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Clinical Research on Using Elemene to Treat Glioma |
Abstract
Purpose: to
explore the clinical effect of using elemene to treat gliomas. Methods: 49
patients with glioma were chosen, 16 treated with elemene only, 33 treated with
elemene and chemotherapy drugs. Injection dose of elemene: for adults, 1000 mg/d,
alternating injection in the carotid artery and peripheral veins, with 20 days as
a course of treatment. Tumor size, clinical performance, survival time and side
effects were evaluated and compared before and after the treatment. Results: after
carotid artery and peripheral injection of elemene, the total efficiency was 46.94%
(CR14.29%, PR 32.65%); tumor sizes decreased by 30.89% ± 55.97% on average;
clinical symptoms showed different levels of improvement; the survival time of 32
patients were: <1y, 7 patients, > 1y , 14 patients, > 2y, 6 patients, >
3y, 5 patients. The efficiency rate of using elemene alone was 37.5%, that
using elemene and chemotherapy was 51.51%. Elemene did not cause bone marrow
suppression, gastrointestinal reactions, and other side effects. Conclusion: Elemene
did have anti-glioma function. In clinical application, the drug should be used
with adequate dosage for long enough, and recommended to be given via the
artery. Elemene can be used regularly in glioma patients, and recommended early
use. If other drugs do not work, patients can try elemene.
Key words:
brain tumor, drug therapy, glioma, elemene
Glioma is
the most common malignant tumors of the central nervous system, but
unfortunately, no breakthrough has been made in treating it. Over the past 20
years, the median survival time of glioma patients did not show any significant
growth, and all kinds of therapy fail to radically cure the disease, which has
become a most challenging and urgent issue for neurosurgeons. Elemene is a
non-cytotoxic anti-tumor drug developed by Chinese people. It had exact effect,
caused no bone marrow suppression, no resistance, and could improve the
immunity. And as a small molecule, the drug compound can pass the blood-brain
barrier, which is suitable for treating brain tumors. The effect in treating
glimoas with elemene is obvious, which may benefit more patients.
1 Material
and Methods
1.1 study object:
Candidate criteria (all the four requirements must be met): (1) patients that
had surgeries and that were pathologically confirmed, and patients that were
not operated on and diagnosed with clinical examinations and CT or MRI (2) patients
not suitable for having surgery/ another surgery or with residual and recurrent
symptoms after operation, (3) patients with blood, liver and kidney function
and generally normal ECG (4) patients that had completed the treatment with elemene
for at least one cause of treatment.
All the 84 glioma
patients treated with elemene during the recent 10 years in the affiliated
hospitals of
1.2
experimental grouping
grouping of glioma patients: (1) 16 patients were treated only with elemene, (2)
33 patients were treated with elemene in combination with the chemotherapy drugs.
1.3 method of treatment
Elemene watery agent 1%
1.4 Clinical
Evaluation
(1) CT and MRI inspection was done before and after the treatment, the tumor
size was compared; after statistical analysis, brain glimoa efficacy criteria 3
was used to assess the recent effects and calculate the efficiency.
(2) The clinical performance of patients was recorded as an index of judging
the clinical efficacy. (3) Analysis of survival time
1.5 toxicity evaluation
Systematic (such as bone marrow suppression, gastrointestinal symptoms, etc.)
and local symptoms were recorded after the treatment.
2 results
2.1 efficacy evaluation
The average tumor size decreased by 30.89 ± 1 55.97% after the treatment. The
efficacy in treating 49 patients: CR 7 (14.29%), PR 16 (32.65%), MR 8 (16.33%),
NC 8 (16.33%), PD 10 cases (20.41 %), with the total efficiency up to 46.94%
(23/49). The results were shown in table l
Table 1.
Comparison of the results of the two groups
|
|
Group
treated with elemene |
Group
treated with elemene and chemotherapy drugs |
|
Cases |
16 |
33 |
|
CR |
2
(12.50%) |
5
(15.15%) |
|
PR |
4
(25.00%) |
12(36.36%) |
|
MR |
3
(18.75%) |
5
(15.15%) |
|
NC |
4(25.00%) |
4
(12.12%) |
|
Efficiency
rate |
37 .50% |
51 .51% |
2.2 clinical performance
Before the treatment, 41 patients had headache, 17 had nausea and vomiting, 6
had epilepsy, 22 had hemiplegia, 1 had ataxia, 2 had olfactory hallucination, 6
had vision problems, 7 had aphasia. After the treatment, 13 patients had
headache, 5 had nausea and vomiting, 4 had epilepsy, 8 had hemiplegia, 1 had
ataxia, 1 had olfactory hallucination, 4 had visual impairment and 3 had
aphasia.
2.3
survival time
17 patients were missed in the follow- up, the survival time of 32 patients was
counted. Of the 32 patients, 13 died, of whom 8 died from astrocytomas, 4 died
from glimoas, the death of 1 patient was not analyzed pathologically. Their
survival time ranged from 4 months to 66 months. To the date of the statistics,
19 patients were alive. The survival time ranged from 9 months to 9 years (one
case of glioblastoma patients). The survival time of 32 patients with gliomas
was as follows: <1y, 7 patients; > 1y, 14 patients, > 2y, 6 patients,
>3y, 5 patients.
2.4 toxicity and side effects
The group treated only with elemene did not show bone marrow suppression and CT
/ MRI confirmed no occurrence of blood clots in the brain. A small number of
patients with carotid artery injection of elemene showed wetness and redness on
the same side of the neck and face, eye pain and tears, pharynx itch, which
soon resumed to normal after drug injection. When the speed of drug injection
was lowered and 2.5 mg dexamethasone was added with the drug, symptoms relieved
or disappeared. After many times of puncture, the wall of the blood vessel may
harden, but the drug could still be applied after a short rest or local
physical treatment. Liquid leakage to the surrounding tissue may cause
localized swelling and pain, which may be adsorbed one to two days later.
3
discussion
3.1 the anti-glioma effect of elemene: Glioma is the most stubborn malignant
tumor, which is mainly treated with a combination of surgery and radiotherapy
and chemotherapy at home and abroad. But the result is not optimistic, which is
determined by the anatomical and pathological features of glioma. Under the
existing conditions, it is impossible to completely remove glioma cells. Due to
the limitation of blood-brain barrier (BBB), chemotherapy drugs are mainly
Teniposide. In recent years, new methods were proposed, for instance, using
podophyllotoxin derivatives etoposide and radiotherapy together. The Phase II
clinical efficiency was 34.6 percent.
(CR 15.4%, PR19.270) [4]. In treating patients with reoccurred glimoas using Temozolomide, the Phase
II efficiency rate for 111 patients was 35% (CR8%, PR27%) [5]. 51 patients with
reoccurred gliomas after surgery and chemotherapy were treated with Procarbazine and
high-dose of tamoxifen. The effective rate was 29.5% (CR 4%, PR25.5%), etc. [6]
Elemene is a new
second category non-toxic anti-tumor drug. Elemene is separated from Ezhu
volatile oil. Ezhu is a curcuma plant that grows in
We found in the clinical that elemene had remarkably good anti-glioma
effect. In the group given carotid artery injection and peripheral intravenous
infusion of elemene, the total efficiency was 46.94 percent, on average tumor size
decreased by 30.89±55.97%. In the group that used elemene in combination with
other drugs, the efficiency was as high as 51.51 percent, of which some cases were
even clinically cured.
These results suggest that elemene could effectively treat glioma, its total
efficiency rate and patient survival period were significantly higher than the
report in literature at home and abroad. This is undoubtedly a new channel for
the treatment of glioma.
Only 1
patient showed serious complications. One side effect of carotid artery injection
of elemene was facial and eye wetness and redness. The reason may be some drug
went to the face via the external carotid artery, and fast injection can cause
facial wetness and redness. In addition, some high-concentration drugs may flow
along the ophthalmic artery and cause eye irritation. Slower injection and use
of 2.5 mg dexamethasone can reduce local symptoms and do not affect the
treatment.
3.2 evaluation In the clinical application of elemene, the following issues are
important:
We believe that as elemene
has the advantages of fewer side effects, immunity enhancement and causes no
drug-resistance, it is recommended to use the drug in high dose and for longer
period. The specific administration method is as follows: (1) for adults, 1000
mg/d, twice a day. Slow injection in the carotid artery of the affected side, and
in peripheral veins. 20 days as a course of treatment. If the tumor is in the
middle lane or bilateral lesions, the drug is given in bilateral carotid
arteries alternately. The brain stem and cerebellum tumors were mainly treated
with intravenous administration, for 1 to 2 times per week.
(2) It is recommended
to use elemene in combination with VM-26 and BCNU.
(3) It is recommended to use for 3 to 5 course of treatment, and even for 1
year if the effect is obvious.
Elemene had obvious effect on nearly 1/3 of glioma patients, most of whom were
reported smaller tumor size and relieved clinical symptoms after using elemene
for 1 or 2 courses of treatment. In some patients, imaging told the tumor stop growth,
and the symptoms were eased. However, there are also patients who did not show
any improvement after using elemene. We summarize the indications of elemene as:
(1) can be used conventionally in treating glioma patients, but must be uses
early. It must be used in combination with other treatment methods such as surgery,
radiotherapy and chemotherapy. For patients that did not show any improvement
or even growth of the tumor after 1 to 2 courses of treatment, combined therapy
is recommended. (2) elemene is suitable for treating patients who did not show
any improvement after conventional surgery, radiotherapy and chemotherapy. Especially
glioma patients who are not suitable for taking surgery, with recurrence and in
the late stage may try elemene.
For some intracranial
malignant tumors, elemene can treat them effectively; for some others, it did
not work. Why? We do not have a good explanation. Gliomas had complicated
classification and a number of pathological subtypes. The treatment effect is
determined by a variety of factors.
3.3 existing problems
(1) The sensitivity to different types of gliomas needs to be further explored.
(2) The
standardization of clinical use of elemene needs to be verified by research
centers. (3) The anti-tumor mechanisms and related basic research of elemene
must go further.
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