory outcomes were obtained in most patients who underwent the combined medication or regular medication, and MELD scores were improved in both groups at the end of the treatment. One-month follow-up survey showed that 32% of the patients in the control group needed to be retreated due to the disease progression, whereas in the treatment group this percentage was only 6.25%, indicating the statistically difference (P = 0.01); imaging results showed that the tumor morphology in patients in the treatment group presented partial response (PR) (15.56%), although this morphology in most of the patients remained with no change (NC) (64.44%); in the control group, none of the patients presented PR, and about 50% of the patients presented progressive disease (PD) (47.06%), suggesting the statistical difference between the two groups (P = 0.04). Three-month survey showed that most of the patients in both groups could not remain NC, with death percentage reaching 29.73% and 21.43%, respectively; most of the patients in both groups needed to be re-treated due to the disease progression and imaging results showed that most of the patients (70.59% vs. 75.00%) presented disease progression.
Three-month survival rate analysis showed that no significant differences were detected between the two groups (P = 0.984), however, 60-day survival rate in the treatment group was higher than that in the control group [Figure 1]; the percentage of the patients who needed to be retreated within 3 months did not show significant differences (P < 0.01). The effective stable time period was longer in the treatment group; whereas in the control group, most patients needed to be retreated within a shorter period of time due to the disease progression. Particularly, within 20 days, about 30% of the patients in the control group needed to be retreated [Figure 2].
|Figure 1: Survival rates analysis during the 3-month follow up in the two groups|
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|Figure 2: Analysis of the patients' stable time period after 3 months of treatment in the two groups|
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| > Discussion|| |
The present study selected the objective criteria to evaluate the treatment outcomes of the sodium cantharidinate/vitamin B6 in patients with primary liver cancer and the criteria  included the following three aspects: Improvement in liver function, changes in tumor morphology and ending conditions of the patients. Compared with the previous studies, the criteria system in the present study was more objective. ,,,,
In our study, we have found that sodium cantharidinate/vitamin B6 did not affect the protection of the liver function by the regular treatment protocol; however, within 1 month after the treatment, most patients with primary liver cancer who received the treatment of cantharidinate/vitamin B6 lived longer than those who received regular treatment, their treatment gains were maintained longer in the former group, and the progression of the tumor morphology were delayed for a short-term period of time. These results provided strong clinical evidence for the application of cantharidinate/vitamin B6 in the treatment of primary liver cancer.
In contrast to many previous studies, ,, the present study selected sodium cantharidinate/vitamin B6 alone as antitumor drug in patients who did not present chemotherapy indication or refuse chemotherapy, and confirmed that sodium cantharidinate/vitamin B6 alone could improve the patients' life conditions and delay the progression of the solid tumor morphology in liver, providing more insights into the treatment of patients who had the middle/late stage primary liver cancer and did not have the surgery/chemotherapy indications.
In clinical practice, many researchers used hepatic arterial chemoembolization (HACE) to apply the sodium cantharidinate or other compound medicine to treat the patients with middle/late stage liver cancer, and gained satisfactory results. ,,, However, HACE has some limitations. First of all, chemoembolization is not applicable to the patients who have late stage/metastatic cancer. Secondly, administration of single dose of medication cannot maintain its blood concentration for long period of time. Thirdly, it is invasive with poor patient compliance. The present study applied sodium cantharidinate/vitamin B6 solely via i.v. and similarly confirmed their effectiveness. Most patients maintained their treatment gain for about one month. The data provided evidence-based support for the application of sodium cantharidinate/vitamin B6 in the clinical practice.
| > References|| |
|1.||Tsauer W, Lin JG, Lin PY, Hsu FL, Chiang HC. The effects of cantharidin analogues on xanthine oxides. Anticancer Res 1997;17:2095-8. |
|2.||Lin LH, Huang HS, Lin CC, Lee LW, Lin PY. Effects of cantharidinimides on human carcinoma cells. Chem Pharm Bull (Tokyo) 2004;52:855-7. |
|3.||Yeh CB, Su CJ, Hwang JM, Chou MC. Therapeutic effects of cantharidin analogues without bridging ether oxygen on human hepatocellular carcinoma cells. Eur J Med Chem 2010;45:3981-5. |
|4.||Onaca NN, Levy MF, Sanchez EQ, Chinnakotla S, Fasola CG, Thomas MJ, et al. A correlation between the pretransplantation MELD score and mortality in the first two years after liver transplantation. Liver Transpl 2003;9:117-23. |
|5.||Pagliaro L. MELD: The end of Child-Pugh classification?. J Hepatol 2002;36:141-2. |
|6.||Sohaib SA, Turner B, Hanson JA, Farquharson M, Oliver RT, Reznek RH. CT assessment of tumour response to treatment: Comparison of linear, cross-sectional and volumetric measures of tumour size. Br J Radiol 2000;73:1178-84. |
|7.||Montano-Loza AJ. New concepts in liver cirrhosis: Clinical significance of sarcopenia in cirrhotic patients. Minerva Gastroenterol Dietol 2013; 59:173-86. |
|8.||Zhang A. Effects of sodium cantharidate on quality of life in advanced liver cancer patients. Chin J Rehabil Theory Pract 2011;17:679-81. |
|9.||Zhang MJ, Zuo CF. Clinical efficacy of sodium cantharidate vitamin B6 injection combined with chemotherapy in treatment of liver cancer. J Pract Oncol 2011;26:50-2. |
|10.||Fan CX. The observation of the effects of disodium norcantharidate in the treatment of advanced primary liver cancer. J Basic Clin Oncol 2010;23:50-51. |
|11.||Yin F, Yao SK, Cai HY. The efficacy of sodium cantharidate vitamin B6 in treatment of liver fibrosis in the patients of liver cancer. J Hepatopancreat Surg 2009;21:296-7. |
|12.||Zeng L, Liu YL, Lui XT. The efficacy of sodium cantharidate vitamin B6 in treatment of liver cancer. J Hebei Med Univ 2009;30:596-7. |
|13.||Wang XF, Luo XH. Adjuvant treatment with disodium cantharidinate and vitamin B6 injection for patients with hepatocellular carcinoma: A Meta analysis based on randomized controlled trials. J Inter Oncol 2014;41: 69-73. |
|14.||Tian XL, Yang P. Clinical efficacy of treatment of liver cancer with combined sodium cantharidate vitamin B6 injection and TACE therapy. Chin J Clin Oncol Rehabil 2006;13:351-3. |
|15.||Wang ZG, Tao H, Zhang LY, Liu DC, Xiao HL, Du WH. Effect of intra-abdominal volume increment on kidneys in minipigs with intra-abdominal hypertension after hemorrhagic shock and resuscitation. Mil Med Res 2014;1:4. |
|16.||Liang BL, Nan YM, Liu SM. The efficacy of sodium cantharidate vitamin B6 in liver function and blood cell count after TACE therapy. China Med 2010;5:701-2 |
[Figure 1], [Figure 2]
[Table 1], [Table 2]