Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study. Prospective controlled cohort studies on long-term therapy of ovairian cancer patients with mistletoe (Viscum album L.) extracts iscador. Mistletoe treatment induces GM-CSF- and IL-5 production by PBMC and increases blood granulocyte- and eosinophil counts: a placebo controlled randomized study in healthy subjects. 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. Adjuvant intravesical treatment of superficial bladder cancer with a standardized mistletoe extract. Influence of complementary Viscum album (Iscador) administration on microcirculation and immune system of ear, nose and throat carcinoma patients treated with radiation and chemotherapy. Immunologic Effector Mechanisms of a Standardized Mistletoe Extract on the Function of Human Monocytes and Lymphocytes in vitro, ex vivo, and in vivo Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial. In vivo-induction of antibodies to mistletoe lectin-1 and viscotoxin by exposure to aqueous mistletoe extracts: a randomised double-blinded placebo controlled phase I study in healthy individuals. [Iscador QuS and human recombinant interferon alpha (Intron A) in cervical intraepithelial neoplasia (CIN)]. The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial. Randomised and non-randomised prospective controlled cohort studies in matched-pair design for the long-term therapy of breast cancer patients with a mistletoe preparation (Iscador): a re-analysis. The standardised mistletoe extract PS76A2 improves QoL in patients with breast cancer receiving adjuvant CMF chemotherapy: a randomised, placebo-controlled, double-blind, multicentre clinical trial. [Role of immunomodulatory treatment with Iscador QuS and Intron A of women with CIN1 with concurrent HPV infection]. The influence of isorel on the advanced colorectal cancer. Prospective Controlled Cohort Studies on Long-Term Therapy of Breast Cancer Patients with a Mistletoe Preparation (Iscador®) Reporting Randomized, Controlled Trials of Herbal Interventions: An Elaborated CONSORT Statement Cellular immunomodulation and safety of standardized aqueous mistletoe extract PS76A2 in tumor patients treated for 48 weeks. External validity of randomised controlled trials: “To whom do the results of this trial apply?” Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial. Immunoprotective activity of the galactoside-specific lectin from mistletoe after tumor destructive therapy in glioma patients. Mistletoe treatment for cancer review of controlled trials in humans. Matched-pair study showed higher quality of placebo-controlled trials in Western phytotherapy than conventional medicine. Weekly 24 h infusion of aviscumine (rViscumin): a phase I study in patients with solid tumours. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials
CONTEXT In anthroposophical medicine , total extracts of Viscum album ( mistletoe ) have been developed to treat cancer patients . The oldest such product is Iscador . Although Iscador is regarded as a complementary cancer therapy , it is the most commonly used oncological drug in Germany . OBJECTIVE To determine whether Iscador treatment prolongs survival time of patients with carcinoma of the colon , rectum , or stomach ; breast carcinoma with or without axillary or remote metastases ; or small cell or non-small-cell bronchogenic carcinoma ; and to explore synergies between Iscador treatment and psychosomatic self-regulation . DESIGN Prospect i ve nonr and omized and r and omized matched-pair studies nested within a cohort study . SETTING General community in Germany . PARTICIPANTS 10,226 cancer patients involved in a prospect i ve long-term epidemiological cohort study , including 1668 patients treated with Iscador and 8475 who had taken neither Iscador nor any other mistletoe product ( control patients ) . INTERVENTION Iscador . MAIN OUTCOME MEASURE Survival time . RESULTS In the nonr and omized matched-pair study , survival time of patients treated with Iscador was longer for all types of cancer studied . In the pool of 396 matched pairs , mean survival time in the Iscador groups ( 4.23 years ) was roughly 40 % longer than in the control groups ( 3.05 years ; P < .001 ) . Synergies between Iscador treatment and self-regulation manifested in a longer survival advantage for Iscador patients with good self-regulation ( 56 % relative to control group ; P = .03 ) than for patients with poor self-regulation . Results of the 2 r and omized matched-pair studies largely confirmed the results of the non-r and omized studies . CONCLUSION Iscador treatment can achieve a clinical ly relevant prolongation of survival time of cancer patients and appears to stimulate self-regulation BACKGROUND Mistletoe extracts such as Iscador are commonly used as complementary/anthroposophic medications for many cancer indications , particularly for solid cancers . The efficacy of this complementary therapy is still controversial . OBJECTIVE Does long-term therapy with mistletoe extracts Iscador show any effect on survival and psychosomatic self-regulation of patients with ovarian cancer ? PATIENTS AND METHODS Prospect i ve recruitment and long-term follow-up in controlled cohort studies . ( 1 ) Two r and omized matched-pair studies : OvarR and ( ovarian cancer patients without distant metastases ; 21 pairs ) and OvarMetR and ( ovarian cancer patients with distant metastases ; 20 pairs ) ; patients having no mistletoe therapy were matched for prognostic factors . By paired r and om allocation , one of the patients of each pair was suggested therapy with mistletoe extracts Iscador to be applied by her attending physician . ( 2 ) Two non-r and omized matched-pair studies : Ovar ( ovarian cancer patients without distant metastases ; 75 pairs ) and OvarR and ( ovarian cancer patients with distant metastases ; 62 pairs ) ; patients that already received therapy with mistletoe extracts Iscador were matched by the same criteria to control patients without therapy with mistletoe extracts Iscador . RESULTS For overall survival in the r and omized studies , the effect in favor of therapy with mistletoe extracts Iscador was significant in OvarMetR and but not in OvarR and ; hazard ratio estimate and 95 % confidence interval : 0.40 ( 0.15 , 1.03 ) and 0.33 ( 0.12 , 0.92 ) , respectively . In the non-r and omized studies Ovar and OvarMet , the results adjusted for relevant prognostic variables were 0.47 ( 0.31 , 0.69 ) and 0.62 ( 0.37 , 1.05 ) . Psychosomatic self-regulation in the Iscador group increases significantly within 12 months on a scale from 1 to 6 compared with the control group in the r and omized study OvarR and as well as in the non-r and omized study Ovar on patients with ovarian cancer without distant metastases ; estimate of the median difference and 95 % confidence interval : 0.58 ( 0.30 , 0.90 ) and 0.30 ( 0.05 , 0.65 ) , respectively . CONCLUSION Mistletoe extracts Iscador might have the effect of prolonging overall survival of ovarian cancer patients . In the short term , psychosomatic self-regulation increases more markedly under Iscador therapy than under conventional therapy alone OBJECTIVE Various immunological effects have been reported during application of mistletoe preparations . Because these data are heterogeneous , we performed a placebo controlled study to investigate ( 1 ) effects on peripheral granulocyte and eosinophil counts , ( 2 ) related cytokine levels and ( 3 ) whether effects are related to mistletoe lectin ( ML ) . METHODS 43 volunteers were r and omized to receive the mistletoe plant extract Iscador Quercus spezial ( IQ ) , purified ML , IQ which was depleted from ML , or placebo subcutaneously twice per week for 8 weeks . Weekly , differential blood count and every four weeks spontaneous and IQ- and ML-induced cytokine production by peripheral blood mononuclear cells ( P BMC ) were analyzed . RESULTS Leukocyte- , granulocyte- , and eosinophil counts were significantly higher during treatment in the IQ- and ML-groups than in the placebo group . Furthermore , a significant increase of antigen-induced production of GM-CSF , IL-5 and IFNgamma by P BMC was observed in the IQ- and ML-group but not in the groups receiving ML-depleted IQ or placebo .  Severe side effects did not occur in any of the subjects . CONCLUSIONS Treatment with IQ or ML stimulates the production of GM-CSF , IL-5 and IFNgamma by P BMC , and this is accompanied by an increase of eosinophil- and granulocyte-counts . These observations may , therefore , open rational therapeutic indications for mistletoe extracts St and ardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine . A multicentric , r and omized , open , prospect i ve 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 st and ardized 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 HELIXOR A ; n=109 comprising the control group being treated with the approved immunomodulating phytopharmacon Lentinan ) . All patients were provided with st and ard tumor-destructive treatment schedules and complementarily 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 protocol s. 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 question naires FLIC ( Functional Living Index-Cancer ) , TCM ( Traditional Chinese Medicine Index ) and the KPI ( Karnofsky Performance Index ) in comparison to the 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 inflammatory reactions at subcutaneous injection site , 4 cases with fever ) were self-limiting and did not dem and 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 PURPOSE Adjuvant intravesical immunotherapy with bacillus Calmette-Guerin ( BCG ) for noninvasive superficial bladder cancer has been shown to decrease tumor recurrence significantly . However , serious local and systemic side effects of this treatment have promoted the use of other immunoactive substances , which to date have failed to show efficacy equal to that of BCG immunotherapy . MATERIAL S AND METHODS In the current phase I/II clinical trial an aqueous mistletoe extract st and ardized to mistletoe lectin was administered intravesically to 30 patients with superficial urothelial bladder carcinoma . About 4 weeks after transurethral resection each patient received 6 instillations at weekly intervals of 50 ml extract with mistletoe lectin concentrations between 10 and 5,000 ng/ml , which was retained in the bladder for 2 hours . Three patients per group received a dose , which was then doubled in the next group . Clinical followup consisted of examinations with cystoscopy , cytology and r and om biopsies . To detect cytokines and tumor necrosis factor-p75 receptor venous blood and urine sample s were taken before instillation , and 2 , 6 and 24 hours thereafter . RESULTS The tolerability of intravesically administered mistletoe extract was good at all applied concentrations . None of the patients had local or systemic side effects according to WHO classification 1 - 4 . Within the 12-month observation time study patients with pTa G2 and pT1 G2 tumors showed a recurrence rate of 33 % , comparable to that in a local historical control group of patients with equal stage and grade who were treated with adjuvant BCG . Comparison of urine cytokine levels before instillation , and 2 , 6 and 24 hours thereafter brought about no significant alterations in all measured cytokines . CONCLUSIONS From these results it is concluded that st and ardized mistletoe extract could be a potential alternative adjuvant therapy for superficial bladder cancer . Nevertheless , the optimal intravesical treatment regimen has yet to be defined With the techniques of vital microscopic and reflection spectrometric imaging , representative characteristics of microcirculation and immunology of white blood cells were evaluated before , during and after  radiotherapy and chemotherapy of patients suffering from ear , nose and throat carcinomas .  Adverse effects of radiotherapy and chemotherapy on the microcirculation and the immune system were decreased and reconstitution processes were accelerated by complementary administration of a st and ardized mistletoe extract ( Iscador ) Even though mistletoe extracts have been in clinical use for centuries their exact mode of action is still unknown . Currently , the application scheme for registered preparations is a dose-escalating scheme to thus reduce side effects . In this study , healthy controls and patients were evaluated for their immunologic response to treatment with a st and ardized mistletoe extract ( Iscador ) . It shows a strong effect as adjuvant that induces TNF-α and IL-12 , which was partly mediated via CD14 . Desensitization of the TNF-α response could be shown after repeated application in vitro and in vivo . Furthermore , Iscador induces a specific lymphocyte sensitization upon multiple injections and production of IgG1- and IgG3-mistletoe antibodies . Remarkably , a systemic byst and er effect ( heterologous immunity against other recall antigens ) was observed after long-term treatment . In conclusion , dose-escalation reduces the monocyte-related clinical side effects . A T-lymphocyte sensitization stimulates mainly a specific Th1 response . The most interesting clinical long-term effect is the byst and er stimulation of various memory T cells that might mediate in vivo antitumor and antiinfectious T-cell response under mistletoe-extract immunization Malignant glioma patients were prospect ively enrolled into a clinical trial . All the patients were provided with the internationally recommended oncologic st and ard treatment ( neurosurgery , radiation , basic clinical care according to protocol and indication ) and r and omly divided into a treatment group ( receiving complementary immunotherapy with a galactoside-specific lectin from mistletoe , ML-1 ) and a control group ( without additional complementary treatment ) . Whereas the beneficial effects of ML-1 treatment on immunological rescue and quality of life have been recently shown , evaluation of relapse free/overall survival was performed after a 50 months follow up time . Non-stratified analysis of all the patients revealed non-relevant prolongation of relapse-free intervals/overall survival time for the treatment group . However , analysis of stratified stage III/IV glioma patients demonstrated : 1 . a tendency for a prolongation of relapse-free survival for patients of the treatment group ( 17.43 + /- 8.2 months ) vs. the control group ( 10.45 + /- 3.9 months ) 2 . a statistically significant ( BRESLOW p = 0.035 ) prolongation of the overall survival for the treatment group ( 20.05 + /- 3.5 months ) as compared to the control group ( 9.90 + /- 2.1 months ) . These promising data warrant confirmation in a GCP-based prospect ively r and omized ( multicenter ) study , which is currently under consideration Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists The objective of this r and omised , multicentre , double-blind clinical trial was to investigate the impact of PS76A2 , an aqueous mistletoe extract st and ardised to mistletoe lectins , on quality of life ( QoL ) in breast cancer patients . A total of 352 patients were r and omly allocated to 2 groups receiving PS76A2 ( 15 ng mistletoe lectin/0.5 ml ) or matching placebo twice weekly for 4 to 6 cycles of CMF ( cyclophosphamide , methotrexate , fluorouracil ) chemotherapy followed by 2 months follow-up . The primary efficacy end-point was the change from baseline of 3 FACT-G subscales ( physical , emotional and functional well-being ) during the fourth CMF cycle . Secondary measures included GLQ-8 ( 8 linear analogue self- assessment scales ) , Spitzer 's uniscale and haematological variables . The main variables of safety analysis were adverse events , including injection site reactions and clinical laboratory tests . The results showed that physical , emotional and functional well-being improved upon PS76A2 , but deteriorated following placebo . The treatment differences were statistically significant for the 3 subscales as well as for the summary score FACT-G , which was analysed as O'Brien 's rank sum of its 3 subscales : The total score increased by 4.40 + /- 11.28 , indicating a higher QoL after PS76A2 , but decreased by 5.11 + /- 11.77 with placebo ( p<0.0001 ) . The GLQ-8 sum of 8 LASA scales was analysed as a summary score of GLQ-5 ( sum of item nos. 1 , 5 , 6 , 7 , 8) and GLQ-3 ( sum of item nos. 2 , 3 , 4 ) . GLQ-5 characterises typical aspects of QoL , while GLQ-3 consists of 3 side-effects of CMF ( feeling sick , numbness or pins and needles , loss of hair ) . GLQ-5 decreased by 42.9 + /- 125.0 upon PS76A2 , indicating an improvement in QoL , but increased by 60.3 + /- 94.0 upon placebo ( p<0.0001 ) . GLQ-3 deteriorated in both groups ( PS76A2 : 13.9 + /- 52.4 ; placebo : 34.5 + /- 57.0 ) , but the differences in favour of PS76A2 were , nevertheless , statistically significant ( p=0.0007 ) . The total score GLQ-8 improved by 28.9 + /- 154.6 after PS76A2 and deteriorated by 94.8 + /- 141.1 after placebo ( p<0.0001 ) . Spitzer 's uniscale improved by 12.2 + /- 30.7 upon PS76A2 and deteriorated by 10.8 + /- 26.1 with placebo ( p<0.0001 ) . After follow-up without chemotherapy , a significant treatment difference in favour of PS76A2 was determined by means of FACT-G , GLQ-8 and Spitzer 's uniscale . PS76A2 was well tolerated in this trial , with the exception of slight local reactions in 17.6 % of the PS76A2 group . In conclusion , PS76A2 ( 15 ng mistletoe lectin/0.5 ml twice weekly ) was shown to be safe and effective in improving QoL in breast cancer patients during chemotherapy and follow-up BACKGROUND Several studies have been performed in tumour patients to analyse the immunological response to mistletoe extracts . Considering the fact that these extracts are given subcutaneously in most instances , the kind of application resembles a typical immunization schedule . We therefore wanted to see how those extracts act on immunocompetent cells of healthy individuals hoping that this kind of provocation test may give new informations about a more specific application of these extracts in certain diseases . SUBJECTS/ METHODS 47 healthy individuals were exposed for twelve weeks either to Iscador Quercus special ( IQ )  known to be rich in mistletoe lectin (ML)-1 ( n = 16 ) , to Iscador Pini ( IP ) being poor in ML-1 but enriched in viscotoxins ( n = 15 ) , or to  placebo ( physiological saline )  ( n = 16 ) in a r and omised , double-blinded placebo-controlled study . Humoral immunoreactivity was analysed by measuring antibodies towards the two compounds ML-1 and viscotoxin VA2 ( VA2 ) . Sera were collected in intervals of four weeks up to week 12 and again three months after last exposure . RESULTS None of the subjects had antibodies to ML-1 or VA2 before exposure . In week 12 , anti-ML-1 antibodies of the IgG-type were found in all 16 IQ-treated individuals but only 6 of the 15 prob and s exposed to IP . In contrast , anti-VA2 IgG-antibodies could be detected in all individuals of both groups . The antibodies were preferentially of the IgG1 and IgG3 type while antibodies of the IgA and IgM type were produced only in a few prob and s. Antibodies of the IgE-type occurred only in the IQ-exposed individuals and were directed against ML-1 but not VA2 . None of the prob and s receiving placebo developed antibodies to ML-1 or VA2 . Severe side effects were not observed in any of the prob and s. CONCLUSIONS These data obtained in healthy individuals clearly indicate that IQ and IP-extracts can induce antigen-specific humoral responses . They may , therefore , provide , a solid basic for the evaluation of the humoral immune response in disease states For several years there has been the association between the persistent HPV infection ( especially with high oncogenic potency i.e. 16 , 18 ) and the cervical intraepithelial neoplasia . The pathomechanism is probably considered with spread of the early virus gene E1 , E2 and the suppressor protein p53 complexes . Further on these complexes cause the neoplastic cell transformation . There has also been described the role of impaired immune response in these cases . The abnormalities cover malformation of antigen presenting system APC , decrease of MHC-I and MHC-II heavy chains rate , decrease of the Langer-hans cells and decrease of count and cytotoxic activities of lymphocytes B and NK cells . The invasive and destructive techniques of HPV associated CIN treatment do not respect its pathogenesis . Therefore the new non surgical methods of treatment would play a major role in treatment and prevention of women especially in their reproductive period . The aim of this work was the evaluation of the Iscador QuS and Intron A role in the management of HPV associated CIN . The 60 patients with CIN and HPV have been diagnosed and treated in our clinic for 12 months . Early results present increase of regression and significant decrease of progression rates in both groups of examined women , comparing to the control group . The stationery state rates in this groups of women were similar to the control group The effect of an adjuvant mistletoe extract treatment was tested in a prospect i ve , r and omised controlled clinical trial involving 477 patients with head and neck squamous cell carcinoma . The patients were stratified into two treatment groups that underwent surgery or surgery followed by radiotherapy and both groups were r and omised for additional treatment with mistletoe extract . Patients treated with a mistletoe lectin-1 ( ML-1 ) st and ardised mistletoe preparation had no lower risk of local/locoregional recurrences , distant metastases or second primaries . In the main analysis based on 202 patients treated with surgery and 275 patients treated with surgery and radiotherapy the adjusted hazard ratio for the disease-free survival ( DFS ) was 0.959 ( 95 % confidence interval ( CI ) 0.725 - 1.268 ) . The 5-year survival rates of patients from the mistletoe group were no better than the survival rates of patients from the control group . Furthermore , no significant changes in the cellular immune reaction or in quality of life could be detected . We conclude that the used mistletoe preparation has no indication in the adjuvant treatment of patients with head and neck cancer OBJECTIVE Exp and ed presentation and re- analysis of previously published data of r and omized and non-r and omized studies on mistletoe therapy with breast cancer patients [ 3 , 4 ] . The main question is : Does a re- analysis confirm the previously reported effects of prolonging the survival of patients with breast cancer under long-term application of a complementary/anthroposophic therapy with the European mistletoe preparation Iscador ? DATA SOURCES ( 1 ) R and omised matched-pairs study : Breast cancer patients with only lymphatic metastases ( 17 pairs ) that had never used mistletoe therapy  were matched for several prognostic factors . By paired r and om allocation , one patient of a pair received a suggestion of mistletoe therapy to be applied by the attending physician . ( 2 ) Non-r and omised matched-pairs studies : Patients that had already received mistletoe ( Iscador ) therapy  were matched to control patients from the same pool using the same prognostic criteria . Three groups were recruited by this procedure : breast cancer with local recurrences and no metastases ( 42 pairs ) , breast cancer with only lymphatic metastases ( 55 pairs ) , and breast cancer with distant metastases ( 83 pairs ) . ANALYSIS Cox proportional hazard models and sensitivity analyses based on subsets of the original data sets according to strict or lose application of the matching criteria . RESULTS The results of this re- analysis are consistent with the earlier results , even when comparing different methods and subsets . In the r and omised study , the effect of long-term Iscador therapy on overall survival is significantly in favour of the Iscador therapy : Estimate of the median difference and 95 % confidence interval in years 2.5 ( 0.83 , 4.50 ) . The results for the non-r and omised studies were also in favour of the Iscador therapy : Breast cancer with local recurrences and no metastases : estimate of hazard ratio and 95 % confidence interval 0.52 ( 0.23 , 1.17 ) ; breast cancer with lymphatic metastases : 0.27 ( 0.15 , 0.50 ) ; breast cancer with distant metastases : 0.53 ( 0.32 , 0.88 ) . As a short-term effect of this therapy , psychosomatic self-regulation noticeably increases within 3 months in the Iscador group in comparison to the control group in the r and omised study : estimate of the median difference 0.90 ( 0 , 1.75 ) . CONCLUSION The re- analysis demonstrates that the effects shown in the previously published data are consistent despite using different analytic methods and different subsets . Overall , the survival of patients receiving mistletoe treatment with Iscador  is longer in these studies . In the short term , psychosomatic self-regulation , as a measure of autonomous coping with the disease , rises more under Iscador therapy than under conventional therapy alone Patients with breast cancer receiving adjuvant chemotherapy  frequently suffer from a restricted quality of life ( QoL ) due to the side-effects of chemotherapy and the consequences of coping with the diagnosis . Therefore , the objective of this clinical study was to investigate the impact of PS76A2 , an aqueous mistletoe extract st and ardised to the galactoside-specific mistletoe lectin , on QoL by performing a placebo-controlled trial . Overall , 272 patients with breast cancer receiving adjuvant CMF chemotherapy ( cyclophosphamide-methotrexate-fluorouracil )  were enrolled and r and omised to groups receiving placebo or PS76A2 at concentrations of 10 , 30 or 70 ng mistletoe lectin ( ML ) per ml . The patients received 0.5 ml study medication twice weekly subcutaneously for 15 consecutive weeks ( 4 CMF cycles ) . Primary variables were the self- assessment QoL scores GLQ-8 ( Global Life Quality ) and Spitzer 's uniscale . As a result , statistically significant effects on QoL were obtained with the medium dose ( 15 ng ML/0.5 ml ) . The treatment difference between the medium dose and placebo with regard to the GLQ-8 sum was 60.8 mm ( 95 % confidence interval : 19.3 to 102.0 mm ) . The treatment effect for Spitzer 's uniscale between the medium dose and placebo was 16.4 mm ( 95 % confidence interval : 6.3 to 26.6 mm ) . The results on QoL were supported by an increase of T helper lymphocytes ( CD4 + ) and the CD4+/CD8 + ratio ( p<0.05 ) . Overall , PS76A2 was well tolerated . Local reactions at the injection sites occurred dose-dependently , but were mild at the low and medium dose levels OBJECTIVE The paper presents the role of immunomodulatory treatment with Iscador QuS and Intron A of women with CIN1 and CIN2 with concurrent HPV infection . MATERIAL AND METHODS Clinical material consisted of 96 women aged 18 - 52 years of life . The women were divided into three groups . Group A ( 35 women ) treated with Iscador QuS administered s.c . twice a week for 3 months , group B ( 30 women ) treated with Intron A , administered twice a week in the cervical injections for 3 months and control group K ( 31 women ) without treatment followed up with cytology and colposcopy . RESULTS In the group A ( Iscador QuS )  CIN remission was observed in slightly higher percentage ( non significant ) comparing to the control group . In the group B ( Intron A ) remission CIN was observed in 24 ( 80 % ) cases which was statistically significant comparing to the control and A groups . There were no progression of CIN in the group B and the stationery process was observed statistically more frequent comparing to the control and A groups . There was observed statistically higher percentage of cases without HPV infection in all groups during the experiment . The remission concerned both high and low oncogenic potency viruses . In the highest percentage CIN with concurrent HPV infection remission was observed in the B ( Intron A ) group . CONCLUSIONS 1/Iscador QuS and specially Intron A increases the CIN1 and CIN2 remission rate . 2/These two agents may also affect the HPV remission There is still no therapy method in the colorectal cancers that is good enough for such a complex disease . Combined surgery , chemotherapy , and radiotherapy improved survival , but the side effects and the poor performance status of the patients seriously affect the use of these methods . We used a therapeutical approach of surgery and chemotherapy combined with biotherapy by Viscum album extract Isorel , aim ing to improve the patients ' resistance to the disease and to render the treatment 's side effects more tolerable . Isorel is aqueous extract well known for its anticancer effects obtained by various in vitro and in vivo experimental models and which was vali date d by an in vitro bioassay on murine melanoma B16F10 and human cervical carcinoma HeLa cells . Isorel strongly reduced human colon cancer HT 29 cell line growth in vitro in the MTT bioassay . Hence , it was further used in a prospect i ve , r and omized , and controlled study which compared the postoperative results for patients with colorectal cancer stages Dukes C ( 40 patients ) and D ( 24 patients ) who , beside surgery , received either only chemotherapy ( 5-FU ) , 6 cycles ( either the Mayo or the De Gramont protocol ) or chemotherapy combined with Isorel biotherapy . These 64 patients were r and omly allocated into three groups " only chemotherapy " for 21 cases , chemo + biotherapy for 29 cases and 14 patients underwent only surgery as the control group . We noted no toxic deaths due to either chemo or biotherapy . The patients operated on and treated with chemo and biotherapy had median survival significantly better and a cumulative proportion survival ( Kaplan-Maier ) superior to those of the patients receiving only postoperative chemotherapy . Thus , colorectal cancer patients seem to benefit in terms of survival from combined postoperative chemotherapy and Isorel biotherapy , either adjuvant or palliative Mistletoe preparations such as Iscador ® ( Weleda , Schwäbisch Gmünd , Germany ) are commonly used in complementary and alternative / anthroposophic medicine for many cancer indications , particularly for solid cancers . Efficacy of this complementary therapy is still controversial . Objective : Does long-term therapy with Iscador show any effect on survival , tumor progression and psychosomatic self-regulation of patients with breast cancer ? Patients and Methods : Prospect i ve recruitment and long-term follow-up of two controlled cohort studies : ( 1 ) R and omized matched-pair study ( 38 pairs ) : breast cancer patients without any recurrences or metastases and no mistletoe therapy  were matched for prognostic factors . By pairwise r and om allocation , one of the patients was suggested mistletoe therapy to be applied by the attending physician . ( 2 ) Non-r and omized matched-pair study ( 84 pairs ) : breast cancer patients without recurrences or metastases that already received mistletoe therapy  were matched to control patients without Iscador therapy . Results : For overall survival , the nonr and omized study shows significant effects in favor of Iscador therapy : hazard ratio HR estimate and 95 % confidence interval CI : 0.43 ( 0.27 - 0.68 ) . The effect of long-term Iscador therapy on tumor progression as measured by the time to local recurrences , lymphatic or distant metastases in breast cancer patients without any such events at first diagnosis , is in most cases significant in favor of the Iscador group , in the r and omized as well as in the non-r and omized study . Psychosomatic self-regulation in the Iscador  group improves significantly within 12 months compared with the control group in the r and omized as well as in the non-r and omized study : estimate of the median difference and 95 % CI : 0.35 ( 0.05 - 0.60 ) , respectively 0.20 ( 0 - 0.35 ) . Conclusion : Iscador shows a clinical ly relevant effect on breast tumor progression as measured by overall survival as well as by the time to recurrences , lymphatic or distant metastases . In the short term , psychosomatic self-regulation increases more markedly under complementary Iscador therapy than under conventional therapy R and omized , controlled trials ( RCTs ) of herbal interventions often inadequately describe important aspects of their methods ( 1 - 4 ) . Although the quality of reporting of these trials may be improving with time , many still lack important information , particularly about the composition of the herbal intervention ( 4 , 5 ) . Crude herbal drugs are natural products and their chemical composition varies depending on several factors , such as geographic source of the plant material , climate in which it was grown , and time of harvest . Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared among manufacturers ( 6 - 14 ) . Even when herbal products are st and ardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality , there is variation in the concentrations of other constituents . These variations can result in differences in pharmacologic activity in vitro ( 15 ) and in bioavailability in humans ( 16 ) . Mindful of these issues , we elaborated on the 22-item checklist of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement ( 17 ) to help authors and editors improve reporting of RCTs of herbal interventions . Methods We developed these reporting recommendations in 3 phases that included premeeting item generation , a consensus meeting , and postmeeting feedback . The individuals who participated are listed in the Appendix . To generate items , 1 investigator conducted telephone interviews of 16 participants with expertise in the method and reporting of RCTs ( 5 participants ) , pharmacognosy ( 4 participants ) , herbal medicinal products ( 5 participants ) , medical statistics ( 1 participant ) , and herbal product manufacturing ( 1 participant ) . The investigator asked participants to suggest revisions to existing CONSORT checklist items and also to additional items required for reporting trials of herbal interventions . He asked participants to nominate revisions or new items on the basis of empirical evidence that not reporting the item would bias estimates of treatment effect . When no empirical evidence was available , commonsense reasoning was acceptable . After completing all telephone calls , the investigator thematically grouped items and circulated them by e-mail to each participant for review . Fourteen participants attended the consensus meeting . The meeting began with a review of the premeeting checklist item suggestions . We emphasized minimizing item elaborations and additions and basing elaborations on evidence whenever possible . Each item suggestion was presented and followed by debate for its inclusion , deletion , or modification . This process was repeated until all items were review ed and a consensus emerged . After the consensus meeting , we circulated a draft summary report to all participants to ensure that it accurately represented decisions made during the consensus meeting . We then circulated the report to the wider CONSORT Group for input and revised it on the basis of their suggestions . Ethical approval was obtained from The University of Toronto Health Sciences Ethics Review Committee on 23 January 2004 . Financial support for the consensus meeting was provided by the Canadian Institutes of Health Research . The funding body had no role in the design , conduct , or analysis of this study and did not influence the decision to su bmi t the manuscript for publication . All research ers are independent of the funders . Results The group did not recommend any new CONSORT checklist items or modifications in the CONSORT flow diagram . We did , however , elaborate on 9 of the 22 CONSORT checklist items to enhance their relevance to trials of herbal interventions ( Table , Figure ; Appendix Table ) , including minor recommendations for 8 items ( item 1 [ title and abstract ] , item 2 [ background ] , item 3 [ participants ] , item 6 [ outcomes ] , item 15 [ baseline data ] , item 20 [ interpretation ] , item 21 [ generalizability ] , and item 22 [ overall evidence ] ) and detailed recommendations for 1 item ( item 4 [ interventions ] ) . Table . Proposed Elaboration of CONSORT Checklist Item 4 for Reporting R and omized , Controlled Trials of Herbal Medicine Interventions Figure . The high-pressure liquid chromatography chemical fingerprint for the extract of Ginkgo biloba L Appendix Table . Proposed Elaborations of CONSORT Items for R and omized , Controlled Trials of Herbal Medicine Interventions The Table shows the detailed recommendations for item 4 and an example of good reporting related to each recommendation . These recommendations begin with the words where applicable to indicate that all information suggested may not be applicable to every type of herbal medicine intervention . For example , an herbal medicinal product comprising crude herbal material ( for example , leaves and stems ) simply prepared as a tea or decoction does not require description of the type and concentration of solvent used and the ratio of herbal drug to extract ( item 4B.3 ) . Also , not every herbal medicine intervention will have a finished product or extract name or manufacturer ( item 4A.2 ) , but instead may be made by the investigators specifically for the study . In such circumstances , all methods used in preparing and formulating the product must be reported . Similarly , item 4F is not required for herbal interventions when the practitioner is not a part of the intervention . With these exceptions , we recommend that all information shown in the Table be reported for all herbal interventions . Discussion We developed recommendations to be used in conjunction with the existing CONSORT checklist when reporting RCTs of herbal interventions . In particular , we thought it imperative that reports of RCTs provide clear and complete descriptions of the herbal intervention . We think that our recommendations might also be relevant for reporting herbal interventions in other research design s , whether pre clinical ( for example , in vivo or in vitro ) or clinical ( for example , N of 1 trials ) , and refer interested readers to a detailed explanatory document that further describes each of our recommendations and provides additional examples of good reporting ( 22 ) . We hope that authors find our recommendations instructive and that journals will endorse their use and modify their instructions to authors accordingly Non-selected tumor patients ( n=12 ) with various solid carcinomas were treated continuously twice weekly over 48 weeks with the aqueous mistletoe extract PS76A2 , st and ardized to active mistletoe lectin . The preparation was applied subcutaneously at a concentration of 15 ng mistletoe lectin per 0.5 ml . Cellular immune response and safety were determined at various times during and after the therapy . In the course of treatment , virtually all the investigated immunoparameters were raised compared to the baseline values at the start of treatment . The statistically significant rises in the cell count of total lymphocytes , monocytes and natural killer ( NK ) cells was noteworthy . The differences in comparison with the baseline values at the various measuring times during treatment were up to 35 % . In the first weeks of treatment at least , the raised cell count of NK cells correlated with the significantly increased cytotoxic activity versus tumor cells ex vivo . The NK factor ( product of NK cells and ex vivo activity ) was determined to assess the total NK activity more accurately , which rose up to 50 % compared to the baseline value . Other lymphatic sub population s , for instance CD3 + , CD8 + , CD3+CD4 + and CD3+CD8 + cells , also revealed distinct rises in cell count in the course of treatment . Within 6 weeks after completion of treatment , the overall values dropped again ; but for a series of immunoparameters -- in particular for the NK cells -- they were still raised in comparison to the baseline values . The extensive laboratory diagnostics ( haematology , clinical chemistry ) showed that treatment with the st and ardized mistletoe extract PS76A2 was well tolerated by all patients . In single cases , local reactions at the injection sites were of a minor nature and reversible within two days . Summarizing , it can be stated that the st and ardized mistletoe extract PS76A2 significantly improved the  immune status of tumor patients and was administered safely over a long period In making treatment decisions , doctors and patients must take into account relevant r and omised controlled trials ( RCTs ) and systematic review s. Relevance depends on external validity ( or generalisability)--ie , whether the results can be reasonably applied to a definable group of patients in a particular clinical setting in routine practice . There is concern among clinicians that external validity is often poor , particularly for some pharmaceutical industry trials , a perception that has led to underuse of treatments that are effective . Yet research ers , funding agencies , ethics committees , the pharmaceutical industry , medical journals , and governmental regulators alike all neglect external validity , leaving clinicians to make judgments . However , reporting of the determinants of external validity in trial publications and systematic review s is usually inadequate . This review discusses those determinants , presents a checklist for clinicians , and makes recommendations for greater consideration of external validity in the design and reporting of RCTs PURPOSE The indication for topic chemotherapy or immunotherapy for well differentiated , noninvasive superficial bladder cancer remains controversial . Side effects of these treatments promoted use of unconventional therapies with cytokines , immunomodulators and mistletoe extracts . However , there are no controlled clinical data available on the efficacy of these extracts for bladder cancer . We evaluate the influence of subcutaneously applicated mistletoe lectin on bladder tumor recurrence after transurethral resection . MATERIAL S AND METHODS The study consists of 45 patients with pTa G1 - 2 bladder cancer treated with transurethral resection during a 3-year period . Median patient age was 65 years and 33 patients were male . The study cohort was r and omly divided into a treatment group receiving adjuvant therapy with mistletoe lectin and a control group receiving no additional treatment . Patients in the treatment group received mistletoe lectin according to schedule 2 weeks after transurethral resection . Clinical followup was assessed 3 , 6 , 9 , 12 and 18 months after the initial resection , and included uretherocystoscopy . RESULTS Both study arms comprised similar patients with regard to total number of previous tumors ( mean 2.6 versus 2.9 ) , number of primary lesions ( 14 versus 12 ) and number of recurrent tumors ( 8 versus 11 ) . After followup of 18 months the recurrence-free interval in both study arms was similar ( p = 0.76 ) and the total number of recurrences comparable ( p = 0.48 ) . CONCLUSIONS Subcutaneous use of mistletoe lectin as adjuvant treatment after transurethral resection does not seem to affect the time to first recurrence , total number of recurrences or recurrence-free outcome 35 patients suffering from malignant stage III/IV glioma were enrolled into a prospect ively r and omized clinical trial . All patients were provided with st and ard oncologic treatment ( neurosurgery , radiation , basic clinical care according to protocol and indication ) and r and omly divided into a ) treatment group : receiving subcutaneous injections of a ML ( a galactoside-specific lectin from mistletoe ) st and ardized mistletoe extract , 1 ng ML-1/kg BW , twice a week for 3 months , starting on day 1 post surgery , b ) control group : without additional complementary treatment .  Immunophenotyping of peripheral blood leukocytes was done by flow cytometry ( pre surgery ; day 1 , week 1 , month 3 and 6 post surgery ) to evaluate the immunomodulating capacity of ML-1 st and ardized mistletoe extract . St and ard tumor destructive treatment of glioma proved to be suppressive for peripheral blood lymphocytes , since all subsets tested revealed statistically significant down regulation . Unlike the lymphocyte counts and activities of patients from the control group who gave preoperative values after 3 - 6 months ) , mistletoe treatment induced a statistically significant up regulation of cell counts ( CD-3 , CD4 , CD-8 cells ) and activities ( CD-25 , HLA/DR positive cells ) after 3 months , as compared to preoperative values . Obviously , a strong immunoprotective/immunostimulatory effect was induced by the treatment of glioma patients with ML-1 st and ardized mistletoe extract which correlated with an improved quality of life , as determined by a st and ard question naire ( Spitzer ) This review assesses the evidence of the efficacy of mistletoe extracts in cancer patients from controlled clinical trials in humans . We used a list of predefined criteria for good methodology to select the trials which had the highest quality and interpreted the results with emphasis on the quality . An extensive search of the literature yielded 11 controlled trials in which at least an attempt was made for unbiased allocation into the contrasted treatment groups . The average quality of the trials appeared to be disappointingly poor . It concerned trials for bronchus carcinoma , colorectal carcinoma , mamma carcinoma , gastric cancer and female genital cancer . In the trials the results were in favour of mistletoe treatment ; the principle endpoint was mostly survival time . Only one trial could not show a beneficial effect , but this was the trial with the highest method ological score . Well performed r and omized , double-blind clinical trials on carefully chosen patient population s are needed in order to make assessment s of any efficacy . Further evidence should also consist of a more solid demonstration of the mechanisms of action from laboratory studies . St and ardization methods on active substances should be improved as there are apparent component variations between , but also within the preparations which were used in clinical trials . Considering the state of affairs we can not recommend the use of mistletoe extracts in the treatment of cancer patients with an exception for patients involved in clinical trials OBJECTIVES Herbal medicine ( phytotherapy ) is widely used , but the evidence for its effectiveness is a matter of ongoing debate . We compared the quality and results of trials of  Western phytotherapy and conventional medicine .  STUDY DESIGN AND SETTING A r and om sample of placebo-controlled trials of  Western phytotherapy  was identified in a comprehensive literature search ( 19 electronic data bases ) . Conventional medicine trials matched for condition and type of outcome were selected from the Cochrane Central Controlled Trials Register ( issue 1 , 2003 ) . Data were extracted in duplicate . Trials described as double-blind , with adequate generation of allocation sequence and adequate concealment of allocation were assumed to be of higher method ological quality . RESULTS Eighty-nine herbal medicine and 89 matched conventional medicine trials were analyzed . Studies of Western herbalism were smaller , less likely to be published in English , and less likely to be indexed in MEDLINE than their counterparts from conventional medicine . Nineteen ( 21 % ) herbal and four ( 5 % ) conventional medicine trials were of higher quality . In both groups , smaller trials showed more beneficial treatment effects than larger trials . CONCLUSIONS Our findings challenge the widely held belief that the quality of the evidence on the effectiveness of herbal medicine is generally inferior to the evidence available for conventional medicine Aviscumine is a ribosome-inactivating protein with potent antitumour activity in vitro and in vivo and is an Escherichia coli-derived recombinant counterpart of natural mistletoe lectin-I. The current study was performed to determine the safety profile , dose-limiting toxicity ( DLT ) and maximum tolerated dose ( MTD ) of a prolonged infusion of aviscumine in cancer patients .  Aviscumine was given once weekly as a 24 h central intravenous infusion in patients with advanced , refractory progressive solid malignant tumours . Fourteen fully eligible patients ( 11 male , 3 female ) with a median age 58 yrs ( range 41 - 77 ) were enrolled . They had histologically verified disease , were 18 yrs old , had an ECOG PS 2 and adequate bone marrow , liver and renal function .  DLT was defined as any non-haematological grade 3 - 4 toxicity ( Common Toxicity Criteria [ CTC ] version 2.0 ) , neutrophil count < 500/ microl for 7 days , febrile neutropenia or thrombocytopenia grade 4 . The MTD was defined as the dose level below the dose at which 2 patients per dose level experienced a DLT during the first treatment cycle . Colorectal cancer , soft tissue sarcoma and pancreatic cancer were the most common tumour types . Dose levels of aviscumine ranged from 4 to 6 microg/kg . The median number of cycles was 2.8 ( range , 2 - 8 ) . Common side effects in cycle 1 were fatigue , fever , nocturia , urticaria , erythema and pruritus . DLTs occurred in 2/3 patients on the 6 microg/kg dose level and consisted of increases in ASAT grade 3 , ALAT grade 3 , gammaGT grade 3/4 , hypokalemia grade 3 and fatigue grade 3 . No DLTs were observed on dose levels 4 and 5 microg/kg . The best response ( RECIST ) was stable disease in 4 pts , lasting for 4 - 8 cycles . Pharmacokinetics indicated that potentially active plasma levels of the compound were maintained during the entire infusion . We conclude that the recommended dose for weekly 24 h infusions of Aviscumine should be 5 microg/kg To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results
BACKGROUND Mistletoe extracts are commonly used in cancer patients .
It is cl aim ed that they improve survival and quality of life ( QOL ) in cancer patients .
OBJECTIVES To determine the effectiveness , tolerability and safety of mistletoe extracts given either as monotherapy or adjunct therapy for patients with cancer .