ABSTRACT
Background: Mistletoe is an herb that grows on duku plants (Lancium demosticum) and is known as benalu duku (BD) in Indonesia. It is predicted to have benefits such as anticancer or antiviral properties, and it is also thought to have anti-diabetic pharmacological activity. Quercetin-like compounds (QLCs) are secondary metabolites with antidiabetic activity that are expected to lower blood sugar levels in animals after oral administration.Objective: This study aimed to analyze the ability of QLCs to reduce random blood sugar levels using experimental animals as clinical models.Material and methods: The research method used was exploratory, which used a before-after test model, and observations were made on the random blood sugar levels after treatment. Secondary metabolites were extracted from BD leaves, which were then screened. Diabetes was induced in 30 rats (Rattus norvegicus) by the administration of streptozotocin at 0.045 mg/g body weight daily for 2 days. The antidiabetic effects of the secondary metabolite at doses of 0.5 mg/kg body weight (twice a day) when administered orally for up to 5 days were tested in diabetic rats. The random sugar levels (mg/dL) were measured using a One Touch Ultra Plus medical device for observation of randomized blood sugar levels. Results and novelty: The results revealed that the secondary metabolite, as an analyte from the BD leaf extract, can significantly reduce random blood sugar levels.Conclusion: The secondary metabolite extracted from BD, could be used to treat diabetes in rats.
Subject(s)
Blood Glucose , Diabetes Mellitus, Experimental , Hypoglycemic Agents , Plant Extracts , Quercetin , Animals , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/blood , Rats , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/administration & dosage , Quercetin/pharmacology , Quercetin/analogs & derivatives , Quercetin/therapeutic use , Blood Glucose/analysis , Blood Glucose/drug effects , Male , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Mistletoe/chemistry , Administration, Oral , Plant Leaves/chemistryABSTRACT
BACKGROUND: Patients with advanced pancreatic cancer have limited survival and few treatment options. We studied whether mistletoe extract (ME), in addition to comprehensive oncological treatment and palliative care, prolongs overall survival (OS) and improves health-related quality of life (HRQoL). METHODS: The double-blind, placebo-controlled MISTRAL trial was conducted in Swedish oncology centers. The main inclusion criteria were advanced exocrine pancreatic cancer and Eastern Cooperative Oncology Group (ECOG) performance status 0-2. The subjects were randomly assigned to ME (n=143) or placebo (n=147) and were stratified by study site and by eligibility (yes/no) for palliative chemotherapy (June 2016-December 2021). ME or placebo was injected subcutaneously three times a week for nine months. The primary endpoint was overall survival (OS); one of the secondary endpoints was the HRQoL dimension global health/QoL (EORTC-QLQ-C30), as assessed at seven time points over nine months. Trial registration: EudraCT 2014-004552-64, NCT02948309. RESULTS: No statistically significant benefit of adding ME to standard treatment was seen with respect to either OS or global health/ QoL. The adjusted hazard ratio for OS was 1.13 [0.89; 1.44], with a median survival time of 7.8 and 8.3 months for ME and placebo, respectively. The figures for the HRQoL dimension "global health/QoL" were similar in the two groups (p=0.86). The number, severity, and outcome of the reported adverse events were similar as well, except for more common local skin reactions at ME injection sites (66% vs. 1%). CONCLUSION: ME is unlikely to have a clinically significant effect on OS or the HRQoL dimension global health/QoL when administered in patients with advanced pancreatic cancer in addition to comprehensive cancer care.
Subject(s)
Mistletoe , Pancreatic Neoplasms , Plant Extracts , Quality of Life , Humans , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/mortality , Plant Extracts/therapeutic use , Male , Female , Middle Aged , Double-Blind Method , Aged , Treatment Outcome , Palliative Care/methods , Adult , SwedenABSTRACT
PURPOSE: Mistletoe treatment in cancer patients is controversial, and a Cochrane review concluded that due to heterogeneity, performing a meta-analysis was not suitable. However, several systematic reviews included meta-analyses in favor of mistletoe. The aim of this work was to assess the influence of the methodological quality of controlled studies on the results of a meta-analysis regarding overall survival. METHODS: Between April and August 2022, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and Web of Science were systematically searched. In addition, reference lists of previously published meta-analyses were checked for relevant publications. A random effects meta-analysis with clustering was performed. The risk of bias within the studies was assessed using ROB 2.0 and ROBINS-I. RESULTS: The search identified 4685 hits, and 28 publications reporting on 28 298 patients were included in the quantitative analysis. Overall, the analysis led to a significant result in favor of mistletoe therapy (overall HR = 0.61 with 95% CI [0.53;0.7]). According to our subgroup analysis of randomized studies, studies of higher quality (lower risk of bias) did not lead to a significant result in favor of mistletoe therapy (HR = 0.78; CI = [0.30; 2.00]). CONCLUSIONS: In the case of mistletoe therapy, the results of the meta-analysis strongly depended on the methodological quality of the included studies. Calculating meta-analyses that include low-quality studies may lead to severe misinterpretation of the data.
Subject(s)
Mistletoe , Neoplasms , Humans , Meta-Analysis as Topic , Neoplasms/mortality , Neoplasms/drug therapy , Neoplasms/therapy , Phytotherapy/methods , Randomized Controlled Trials as TopicABSTRACT
Associational effects are a phenomenon in which herbivore damage on co-occurring plant species is influenced by neighboring plants. Mistletoes are a group of shrubs that obtain nutrients from host plants through haustoria. Despite the potential for mistletoe herbivory to be affected by associational effects with their hosts, the effects of host and mistletoe functional traits on mistletoe herbivory have been largely overlooked. This study aimed to evaluate the associational effects of host plants and the direct effects of mistletoe functional traits on mistletoe herbivory. To achieve this, we measured leaf herbivory and leaf traits of three mistletoe species (Dendrophthoe pentandra, Scurrula chingii var. yunnanensis, and Helixanthera parasitica) and their associated 11 host species during both dry and wet seasons. Our results showed that leaf herbivory of D. pentandra and S. chingii var. yunnanensis differed significantly on their respective host species, but H. parasitica did not. The relationships between mistletoe and the paired host herbivory differed between seasons, with a stronger positive relationship observed during the dry season. Furthermore, significant relationships were observed between paired leaf carbon, leaf nitrogen, and condensed tannin in mistletoes and their host plants, indicating that host plants can affect mistletoes' leaf functional traits. A group of mistletoe leaf traits provided significant predictions for leaf herbivory: leaves with higher leaf thickness and leaf total nitrogen showed higher herbivory. Overall, our study reveals that mistletoe leaf herbivory is directly affected by its leaf traits and indirectly affected by host associational effects, primarily through changes in mistletoes' leaf traits.
Subject(s)
Herbivory , Mistletoe , Plants , Carbon , Nitrogen , Plant LeavesABSTRACT
MOTIVATION: Cancer patients often use complementary and/or alternative medicine, such as mistletoe therapy, alongside conventional cancer therapies. In Switzerland, so far not much is known about treatment patterns of breast cancer patients using integrative oncology. Solid knowledge on complementary care utilization may help to enhance integrative oncology care in Switzerland. METHODS: In this exploratory, descriptive database study, we investigated the treatment pathways of a cohort of breast cancer patients who received mistletoe therapy and were documented in the cancer registry of an anthroposophic Swiss hospital offering integrative oncology treatments. RESULTS: Patients treated with mistletoe in this cohort are in median 10 years younger than Swiss breast cancer patients as a whole. Only 5.8% of these patients were treated with mistletoe alone, while 60.5% of them supplemented chemotherapy and/or hormone therapy and/or surgery and/or radiation with mistletoe therapy. Nearly 80% of patients started conventional therapy followed by additional mistletoe therapy or started mono mistletoe therapy after completion of conventional therapies. The median time from initial diagnosis to hospital admission (inpatient and/or outpatient) was less than one year. Almost ¾ of the patients were treated in an outpatient setting only. CONCLUSION: From our data, it appears that younger breast cancer patients are more likely to use mistletoe therapy simultaneously with or following their conventional medical therapies. The extent to which these patients discuss their mistletoe therapy and eventually other complementary and/or alternative therapies with their primary oncologists is not clear from the data. We therefore recommend that (Swiss) oncologists should openly discuss the desire for integrative oncology therapies, especially with their younger breast cancer patients, in order to find the best holistic care pattern for these patients.
Subject(s)
Breast Neoplasms , Integrative Oncology , Mistletoe , Viscum album , Humans , Female , Breast Neoplasms/drug therapy , Plant Extracts/therapeutic use , RegistriesABSTRACT
BACKGROUND: Breast cancer is the most common cancer type in women and quality of life an essential part of patients' well-being. Although the treatment with mistletoe extracts is covered by multiple cancer guidelines and reviews, it is uncertain whether mistletoe extracts can improve the quality of life in breast cancer patients. We therefore performed a systematic review and meta-analysis on this topic. METHODS: This systematic review included randomized clinical trials (RCTs) and non-randomized studies of intervention (NRSIs) comparing the quality of life in breast cancer patients treated with mistletoe extracts as add-on therapy to control groups treated conventionally. We searched previous systematic reviews and multiple databases until January 2023. We conducted a meta-analysis and assessed the risk of bias according to the Cochrane Handbook via RoB 2 and ROBINS-I and the certainty of evidence via GRADE, respectively. RESULTS: Nine RCTs and 7 NRSIs with 833 and 2831 participants, respectively, were included. The pre-post changes for the quality of life resulted in a pooled standardized mean difference for RCTs of SMD = 0.61 (95% CI 0.47-0.75; P < .0001) and for retrospective NRSIs of SMD = 0.46 (95% CI 0.10-0.82; P = .01). The risk of bias was low to high for the RCTs and serious for all NRSIs. The certainty of evidence was moderate for RCTs and very low for NRSIs. DISCUSSION: Our results indicate a clinically relevant, medium-sized effect of mistletoe extracts on the quality of life in breast cancer patients which may be based on the immunomodulating effects of mistletoe extracts during chemotherapy. The limitations of evidence include the risk of bias which is mainly caused by the difficulty of blinding. Further RCTs and real-world evidence need to confirm this result, especially in the setting of neoadjuvant chemotherapy and in breast cancer survivors.
Subject(s)
Breast Neoplasms , Mistletoe , Female , Humans , Breast Neoplasms/drug therapy , Quality of LifeABSTRACT
The genus Psittacanthus (Loranthaceae) is widely distributed in the Neotropical region, where it is known for its large, colourful, scentless flowers. Until very recently, all Psittacanthus species were regarded as exclusively hummingbird-pollinated and the large species radiation in the genus attributed to the interactions with bird dispersers and pollinators. P. eucalyptifolius (Kunth) G.Don. is the only species reported as bee-pollinated. Here we describe the floral biology, floral visitors, and the reproductive system of P. eucalyptifolius in an Amazonian savanna, Brazil. We also compare the pollination success (reproductive performance) among different Psittacanthus species reported in previous studies. Psittacanthus eucalyptifolius produces sweet-scented flowers, and a small quantity of concentrated nectar. At least five species of scopate bees were recorded visiting and carrying pollen of P. eucalyptifolius. Xylocopa frontalis carried most pollen, visited more flowers, remained longer, and touched reproductive parts of flowers in >95% of the observed visits. Experiments indicate that P. eucalyptifolius is partially autocompatible (39% autonomous pollination) but depends on pollinators to achieve higher performance (~78% in control), indicating that bees can be as effective as birds in pollinating this group of mistletoes.
Subject(s)
Loranthaceae , Mistletoe , Viscum album , Animals , Bees , Birds , Flowers , Plant Nectar , PollinationABSTRACT
INTRODUCTION: The introspective experience of cancer patients using mistletoe therapy has received little scientific interest, although it is crucial for a holistic understanding of this therapy. This study contributes to patient-centered research and treatment by documenting the subjective experiences of individuals undergoing mistletoe therapy. METHODS: In this qualitative, explorative study, 20 outpatients with a history of various cancer types were recruited from Arlesheim Hospital (Arlesheim, Switzerland). All patients received subcutaneous mistletoe therapy for at least 2 years (median 7.5 years). Data was collected through 2 semi-structured, in-depth interviews per patient. Qualitative content analysis was applied to examine the data. The individual experience of mistletoe therapy was analyzed in relation to 6 predefined levels of human experience: physical, vital, emotional, mental, spiritual and social. In addition, 3 further aspects, considered as cross-dimensional perspectives, emerged out of the material: warmth, immune strengthening, and general wellbeing. RESULTS: Data analysis revealed considerable heterogeneity among patients' experiences with mistletoe therapy. The importance of specific aspects became apparent, such as increased vitality to manage daily life, greater emotional and mental stability, warmth as a multidimensional phenomenon, feelings of safety and protection through mistletoe therapy, heightened self-awareness and improved self-care, as well as sensations of spiritual connectedness. CONCLUSIONS: Prior to this study it had not been shown that cancer patients using mistletoe therapy do have observations on different levels of experience. These results may lead to a deeper understanding of patients receiving mistletoe therapy, enabling them to be supported in a more holistic way both during mistletoe treatment and on their life path. Further investigations into the effects of mistletoe therapy on the emotional, mental, and spiritual level are warranted.
Subject(s)
Mistletoe , Neoplasms , Viscum album , Humans , Neoplasms/therapy , Phytotherapy , Patient Outcome AssessmentABSTRACT
Plant spatial distribution is an important topic in ecology as it determines species coexistence and biodiversity dynamics. Usually, plants show clustered distributions in nature. Mistletoes are a good example of aggregated distributions, as they form dense aggregations due to several factors (availability of competent hosts, seed dispersal vectors, microclimate conditions). We analysed four native mistletoe species with divergent life histories and host ranges: Desmaria mutabilis and Tristerix corymbosus from the temperate rainforests of southern Chile; and Tristerix aphyllus and Tristerix verticillatus from the northern semi-desert zone. While T. corymbosus and T. verticillatus have a wide host range, T. aphyllus and D. mutabilis are specialists that can parasitize only a few plant species. We hypothesized that specialized species would be more aggregated due to ecological and environmental restrictions. We used heterogeneous Poisson models to quantify spatial aggregation. Three of the four mistletoe species were spatially clustered at both environments, with aggregation being stronger in the temperate rainforest of southern Chile and particularly in the host-specialist species. Our results suggest that environmental constraints are more important than ecological constraints (host range) in shaping mistletoe spatial structure. Mistletoe aggregated spatial distribution depends primarily on the environment that they inhabit, which conditions host spatial availability, and arrangement.
Subject(s)
Mistletoe , Viscum album , Biodiversity , Rainforest , ChileABSTRACT
Viscum album L. (mistletoe) is a semiparasitic plant of the Santalaceae family. A valuable group of bioactive compounds in mistletoe are triterpene acids (TTAs), which possess anti-inflammatory and anticancer properties. Parrotia persica and Carpinus betulus are the most common hosts of mistletoe in the Hyrcanian forests of Iran. This study was performed to compare the content of oleanolic acid (OA), betulinic acid (BA), and ursolic acid (UA) in the mistletoe foliage (stems and leaves) from P. persica and C. betulus in various seasons for the first time. The results showed that OA was the prevailing TTA in all samples, while UA was found in none of them. The maximum amount of OA (12.38 mg/g dry weight [DW]) and BA (1.68 mg/g DW) was detected in V. album from P. persica in summer. The minimum amount of OA (5.58 mg/g DW) and BA (0.72 mg/g DW) was observed in that growing on C. betulus in winter. However, the mistletoe from C. betulus showed the greatest level of OA in spring (9.06 mg/g DW) and BA in summer and autumn (0.92 and 0.97 mg/g DW, respectively). The data collected in this study complement existing research on this subject from around the world.
Subject(s)
Mistletoe , Triterpenes , Viscum album , Trees/parasitology , Seasons , Plant Extracts , Forests , Ursolic AcidABSTRACT
PURPOSE: To mitigate side effects of conventional cancer care and improve quality of life, many patients with breast cancer in German-speaking countries opt for mistletoe therapy in addition to standard treatment. To understand the value for users, we evaluated the domain "Patient and Social aspects" in a health technology assessment on complementary mistletoe therapy in patients with breast cancer. METHODS: A systematic review was conducted according to PRISMA guidelines. Fifteen electronic databases and the internet were searched. Qualitative studies were analyzed using qualitative content analysis; quantitative studies were systematically summarized in evidence tables. RESULTS: Seventeen studies out of 1203 screened publications with 4765 patients and 869 healthcare professionals were included in the review. The median proportion of patients using mistletoe therapy was 26.7% (range: 7.3-46.3%). Predictors for use were younger age and higher educational level. Main reasons for patients' use of mistletoe therapy were to leave nothing untried and to be actively involved in the treatment process. Reasons against use were related to a lack of knowledge or uncertainty regarding effectiveness and safety. Physicians mainly aimed to support the patient's physical condition as main reason for use and a lack of resources and knowledge as main reason against use. CONCLUSION: Mistletoe therapy was commonly used in the treatment of breast cancer despite a lack of scientific knowledge among patients and physicians. Transparent communication on motivation for use and its potential effect enables realistic expectations. Relatively small samples of mistletoe therapy users limit the representativeness and validity of our results.
Subject(s)
Antineoplastic Agents, Phytogenic , Breast Neoplasms , Mistletoe , Viscum album , Humans , Female , Plant Extracts/therapeutic use , Phytotherapy/adverse effects , Phytotherapy/methods , Quality of Life , Technology Assessment, Biomedical , Antineoplastic Agents, Phytogenic/adverse effects , Breast Neoplasms/drug therapyABSTRACT
No Abstract Available.
Subject(s)
Biological Products , Mistletoe , Urinary Bladder Neoplasms , Humans , Administration, Intravesical , Urinary Bladder Neoplasms/drug therapy , Plant Extracts/therapeutic useABSTRACT
Targeted delivery of a toxin substance to cancer cells is one of the most recent cancer treatment options. Mistletoe Lectin-1 (ML1) in Viscum album L. is a Ribosome-inactivating proteins with anticancer properties. Therefore, it appears that a recombinant protein with selective permeability can be generated by fusing ML1 protein with Shiga toxin B, which can bind to Gb3 receptor that is abundantly expressed on cancer cells. In this study, we sought to produce and purify a fusion protein containing ML1 fused to STxB and evaluate its cytotoxic activities. The ML1-STxB fusion protein coding sequence was cloned into the pET28a plasmid, then was transformed into E. coli BL21-DE3 cells. Following induction of protein expression, Ni-NTA affinity chromatography was used to purify the protein. Using SDS-PAGE and western blotting, the expression and purification processes were validated. On the SkBr3 cell line, the cytotoxic effects of the recombinant proteins were evaluated. On SDS-PAGE and western blotting membrane, analysis of purified proteins revealed a band of approximately 41 kDa for rML1-STxB. Ultimately, statistical analysis demonstrated that rML1-STxB exerted significant cytotoxic effects on SkBr3 cells at 18.09 and 22.52 ng/L. The production, purification, and encapsulation of rML1-STxB fusion protein with potential cancer cell-specific toxicity were successful. However, additional research must be conducted on the cytotoxic effects of this fusion protein on other malignant cell lines and in vivo cancer models.
Subject(s)
Antineoplastic Agents , Biological Products , Mistletoe , Viscum album , Lectins , Escherichia coli/genetics , Escherichia coli/metabolism , Mistletoe/metabolism , Viscum album/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/pharmacology , Recombinant Proteins/metabolism , Antineoplastic Agents/pharmacology , Biological Products/metabolism , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/pharmacologyABSTRACT
Pancreatic ductal adenocarcinoma is an aggressive malignancy usually detectable at the advanced stage, with a 5-year survival rate of less than 8%. It has been reported that a gene called tumor-protein 63 (TP63) is expressed in an aggressive form of pancreatic cancer with a squamous signature. Thus, inhibiting the activity of p63 can be a means of treating and managing PDA. Different studies have shown that plant constituents are rich and can be a promising source for discovering drug candidates. The extract from mistletoe (Viscum album) is known to contain anticancer compounds; however, the specific molecular mechanism of the bioactive compounds is unknown. This study examines the pancreatic cancer therapeutic potential of the bioactive compounds in the flavonoid and phenolic acid constituents of mistletoe by adopting structural bioinformatics and advanced theoretical chemistry techniques via molecular docking, molecular dynamics simulation, molecular mechanics/generalized Born surface area (MM/GBSA) calculations, pharmacokinetic analysis, and density functional theory analysis. The six best compounds from the flavonoid constituent with the highest binding affinity ranging from -6.8 kcal/mol to -6.7 kcal/mol were selected with the control gemcitabine (-5.5 kcal/mol) for further computational analysis after molecular docking. Furthermore, MM/GBSA calculation showed the highest binding energy for the selected docked compounds, which validates their inhibitory potential. Hence, the molecular dynamics simulation, post-simulation analysis, pharmacokinetics model, and DFT results showed that mistletoe compounds are reliable due to their stable interaction with the target protein and drug-likeness properties.Communicated by Ramaswamy H. Sarma.
Subject(s)
Biological Products , Mistletoe , Pancreatic Neoplasms , Viscum album , Molecular Docking Simulation , Pancreatic Neoplasms/drug therapy , Flavonoids/pharmacology , Molecular Dynamics SimulationABSTRACT
Viscum album L. (Santalaceae) is an important medicinal plant traditionally used to treat several diseases, including cancer therapy. This paper provides detailed morpho-anatomical characteristics of the leaves, stems and berries of Viscum album subsp. album growing as hemi-parasite on the branches of Malus domestica (Suckow) Borkh. (Rosaceae) to aid species identification and botanical characterization. Additionally, for the first time, microchemical analyses of all tissues and Energy Dispersive X-Ray Spectroscopy analyses of the calcium oxalate crystals are provided for the first time. The plant features leathery presents green leaves with parallel veins, small yellow unisexual flowers in 3-flowered cymes, and the dioecious inflorescences usually consist of three flowers, with female flowers generating white fleshy berries, in which a seed is embedded in the mucilaginous mesocarp, normally containing two embryos. Anatomically, the analyzed leaves were isobilateral and amphistomatic, and showed straight anticlinal epidermal cell walls, thick cuticles with epicuticular wax crystalloids, and paracytic stomata. The midrib is flat on both sides and has a single vascular bundle, whereas the strongly shortened petiole is concave-convex in shape and contains five bundles. The stems show a primary structure with a ring of nine vascular bundles enclosing the pith. Calcium oxalate druses and cubic and quadrangular prisms were observed in different plant parts. The results of this study provide new microscopy information that can help in the authentication of mistletoe raw materials.
Subject(s)
Mistletoe , Plants, Medicinal , Viscum album , Viscum album/chemistry , Calcium Oxalate , Plant ExtractsABSTRACT
Context: Bladder cancer is the fourth-most-common cancer in males in the U.S., who develop about 90% of the high-grade, carcinoma in situ (CIS) of non-muscle involved disease (NMIBC). Smoking and occupational carcinogens are well-known causes. For females without known risk factors, bladder cancer can be regarded as a sentinel environmental cancer. It's also one of the costliest to treat due to its high rate of recurrence. No treatment innovations have occurred in nearly two decades; intravesical instillation of Bacillus Calmette-Guerin (BCG), an agent in short supply globally, or Mitomycin-C (MIT-C) is effective in about 60% of cases. Cases refractory to BCG and MIT-C often undergo cystectomy, a procedure with numerous impacts on life styles and potential complications. The recent completion of a small Phase I trial of mistletoe in cancer patients that have exhausted known treatments at Johns Hopkins provides corroboration of its safety, with 25 % showing no disease progression. Objective: The study examined the benefits of pharmacologic ascorbate (PA) and mistletoe for a nonsmoking female patient with an environmental history of NMIBC refractory to BCG, in a non-smoking female with exposures in childhood and early adult life to several known carcinogens, including ultrafine particulate air pollution, benzene, toluene, and other organic solvents, aromatic amines and engine exhausts, and possibly arsenic in water. Design: The research team performed an integrative oncology case study on pharmacologic ascorbate (PA) and mistletoe, both agents shown to activate NK cells, enhance growth and maturation of T-cells, and induce dose-dependent pro-apoptotic cell death, suggesting shared and potentially synergistic mechanisms. Setting: The study began at the University of Ottawa Medical Center in Canada with treatment continuing over six years at St. Johns Hospital Center in Jackson, Wyoming, and George Washington University Medical Center for Integrative Medicine, with surgical, cytological, and pathological evaluations at University of California San Francisco Medical Center. Participant: The patient in the case study was a 76-year-old, well-nourished, athletic, nonsmoking female with high-grade CIS of the bladder. Her cancer was considered to be a sentinel environmental cancer. Intervention: Intravenous pharmacologic ascorbate (PA) and subcutaneous mistletoe (three times weekly) and intravenous and intravesical mistletoe (once weekly) were employed for an 8-week induction treatment, using a dose-escalation protocol as detailed below. Maintenance therapy was carried out with the same protocol for three weeks every three months for two years. Results: The patient has experienced a cancer-free outcome following 78 months of treatments that incorporated intravesical, intravenous, and subcutaneous mistletoe; intravenous PA; a program of selected nutraceuticals; exercise; and other supplementary treatments. Conclusions: This study is the first reported instance of combined treatments to achieve complete remission for high-grade NMIBC refractory to BCG and MIT-C, using intravesical, subcutaneous, and intravenous mistletoe and intravenous PA. It includes pharmacological information on possible mechanisms. In light of the global shortage of BCG, the high proportion of cases refractory to BCG and MIT-C, the unproven use of costly off-label pharmaceuticals, such as gemcitabine, and the relative cost-effectiveness of mistletoe and PA, clinicians should give serious consideration to employing these combined functional medicine treatments for BCG- and MIT-C-refractory NMIBC. Further research is needed with additional patients that can advance our understanding, including standardization of methods for systematically evaluating combined therapies-blinded and non-blinded, nomenclature regarding mistletoe preparation, doses, concentrations, regimes of administration, lengths of treatment, targeted cancer types, and other aspects.
Subject(s)
Antineoplastic Agents , Carcinoma in Situ , Mistletoe , Urinary Bladder Neoplasms , Humans , Male , Adult , Female , Aged , BCG Vaccine/therapeutic use , Urinary Bladder/pathology , Antineoplastic Agents/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Mitomycin/adverse effects , Carcinoma in Situ/drug therapy , Carcinoma in Situ/pathology , Carcinogens , Neoplasm Recurrence, Local/chemically induced , Neoplasm Recurrence, Local/drug therapyABSTRACT
Purpose: Mistletoe extract (ME) is widely used for patients with cancer to support therapy and to improve quality of life (QoL). However, its use is controversial due to suboptimal trials and a lack of data supporting its intravenous administration. Materials and Methods: This phase I trial of intravenous mistletoe (Helixor M) aimed to determine the recommended phase II dosing and to evaluate safety. Patients with solid tumor progressing on at least one line of chemotherapy received escalating doses of Helixor M three times a week. Assessments were also made of tumor marker kinetics and QoL. Results: Twenty-one patients were recruited. The median follow-up duration was 15.3 weeks. The MTD was 600 mg. Treatment-related adverse events (AE) occurred in 13 patients (61.9%), with the most common being fatigue (28.6%), nausea (9.5%), and chills (9.5%). Grade 3+ treatment-related AEs were noted in 3 patients (14.8%). Stable disease was observed in 5 patients who had one to six prior therapies. Reductions in baseline target lesions were observed in 3 patients who had two to six prior therapies. Objective responses were not observed. The disease control rate (percentage of complete/partial response and stable disease) was 23.8%. The median stable disease was 15 weeks. Serum cancer antigen-125 or carcinoembryonic antigen showed a slower rate of increase at higher dose levels. The median QoL by Functional Assessment of Cancer Therapy-General increased from 79.7 at week 1 to 93 at week 4. Conclusions: Intravenous mistletoe demonstrated manageable toxicities with disease control and improved QoL in a heavily pretreated solid tumor population. Future phase II trials are warranted. Significance: Although ME is widely used for cancers, its efficacy and safety are uncertain. This first phase I trial of intravenous mistletoe (Helixor M) aimed to determine phase II dosing and to evaluate safety. We recruited 21 patients with relapsed/refractory metastatic solid tumor. Intravenous mistletoe (600 mg, 3/week) demonstrated manageable toxicities (fatigue, nausea, and chills) with disease control and improved QoL. Future research can examine ME's effect on survival and chemotherapy tolerability.