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ANTICANCER RESEARCH 24-. 303-310 (2004)
Impact of Complementary Mistletoe Extract
Treatment on Quality of Life in Breast, Ovarian
and Non-small Cell Lung Cancer Patients. A Prospective
Randomized Controlled Clinical Trial
B. K. PIAO
1
, Y. X. WANG
2
, G. R. XIE
3
, U. MANSMANN
4
, H. MATTHES
5
, J. BEUTH
6
and H. S. LIN
1
1
GuangAn Men Hospital, Beijing;
2
Liaoning Tumor Hospital, Shenyang;
3
Tianjin Tumor Hospital, Tianjin, China;
4
Universitat Heidelberg, Institut für
Medizinische Biometrie und Informatik, Heidelberg; '' Gemeinschaftskrankenhaus Havelhöhe, Berlin;
6
Institut zur wissenschaftlichen Evaluation naturheilkundlicher Verfahren Universität zu Köln, Köln, Germany
Abstract. Standardized aqueous mistletoe extracts have been
applied to cancer patients for several decades as complementary
medicine. A multicentric, randomized, open, prospective clinical
trial was conducted in three oncological centers in the People's
Republic of China in Bejing, Shenyang and Tianjin. Following
the guidelines of "Good Clinical Practice" (GCP) this study was
performed to get information on efficacy, safety and side-effects
of the standardized mistletoe extract (sME). Two hundred and
thirty-three patients with breast (n=68), ovarian (n = 71) and
non-small cell lung cancer (NSCLC; n=94) were enrolled into
this study. Two hundred and twenty-four patients fulfilled the
requirements for final analysis (n = 115 treated with sME
HEL1XOR® A; n = 109 comprising the control group being
treated with the approved immunomodulatingphytopharmacon
Lentinan). All patients were provided with standard tumor-
destructive treatment schedules and complementarity treated
with sME or Lentinan during chemotherapy according to
treatment protocol. Biometrically, the patients of the control and
sME treatment group were comparable regarding distribution,
clinical classification (WHO) and treatment protocols. Analysis
was performed according to the "Intention to treat principle".
Quality of life (QoL) was significantly (p<0.05) improved for
patients who were complementarily treated with sME, as
determined by the questionnaires FLIC (Functional Living
Index-Cancer), TCM (Traditional Chinese Medicine Index) and
the KPI (Karnofsky Performance Index) in comparison to the
Correspondence to: J. Beuth, Institut zur wissenschaftlichen
Evaluation naturheilkundlicher Verfahren Universität zu Köln,
Robert-Koch St., 10, 50931 Köln, Germany, e-mail: Josef.Beuth
@medizin.uni-koeln.de
Key Words: Mistletoe extract, cancer patients, quality of life,
randomized controlled trial.
control group. Additionally, the occurrence of adverse events
(AEs) was less frequent in the sME than in the control group
(total number of AEs 52 versus 90 and number of serious AEs
5 versus 10 in study and control group, most of them due to
chemotherapy). Only one serious AE was allocated to
complementary treatment in each group (1 angioedema in sME
group). All other side-effects of the sME (7 harmless local
inflammtory reactions at subcutaneous injection site, 4 cases
with fever) were self-limiting and did not demand therapeutic
intervention. This study showed that complementary treatment
with sME can beneficially reduce the side-effects of
chemotherapy in cancer patients and thus improve quality of life.
Aqueous extracts from mistletoe are widely used in
complementary cancer treatment as immunomodulating
agents (1). They were introduced into oncological treatment
by Rudolf Steiner around 1920 and there are many reports
on clinical efficacy (2). However, the evidence of these
results is controversial because of the problem of adequate
methodology in evaluating the efficacy of complementary
medicine (3).
The production of market-authorized mistletoe extracts
is standardized. The biochemical analysis of these drugs
shows that they contain different pharmacologically relevant
substances (4). There is a great body of data on the
biochemical and physiological effects of defined substances,
for example mistletoe lectins 1-3, viscotoxins, membrane
vesicles, polysaccharides (1,5).
Mistletoe extracts with defined amounts of mistletoe
lectin-1 (ML-1) yielded promising experimental and clinical
results ( 6-8 ). Recent research showed that the same can
be found with sME with a predominant content of ML-3
(9,10 ). However, randomized controlled trials of adequate
methodology to evaluate the clinical benefit of sME are still
missing though urgently needed ( 2 ).
0250-7005/2004 $2.00+.40
303
ANTICANCER RESEARCH 24-. 303-310 (2004)
Table 1. Patient flow chart: Number of patients with corresponding treatment and evaluation scheme.
Patients randomized 233
No measurable tumor and/or metastases 117 Measurable tumor and/or metastases 116
NSCLC
31
breast
45
ovarian 41 NSCLC 63
breast
23
ovarian 30
Helixor Lentinan Helixor Lentinan Helixor Lentinan Helixor Lentinan Helixor Lentinan Helixor Lentinan
17 14 23 22 21 20 31 32 12 11 14 16
w : n w :n w: n w : n w : n w : n w : n w : n w : n w: n w: n w : n
5:1 6:9 5:1 3: 1* 3:1* 6: 13 1: 1* 4: 1* 6:10 6:6 6:9 2: 2*
6:14 7:2 6:20 6:13 6: 11 7: 4 4:1* 6: 19 7:1 7:4 8:5 3: 2*
7:1 8:3 7:1 7: 7 7: 1 8: 1 5: 1 7: 9 8:1 8:1
6:5
8:1
8:1 12: 1 8: 8 9:2 6:25 8: 2
7: 4
7:1 9: 1
8:2
8:2
9: 1
n.e. n.e. n.e. n.e.
n.e.
1 1 2 1
4
K:17 K:14 K:23 K: 21 K: 20 K: 20 K: 29 K: 31 K:12 K:11 K:14 K: 11
T:17 T:14 T:23 T:20 T:20 T: 20 T:27 T: 31 T:12 T:11 T:14 T: 11
F:17 F:14 F:23 F: 21 F: 20 F: 19 F:29 F: 31 F:12 F:11 F:14 F: 11
E:16
E:14 E:18 E: 14 E:20 E:20 E:29 E:31 E:12 E:11 E:14 E: 11
Treatment scheme described in weeks (w:n): w = duration of medication in weeks : n = number of patients treated
* patients with s 4 weeks of treatment
n.e.: number of not evaluated patients
Number of patients, evaluated by: K: Karnofsky Index; T: TCM; F: FLIC; E: tumor evaluation.
Table 11. Total study population. Comparison of sex and tumor characteristics in treatment groups.
ALL
Helixor Lentinan total p-value
N=118 N=115 N=233
N % N % N %
center Beijing 22 18.6 24 20.9 46 19.7 0.709
Shenyang 64 54.2 65 56.5 129 55.4
Tianjin 32 27.1 26 22.6 58 24.9
sex male 27 22.9 24 20.9 51 21.9 0.753
female 91 77.1 91 79.1 182 78.1
PT 1 10 8.5 16 13.9 26 11.2 0.121
2 46 39.0 31 27.0 77 33.0
3 36 30.5 31 27.0 67 28.8
4 19 16.1 23 20.0 42 18.0
X 7 5.9 14 12.2 21 9.0
pN 0 51 43.2 43 37.4 94 40.3 0.325
1 19 16.1 18 15.7 37 15.9
2 33 28.0 27 23.5 60 25.8
3 9 7.6 16 13.9 25 10.7
X 6 5.1 11 9.6 17 7.3
M 0 73 61.9 75 65.2 148 63.5 0.683
1 45 38.1 40 34.8 85 36.5
304
Piao et al: Complementary Mistletoe Extract Treatment
Table III. Total study population. Demographic characteristics and general anamnesis.
ALL GROUP N NMISS MEAN SDEV MIN Ql MEDIAN Q3 MAX P-VALUE
age Helixor 118 0 52.6 9.4 31.0 46.0 50.0 61.0 70.0 0.618
Lentinan 115 0 51.7 10.1 25.0 45.0 51.0 59.0 70.0
total 233 0 52.2 9.7 25.0 45.0 51.0 60.0 70.0
weight Helixor 118 0 63.0 10.6 39.0 56.0 62.0 70.0 92.0 0.030
Lentinan 115 0 60.8 10.3 42.0 54.0 59.0 65.0 100.0
total 233 0 61.9 10.5 39.0 55.0 60.0 67.0 100.0
body mass Helixor 118 0 23.7 3.4 15.8 21.0 23.4 26.4 33.0 0.457
index Lentinan 115 0 23.3 3.3 16.5 20.8 22.9 25.5 32.0
total 233 0 23.5 3.4 15.8 20.8 23.4 25.8 33.0
Table IV. Functional Living Index-Cancer (FLIC).
Key Words
Abbreviated questions of FLIC
1
)
De
p
ression
2) Stress
3) Thoughts about the disease
4) Leisure-time activity
5) Nausea
6) General condition
1) Activity
8) Dismay of relatives
9) Despair
10) Job satisfaction
11) Comfort
12) Derealization
13) Influence of pain
14) Worry about tumor disease
15) Daily activity
16) Social connections
17) Nausea frequency
18) Fear for the future
19) Social connections
20) Pain
21) Trust in treatment
22) Appearance
Do you feel depressed and how often?
Are you able to handle daily stress?
How often do you think about your disease?
Are you able to enjoy leisure-time activity?
Does nausea influence your daily activity?
How do you feel today?
Do you feel well enough to perform activities in the house?
Indicate how your tumor disease influences your social surrounding
How often do you feel discouraged?
How often were you satisfied with your job?
How comfortable/uncomfortable do you feel today?
Have relatives been derealized recently?
How does pain influence your daily life?
How often has your tumor disease imposed a hardship on you?
How much housework are you able to do?
How often did you meet with those closest to you?
How often do you suffer from nausea?
How strong is the intensity of your fear for the future?
How often did you meet with friends?
How much of the pain was based on your tumor disease?
Do you trust in your treatment?
How is your appearance today?
Here we report on a prospectively randomized clinical
multicenter study to evaluate the impact of sME
administered complementarity to the standard treatment of
patients with breast, ovarian and non-small cell lung cancer
(NSCLC).
Patients and Methods
The informed consent was signed during the screening procedure.
From July 2000 until October 2001, a total of 233 patients
suffering from breast (n = 68), ovarian (n = 71) and non-small cell
lung cancer (NSCLC; n = 94) were enrolled into this randomized
controlled trial (RCT) (Table I). Out of these, 224 patients were
evaluated in the final analysis (115 in the study group, 109 in the
control group).
The vote of the ethics commission was received from the
Hospital Guan An Men, Research Institute of TCM, China.
Randomization was carried out by this study centre. A computer-
generated random list with varying block size was generated for
each participating center and cancer entity. Treatment centers
comprised: Guang An Men Hospital, Bejing; Liaoning Tumor
Hospital, Shenyang; Tianjin Tumor Hospital, Tianjin, China. All
are specialized in consensus-based tumor-destructive treatment
modalities (Table II).
The RCT was performed following the "Guidelines on Clinical
Trials for New Phytopharmaca" and "Good Clinical Practice" (GCP).
The study was not blinded. After histological diagnosis (in
accordance with the Medical Administration Authority, Ministry of
Health, People's Republic of China) all patients underwent
conventional chemotherapy including cyclophosphamide (C),
adriamycin (A), cisplatin (P), 5-fluorouracil (F), vinorelbine (V),
305
ANTICANCER RESEARCH 24-. 303-310 (2004)
Table V. Total study population. Karnofsky Performance Index evaluated as reduced, stable and increased.
ALL
Helixor
Lentinan
Total
strat.
N = 115
N=108
N=223
p-value
N
% N
% N
%
KPI Reduced 4 3.5 12 11.1 16 7.2 0.002
Stable 53 46.1 61 56.5 114 51.1
Increased 58
50.4 35
32.4 93
41.7
Table VI. Total study population. Comparison of scores for each Traditional Chinese Medicine Index (TCM) symptom.
TCM Criteria Missing value
Remarkable
Improvement
Improvement Deterioration Stable
HELIXOR Lentinan HELIXOR Lentinan HELIXOR Lentinan HELIXOR Lentinan HELIXOR Lentinan
N N / % N / % N / % N / % N / % N / % N / % N / %
General
0 1
0
2
1 1
0 1
1 1
7
(6.1 %)
2
(1.8 %)
37
(32.5 %)
30
(27.5 %)
6
(5.3 %)
17
(15.6 %)
65
(56.1 % )
61
(55.0 %)
11
fatigue
Insomnia
Anorexia
Nausea
Pain
(9.6 %)
2
(1.9 %)
21
(18.4 %)
18
(16.7 %)
4
(2.6 %)
9
(9.3 %)
79
(69.3 %)
78
(72.2 %)
10
(8.8 %)
4
(3.7 %)
31
(27.4 %)
19
(17.4 %)
12
(10.6 %)
27
(24.8 %)
61
(53.1 %)
58
(54.1 %)
2
(1.8%)
0
(0%)
18
(15.8 %)
6
(5.5 %)
(11.4%)
14
(26.6 %)
28
(71.1 %)
8174
(67.9 %)
5
(4.4 %)
19
(17.4 %)
18
(15.9 %)
5
(4.6 %)
3
(2.7 %)
8
(7.3 %)
88
(77.0 %)
76
(70.6 %)
Remarkable improvement means improvement in at least two steps: from "middle" to "none", from "serious" to "slight" or "none".
Improvement means improvement in one step: from "slight" to none, from "middle" to "slight", from "serious" to "middle".
mitomycine (M), ifosfamide (I), vindesine (Vi), or carboplatin (cP);
breast cancer: CAP, CAF; ovarian cancer: CP, IcP; NSCLC: VP,
MViP. After randomization, patients of the study group were
complementarily treated with the standardized mistletoe extract
HELIXOR® A (sME; Helixor Heilmittel GmbH & Co. KG,
Rosenfeld, FRG), subcutaneously, 3 times per week, with escalating
dosages starting with 1 mg up to a maximum dose of 200 mg
independently from the chemotherapy schedule. Patients of the
control group were treated with the authority approved
phytopharmacon Lentinan, intramuscularly, 4 mg per injection, daily.
Lentinan, a phytotherapeutic agent, belongs to the national second
class of new phytopharmaca (Authorization No. 92 Z-61 for Drugs;
Ministry of Health) and is a protected preparation. Lentinan, a
purified polysaccharide, is a biological response modifier and its
antitumor activity is mediated by the augmentation of the activity of
NK-cells, macrophages and cytotoxic T-lymphocytes. Lentinan is
regularly used with Tegafur (a prodrug of 5-FU) and is considered to
prolong survival and improve quality of life (QoL) in combination
with other chemotherapeutic agents (12 ).
Study and control groups of patients were demographically
comparable, especially concerning tumor entity, stage and
conventional treatment (Tables II and III). Inclusion (exclusion)
criteria were fixed, followed international standards and mainly
comprised: histologically verified breast, ovarian and NSCL
cancers; indication for chemotherapy, however, no tumor-
destructive treatments applied during the previous month; age 18-
70 years; KPI >50%; survival expectancy > 3 months; hospital
bound patients; no additional immunomodulating therapy.
There were 9 patients in whom it was not possible to take
measurements of the endpoints of interest (Table I, Patients with
<4 weeks of treatment were not evaluated for QoL because of the
short observation period). These 9 patients were excluded from the
analysis, because there is no methodologically acceptable way to
impute the missing observations for an analysis of the total set of
patients enrolled in the study.
Quality of life (QoL) measurement. QoL was evaluated regularly by
the internationally approved questionnaires FLIC (Functional Living
Index-Cancer) (Table IV), TCM (Traditional Chinese Medicine
Index) comprising nausea, vomiting, fatigue, insomnia, anorexia and
the KPI (Karnofsky Performance Index). QoL evaluation was
performed "at screening" as well as at the end of the treatment.
306
Piao et al: Complementary Mistletoe Extract Treatment
Table VII. Total study population. Difference of Traditional Chinese Medicine Index (TCM) total score between screening and final investigation.
ALL GROUP N NMISS MEAN SDEV M1N MEDIAN MAX strat. p-value
TCM
score
Helixor
Lentinan
total
113
107
220
2
2
4
-1.3
-0.2
-0.8
2.4
2.3
2.5
-8.0
-6.0
-8.0
-1.0
0.0
0.0
5.0
6.0
6.0
0.0007
Table VIII.Tolal study population. Difference of Functional Living Index-Cancer (FLIC) between screening and final investigation.
ALL GROUP N NMISS MEAN SDEV MIN MEDIAN MAX strat.p-value
FLIC score
Helixor
Lentinan
Total
115
107
222
0
2
2
9.0
4.7
6.9
16.6
17.5
17.1
-32.0
-32.0
-32.0
6.0
3.0
4.5
56.0
89.0
89.0
0.0141
Safety. Evaluation of safety of the treatment with the sME
consisted of analysis of the number and severity of adverse events
(AEs), the duration, treatment, outcome and the causes of AEs
(chemotherapy, sME, Lentinan, basic disease or others).
Statistics. Statistical analysis was performed using SAS Version 8.02
and StatExact Version 5. Analysing the trial population and
describing the efficacy criteria, safety criteria and quality of life
questionnaires at baseline and at final end of treatment, binary and
categorical data were evaluated with Fisher's exact test, while
continuous data were compared by means of Wilcoxon-Mann-
Whitney test (University of Heidelberg, Germany, Institute of
Medical Biometry and Informatics).
Results
The influence of standardized mistletoe extract (sME)
HELIXOR® A treatment on side-effects and toxicity of
chemotherapy correlating to QoL can be reproducibly
evaluated by standardized questionnaires, for example FLIC
and TCM Index as well as the KPI Index. Thus, these
questionnaires were determined before and after
chemotherapeutic treatment of breast, ovarian and NSCL
cancer patients.
The Karnofsky Performance Index (KPI) evaluates the
physical conditions of patients and classifies them as
reduced, stable or increased. In total 223 patients could be
evaluated (sME group n = 115; control group n = 108)
(Tables I and V). As shown in Table V, patients
complementarity treated with sME presented an increased
KPI in 50.4 % (32.4 % in the control group) and a reduced
KPI in 3.5 % (11.1 % in the control group; Table V). The
KPI improvement of the study group was statistically
significant as compared to the control group (p = 0.002)
(Figure 1).
According to TCM, various symptoms were evaluated by
scoring. As shown in Tables I and VII a total of 220 patients
could be evaluated (sME group n = 113; control group
n=107). Concerning nausea, fatigue, insomnia and anorexia,
more patients improved and fewer patients deteriorated in the
study group as compared to the control group (Table VI,
Figure 1). However, the difference in the overall TCM score
between the beginning and termination of the tumor-
destructive chemotherapy demonstrates a statistically
significant improvement of the quality of life in the sME study
group (p = 0.0007) as compared to the control group (Table
VII). The TCM score consists of the sum of five symptoms;
each symptom is quantified with four levels reaching from 0
to 3 and a higher level expresses higher severity in the
symptom. Therefore, an improvement in TCM comparing
baseline and final examination results in a negative number.
A change of -1 describes an improvement by one level in the
total TCM score and may be interpreted as the improvement
in one single symptom of one level while no change in severity
happens in the three remaining symptoms.
The Functional Living Index-Cancer (FLIC) consists of
22 questions on physical, psychological and social well
being, nausea and pain (Table IV). As shown in Table I and
VIII a total of 222 patients could be evaluated (sME group
n=115; control group n = 107). The global FLIC score
demonstrated a significant improvement (p=0.0141) of QoL
for patients of the sME study group as compared to those
of the control group (TableVIII). Especially the symptoms
of nausea and pain presented significant improvements for
patients of the study group (results not shown).
The total number of adverse events (AEs) was 52 in the
sME study group and 90 in the Lentinan control group
(serious AEs: 5 versus 10) (Figure 2). Chemotherapy-related
AEs were 28 for the sME and 77 for the Lentinan group.
307
ANTICANCER RESEARCH 24-. 303-310 (2004)
General Results / Quality of Life
8 Helixor ® ■ Lentinan
50.4%
Adverse and Serious Adverse Events
= 90
Figure 1. Improvement of quality of life evaluated by KP1-, FLIC-and
TCM-indices.
Figure 2. Adverse events (AEs)and serious adverse events of the sME and
Lentinan group. The majority of AEs in both groups was due to
chemotherapy, and the HELIXOR® group significantly gained by
reduction of chemotherapy-related events.
Each symptom of an adverse event was classified as one AE,
for example nausea and vomiting following standard
chemotherapy were registered as two AEs, despite being
pathogenetically closely related. If all simultaneously
occurring and closely related symptoms were registered as
one patient-related AE, the total number of AEs and SAEs
would drop from 52 to 32 for the study group and from 90
to 59 for the control group, respectively. However, the
relationship of AEs and SAEs between the study and
control group would be unchanged.
In the therapy as well as in the control group only one
serious AE was allocated to complementary treatment on
account of hospitalization. In the study group one patient
responded to the sME application with angioedema and
urticaria. After discontinuation of the sME administration
and anti-allergic treatment, the patient recovered from
angioedema within 2 days, however, skin reactions remained
for about 7 days. All other side-effects of sME (fever in 4
patients, rubor/pruritus at the injection site in 7 patients)
were harmless, self-limiting and did not warrant
therapeutical intervention. Also, in the control group, one
serious AE occurred which was allocated to the
phytopharmacon Lentinan. All other cases of serious AEs
were allocated to chemotherapy or to the basic disease.
Thus, sME appears to be a safe and well tolerated drug.
Discussion
Previous clinical investigations have shown that
complementary application of aqueous standardized
mistletoe extracts (sME) can relevantly reduce the side-
effects of standard tumor-destructive chemo7radiotherapies
(6-8,11). On the basis of pharmacological,
pharmacokinetical and pharmatoxicological investigations,
an approval for the conduction of a clinical trial for
imported drugs (sME; HELIXOR® A) was officially given
by the Authority for Drug Surveillance and Administration,
People's Republic of China (Application No. A960162;
Authorization No. ZL 2000001). This randomized
controlled trial (RCT) was carried out following the
"Guidelines on Clinical Trials for New Phytopharmaca" and
"Good Clinical Practice" (GCP) to evaluate efficacy, safety
and side-effects of sME. In three oncological centers
(Bejing, Shenyang, Tianjin) breast, ovarian and NSCL
cancer patients were randomized into a study group
(standard chemotherapy and complementary sME
application) and control group (standard chemotherapy and
Lentinan injection).
Biometrically, patients of the study and control groups
were comparable with respect to age, clinical classification
(WHO) and treatment protocols. Accordingly, a valid
conclusion concerning primary study goals (safety of sME
administration, influence on side-effects of tumor-
destructive therapies, quality of life) can be drawn.
Evaluation of recurrence-free, metastasis-free and overall
survival is not useful because of the limited follow-up time
as well as the short treatment period with sME.
Usually most of the patients receiving sME develop a
distinct local inflammatory skin reaction at the
subcutaneous injection site. This kind of reaction usually
does not occur after intramuscular Lentinan application. In
case of subcutaneous injection of placebo (such as
physiological saline), this reaction does not occur, either.
Thus, blinding was not possible in this clinical trial because
308
Piao et al: Complementary Mistletoe Extract Treatment
most of the patients as well as clinicians would have
recognized whether sME, Lentinan or placebo was applied
after a short treatment period.
For many drugs, except most anticancer chemotherapeutical
substances, placebos make blinding possible by helping to
control measurement bias when accessing the outcome of a
trial. It may be hypothesized that differences in the information
provided to patients may be responsible for differences in the
outcome (for example QoL) of this trial. However, patients
allocated to the control group received Lentinan, which is a
well known immunmodulating drug in China and Japan;
therefore the risk of getting an information bias as well as
seeking treatment (HELIXOR®) outside the trial is very low.
Far fewer AEs were recorded in the sME study group
than in the control group (Figure 2). Altogether 5 serious
AEs in the sME study group and 10 serious AEs in the
Lentinan control group were registered; only one serious
AE in each group was allocated either to sME or to
Lentinan. All other side-effects of sME (fever, rubor and
pruritus at the injection site) were harmless, self-limiting
and did not afford therapeutical intervention. Thus, sME
treatment was regarded as safe.
Twenty-eight AEs in the HELIXOR® group were related
to chemotherapy in comparison to 77 AEs in the Lentinan
group. Since most of the AEs were related to chemotherapy,
the definitely lower number and severity of AEs within the
study group points to a more beneficial effect of sME on
tolerance of chemotherapy, as compared to the control
group. This is in accordance with a significant improvement
of QoL which was demonstrated concurrently by the
standard questionnaires (FLIC, TCM) as well as the KPI
Index for the patients of the sME study group as compared
to those of the control group (Figure 1).
This RCT demonstrated a biometrically significant
benefit for the patients of the study group (complementarity
treated with sME) as compared to the control group
(treated with the China-approved phytopharmacon
Lentinan) under tumor-destructive chemotherapy. The
significant results of the HELIXOR® group may be much
better interpreted in the light of the proven beneficial
effects of Lentinan (control group) in previous studies (12).
However, further studies on defined tumor entities and
stages (after precise stratification) and appropriate numbers
of patients are needed to prove the clinical efficacy of sME
in cancer parients.The actual RCT was an approval study
for the People's Republic of China and obviously
demonstrates the beneficial effect of complementary sME
application during tumor-destructive chemotherapy.
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Received May 27, 2003
Revised September 12, 2003
Accepted December 19, 2003
309
