| Refractory acute leukemia (RAL) is the domestic and international medical research focus, at present there is no unified and efficient treatment programs. Multidrug resistance (MDR) in leukemia is one of the primary mechanisms in the results of refractory or relapsed leukemia, but it is lacking reversal agents in clinical with low toxicity and broader target role. MDR reversal agents plus chemotherapy treatment in recent years is a new attempt to RAL. Now compounds, biological agents and many Chinese drugs has been proven available to reverse MDR in tumor/leukemia cell, Most of the passengers in vitro study stage, and there are adverse reactions, such as clinical efficacy is not satisfied with shortcomings, clinical application is restricted.Since the 1990s, our department launched a a large number of studies with traditional Chinese and western medicine to anti RAL. Advance basic research has confirmed that the alkaloids extracted from thunberg fritillary bulb which is widely used in clinical medicine in vitro and in animal experiments have reversed MDR of leukemia. It will increase resistance of acute leukemia cells anticancer drug concentration and lower resistance the expression of Pgp. Pre-Clinical Experimental Research also shows that the conventional chemotherapy combined with the powder of thunberg fritillary bulb for the treatment of acute leukemia. Clinical complete response rate was higher, especially for patients with refractory or relapsed leukemia patients better clinical remission rate. In addition, Caladium particles Slices with chemotherapy in the treatment of RAL Clinical studies also show the Chinese refractory leukemia improve clinical efficacy safe and reliable. On the basis of the above results, we are now choose three kinds of Chinese medicine—fritillary,fourstamen stephania root,szechwan lovage rhizome which more recognized resistance has reversed the active ingredient, among single ingredient and the compound, to make particles—formulation of compound fritillary particles, as a therapeutic drug. The contrast drug is the placebo "malt particles." We develop a standardized diagnostic RAL standards, draw up the the clinical research programs and forms for case observations, and develop uniform standards to assess the efficacy. Patients in such studies as the research objects, the clinical efficacy and safety evaluation as the main indicator, we have the clinical research of compound fritillary granular formula with chemotherapy in the treatment of RAL randomized, double-blind, multi-center.The information of all the cases is from 12 three-level hospitals which observed RAL patients from January 2004 to December 2006. The numbers of the drugs and the patients'group are random. The rate of the two groups is roughly 1:1. Along with a standard chemotherapy regimen, before the start of chemotherapy in three days the treatment groups or the control group granules which are under the blindness are used, 1 bag (10g)each time and 3 times a day. In addition, any kind of reversal of leukemia parallel is not used. All patients were treated for 14 days, a standard chemotherapy regimen for a treatment cycle. If a treatment cycle is ineffective, the patients can continue taking subject granules with the next cycle of chemotherapy and continue to be observed a course of treatment and charged for the other passengers.After exposing the blindness, we found that the 12 research center has collected 137 cases of RAL. 128 cases are chosen for the statistics and 64 of them are in the treatment group and the rest are in the contrast group. The results show that the basic information of the gender, age, disease type, and the duration of the two groups of patients is comparable and balanced.②The curative effect shows that CR cases in treatment group are 25 (39.1%), and those in control group are 16(25.0%),PR cases are 21(32.8%) and 17(26.6%),NR cases are 18(28.1%),and 31(48.4%),in two groups respectively, showing significant statistical difference(P<0.05).The availability (CR+PR) of treatment group is better than that of control group (71.9%>51.6%), with significant statistical difference (P<0.05).③Relation between typing and curative effect analysis shows that analyzed byχ2 test, the availability of treatment group in AML patients is better than that of control group,with statistical difference (P<0.05).④Relation between gender and curative effect analysis shows that In male patients, analyzed by rank sum test, the curative effect of treatment group is better than that of control group, with statistical difference (P<0.05).⑤Relation between course of disease and curative effect analysis shows that In patients whose course of disease shorter than 6 months, analyzed by rank sum test, the curative effect of treatment group is better than that of control group, with statistical difference (P<0.05).⑥After treatment, marrow archaeocyte of treatment group are slightly lower than those of control group. Analyzed by t test, there is no statistical difference (P>0.05)。⑦There is statistical difference (P<0.05) when comparing the average Hgb of treatment group after 2 weeks treatment and before treatment. WBC lower significantly in both group .Comparing WBC after and before treatment in treatment group, there is significant difference (P<0.001). In control group there is statistical difference(P<0.05). There is statistical difference(P<0.05)when comparing PLT counts before and after treatment in treatment group.⑧Only a small part of the patients have MDR relative protein examination. Analyzed according to the variance tendency, the improvement of Pgp and MRP of treat group are better those of control group.⑨There in no significant abnormality in safety indexes like liver and kidney function, ECG, urinary and stool routine examination in both groups.Above results show that comparing with treatment only with chemotherapy, we may get better clinical effect when treat with chemotherapy as well as Compoud granula prescription of thunberg fritillary bulb. CR, PR and effective rate of treatment group are significantly higher than those of control group. Compoud granula prescription of thunberg fritillary bulb may be more effective for male, those with AML and whose course of disease are shorter than 6 months. There are no apparent liver and kidney function destroy and digestive tract side effect in treat group. It shows initially that the improvement of MDR relative protein as Pgp and MRP of treatment group are better than that of control group, which may be its main mechanism of reversing function. In conclusion, Compoud granula prescription of thunberg fritillary bulb is a safe and effective MDR reversing drug which deserves further research.
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