Large-scale Survey of the Impact of Complementary Medicine on Side-effects of Adjuvant Hormone Therapy in Patients with Breast Cancer.

BACKGROUND/AIM: The present clinical investigation was performed to confirm the benefit of complementary medicine in patients with breast cancer undergoing adjuvant hormone therapy (HT). PATIENTS AND METHODS: The patients (n=1561) were treated according to international guidelines. All patients suffered from arthralgia and mucosal dryness induced by the adjuvant HT. In order to reduce the side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes (bromelaine and papain) and Lens culinaris lectin. On case report formulas, self assessment arthralgia and mucosal dryness were documented before and four weeks after complementary treatment. Validation was carried-out by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely poor tolerability). A total of 1,165 patients suffering from severe side-effects (symptom scores >3) were enrolled in this investigation. RESULTS: Overall, 62.6% of patients (729 out of 1,165) suffering from severe arthralgia and 71.7% of patients (520 out of 725) with severe mucosal dryness significantly benefited from complementary medicine. Mean scores of symptoms declined from 4.83 before treatment to 3.23 after four weeks of treatment for arthralgia and from 4.72 before treatment to 2.99 after four weeks of treatment for mucosal dryness, the primary aims of the present investigation. The reduction of side-effects of HT was statistically significant (p<0.001) after four weeks. CONCLUSION: This investigation confirms studies suggesting a benefit of complementary treatment with the combination of sodium selenite, proteolytic enzymes and L. culinaris lectin in patients with breast cancer.

Complementary medicine down-regulates side-effects of hormone therapy in prostate cancer patients.

AIM: The present clinical investigation was performed to evaluate the benefits of complementary medicine in prostate cancer patients undergoing hormone therapy (HT). PATIENTS AND METHODS: Patients (N=93) were treated according to international guidelines. All patients suffered from side-effects induced by the HT. To reduce the side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes and Lens culinaris (Lc) lectin. On case report formulas (CRFs), self assessment of defined side-effects of HT (arthralgia, mucosal dryness, bone pain and hot flushes) were documented before (T-0) and on days 25 (T-1) and 50 (T-2) after complementary treatment. Validation was carried-out by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely bad tolerability), however, only patients suffering from severe side-effects (symptom scores >3) were enrolled in this investigation. RESULTS: The severity of side-effects of HT was reduced by complementary treatment with sodium selenite, proteolytic plant enzymes and Lc-lectin. The mean scores of side-effects declined for arthralgia from 4.72 (T-0) to 3.66 (T-1) to 2.76 (T-2), for mucosal dryness from 4.45 (T-0) to 3.65 (T-1) to 2.90 (T-2), for bone pain from 4.74 (T-0) to 3.44 (T-1) to 2.82 (T-2), for hot flushes from 4.97 (T-0) to 3.70 (T-1) to 3.15 (T-2). The reduced severity of the side-effects was statistically significant (p<0.001) for T-1 and T-2, compared to T-0. CONCLUSION: This investigation demonstrates benefits of indication-based complementary treatment with the combination of sodium selenite, proteolytic plant enzymes and Lc-lectin in prostate cancer patients, e.g. reduction of side-effects of HT.

Complementary medicine on side-effects of adjuvant hormone therapy in patients with breast cancer.

BACKGROUND: This clinical investigation was performed in order to evaluate the benefit of complementary medicine in patients with breast cancer undergoing adjuvant hormone therapy (HT). PATIENTS AND METHODS: The patients (n=680) were treated according to international guidelines. All patients suffered from arthralgia and mucosal dryness induced by the adjuvant HT. In order to reduce side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes (bromelaine and papain) and Lens culinaris lectin. On case report formulas, self assessment of defined side-effects of HT (namely arthralgia and mucosal dryness) were documented before and four weeks after complementary treatment. Validation was carried out by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely poor tolerability), however, only patients suffering from severe side-effects (symptom scores >3) were enrolled in this investigation. RESULTS: A total of 64% (316 out of 494) of patients suffering from severe arthralgia and 62% of patients (194 out of 310) with severe mucosal dryness significantly benefited from complementary medicine. The severity of side-effects of HT was reduced by complementary treatment. Mean scores of symptoms declined from 4.92 before treatment to 3.16 after four weeks of treatment for arthralgia and from 4.83 before treatment to 3.21 after four weeks of treatment for mucosal dryness, and these were the primary aims of this investigation. The reduction of side-effects of HT was statistically significant (p<0.001) after four weeks. CONCLUSION: This investigation further demonstrates benefits of indication-based complementary treatment with the combination of sodium selenite, proteolytic enzymes and L. culinaris lectin in patients with breast cancer.

Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany.

AIM: The aim of the study was to evaluate under praxis conditions the safety and efficacy of intravenous (i.v.) vitamin C administration in the first postoperative year of women with breast cancer. PATIENTS AND METHODS: Epidemiological multicentre cohort study, including 15 gynaecologists and general practitioners representatively distributed in Germany. Data from 125 breast cancer patients in UICC stages IIa to IIIb were selected for the study. A total of 53 of these patients were treated with i.v. vitamin C (supplied as Pascorbin® 7.5 g) additional to standard tumour therapy for at least 4 weeks (study group) and 72 without this additional therapy (control group). Main outcome measures were efficacy in regard to outcome and severity of disease- or therapy-induced complaints during adjuvant chemo- and radiotherapy and aftercare. RESULTS: Comparison of control and study groups revealed that i.v. vitamin C administration resulted in a significant reduction of complaints induced by the disease and chemo-/radiotherapy, in particular of nausea, loss of appetite, fatigue, depression, sleep disorders, dizziness and haemorrhagic diathesis. After adjustment for age and baseline conditions (intensity score before adjuvant therapy, chemotherapy, radiotherapy), the overall intensity score of symptoms during adjuvant therapy and aftercare was nearly twice as high in the control group compared to the study group. No side-effects of the i.v. vitamin C administration were documented. DISCUSSION: Oxidative stress and vitamin C deficiency play an important role in the etiology of adverse effects of guideline-based adjuvant chemo-/radiotherapy. Restoring antioxidative capacity by complementary i.v. vitamin C administration helps to prevent or reduce disease-, or therapy-induced complaints in breast cancer patients. CONCLUSION: Complementary treatment of breast cancer patients with i.v. vitamin C was shown to be a well tolerated optimization of standard tumour-destructive therapies, reducing quality of life-related side-effects.

Evidence-based complementary oncology: innovative approaches to optimise standard therapy strategies.

Cancer diseases demand diagnostic and therapeutic measures with proven quality, safety and efficacy. Bases for evaluation of new clinical and therapeutic measures are clinical studies representing level I (randomised controlled trials [RCTs]) or level II (epidemiological cohort studies), in accordance with recommendations of the Centre for Evidence-Based Medicine, University of Oxford, UK. Evidence-based treatment of cancer follows recommendations of international expert panels and includes indication-based surgery, chemotherapy, radiotherapy, hormone and antibody therapy. These therapies have all proven their potency to destroy cancer and their curative feasibility. This review provides an overview of some of the complementary therapies that are also recommended to support and optimise the standard evidence based cancer treatments.

Antimicrobial central venous catheters in oncology: efficacy of a rifampicin-miconazole-releasing catheter.

UNLABELLED: Antimicrobial central venous catheters are discussed as a device to reduce catheter-related infections. Previously we have reported a study with 223 adult surgical patients randomized to receive either a rifampicin-miconazole-loaded central venous catheter (CVC) (n=118) or a standard CVC (n=105). The antimicrobial CVC was shown to reduce catheter colonization (CC) and catheter-related local infection (CRI) significantly even at long-term catheterization. Here, we present further evaluation of the study focusing on possible benefits for high-risk patients. Subgroup analyses showed a pronounced reduction of CC and CRI in male, overweight and oncology patients. Important covariates were skin colonization for CC and oncological disease for CRI. Odds ratio (OR) for reducing CC was 0.076 (95% CI: 0.016-0.360) and CRI was reduced from 26% to 2.3% (p=0.001) in the cancer subgroup. Ex vivo long-term antimicrobial activity of modified catheters exceeded 4 weeks. CONCLUSION: Immunocompromized patients suffering from cancer, transplantation, and dialysis patients with a long-term vascular access may mostly benefit from rifampicin-miconazole-releasing catheters.

Impact of adjuvant chemo- and radiotherapy on the cellular immune system of breast cancer patients.

The relevance of an uncompromised immune system for the development and progress of breast cancer still is a matter of intensive research. The impact of chemo- and/or radiotherapy on peripheral blood immune cell counts and activity of breast cancer patients (n=660) was investigated by flow cytometry. Not only the absolute counts, but also the comparison of those counts with standard values were evaluated. Most studies do not consider this comparison. As compared to pre-treatment values, leukocytes, lymphocytes, B-lymphocytes, T-lymphocytes, helper T-cells and CD25(+) T-cells (activated T-cells) were significantly reduced after chemo- and/or radiotherapy. However, mean cell counts remained within the normal range. Statistically non-significant down-regulation was detected for cytotoxic T-cells, suppressor T-cells and natural killer cells, which are of prime importance as far as tumor development and defence are concerned. The impact of the therapy is not predictable for individual cases. However, only less than 20% of the breast cancer patients were immunocompromized after chemo- and/or radiotherapy.

Evidence-Based Complementary Medicine in Breast Cancer Therapy.

Complementary medicine is currently widely debated by the oncologic community, because the required scientific proof of safety and effectiveness for most of the therapeutic approaches ha s not yet been met with definite results. In the past years, basic research and clinical evaluation of defined complementary therapeutic concepts in oncology have been intensified in an attempt to integrate these procedures into evidence-based medicine. According to definition, scientifically-based therapies of complementary medicine cannot replace the well-studied conventional cancer-destructive therapies such as surgery, chemotherapy, radiotherapy, or hormone therapy. Complementary approaches in oncology that are recommended as an addition to standard cancer-destructive therapies claim to optimize this therapy. A great body of data emerging from scientifically sound clinical trials prove that defined complementary procedures are beneficial for the patients.

Proteolytic enzyme therapy in evidence-based complementary oncology: fact or fiction?

Systemic enzyme therapy was recently subjected to experimental investigations and to rigorous clinical studies in cancer patients. The designs of the relevant clinical cohort studies followed the guidelines of Good Epidemiological Practice and represent level IIB in evidence-based medicine (EBM). Scientifically sound experimental in vitro and in vivo investigations are far advanced and document promising immunological, anti-inflammatory, anti-infectious, and antitumor/antimetastatic activities of proteolytic enzyme mixtures (containing trypsin, chymotrypsin, and papain) or bromelain. EBM level II clinical studies, which are accepted by the European Union to show safety and efficacy of medical treatments, were performed to evaluate the benefit of complementary systemic enzyme therapy in cancer patients suffering from breast and colorectal cancers and plasmacytoma. These studies demonstrated that systemic enzyme therapy significantly decreased tumor-induced and therapy-induced side effects and complaints such as nausea, gastrointestinal complaints, fatigue, weight loss, and restlessness and obviously stabilized the quality of life. For plasmacytoma patients, complementary systemic enzyme therapy was shown to increase the response rates, the duration of remissions, and the overall survival times. These promising data resulted in an "orphan drug status" designation for a systemic enzyme product, which should motivate further studies on this complementary treatment.

Review. Evidence-based complementary oncology. Innovative approaches to optimize standard therapy strategies.

Cancer diseases demand diagnostic and therapeutic measures with proven quality, safety and efficacy. The basis for evaluation is clinical studies representing levels I or II (randomized controlled trials (RCT) or epidemiological cohort studies) in accordance with recommendations of the Centre for Evidence-based Medicine, University of Oxford, UK Regarding these claims, surgery, chemo-, radio- and hormone therapy have emerged as the gold standard in the treatment of carcinomas. These therapies have proven their cancer destructive potencies and their curative feasibilities, dependent on the particular cancer entity and stage. Complementary therapies are recommended to support and optimize the scientifically-based cancer standard treatment. Complementary medicine is currently widely debated by the oncological community, because the required scientific proof of safety and effectiveness for most of the therapeutic approaches has not yet been definitively provided. In the past years, basic research and clinical evaluation of defined complementary therapeutic concepts in oncology have been intensified in an attempt to integrate these procedures into evidence-based medicine. Scientifically-based therapies of complementary medicine cannot replace the well studied conventional cancer-destructive therapies such as surgery, chemo-, radio- or hormone therapy. Accordingly, they are by no means "alternative therapies". Complementary approaches in oncology that are recommended as additional to standard cancer destructive therapies claim to optimize this therapy. A great body of data emerging from scientifically sound clinical trials prove that defined complementary procedures are beneficial for the patients.

Modulation of murine tumor growth and colonization by bromelaine, an extract of the pineapple plant (Ananas comosum L.).

The antitumor and antimetastatic activities of the plant cysteine endoproteinase bromelaine were evaluated in a murine model. Syngeneic sarcoma L-1 cells were incubated with bromelaine (after preceeding time and dosage kinetics) and subcutaneously; (s.c.) or intravenously; (i.v.) inoculated into BALB/c-mice (n = 5 per experimental group) to induce local tumor growth or lung colonization. Compared to non-protease incubated L-1 cells, local tumor growth and experimental lung metastasis decreased significantly (p < 0.05). After bromelaine incubation of the tumor cells. Sarcoma L-1 cells induced local tumor growth after s.c. inoculation and lung colonization after i.v. injection. Intraperitoneal (i.p.) or s.c. administration of bromelaine (optimal dosage and time schedule tested in preceeding kinetic studies) significantly (p < 0.05) reduced local tumor weight, however, lung colonization was non-significantly reduced. Bromelaine incubation of sarcoma L-1 cells significantly reduced their tumorigenic/metastatic capacities. Bromelaine treatment after tumor cell inoculation significantly reduced local tumor growth, experimental lung metastasis, however, to a lesser, non-significant degree.

Comparison of Moraxella catarrhalis isolates from children and adults for growth on modified New York City medium and potential virulence factors.

Initial studies found that Moraxella catarrhalis isolates from adults that grew on modified New York City medium (MNYC(+)) that contained antibiotics selective for pathogenic neisseriae differed from strains that did not grow on this medium (MNYC(-)) in their potential virulence properties. It was predicted that higher usage of antibiotics to treat respiratory illness in children might result in higher proportions of MNYC(+) isolates if antibiotics were an important selective pressure for this phenotype. Two of 100 adult isolates (2 %) were MNYC(+), compared to 88 of 88 isolates (100 %) from children (P = 0.000). MNYC(+) strains were serum-resistant and bound in higher numbers to HEp-2 cells that were infected with respiratory syncytial virus (RSV). Endotoxin from an MNYC(+) isolate induced significantly higher pro-inflammatory response levels than endotoxin from an MNYC(-) strain. MNYC(-) adult isolates expressed haemagglutinins and bound in lower numbers to RSV-infected cells, but serum resistance was variable. All isolates from children were MNYC(+), serum-resistant and bound in greater numbers to RSV-infected cells. These results indicate that both RSV infection and antibiotic usage select for the MNYC(+) phenotype.

Enhancement of circulating dendritic cell activity by immunomodulators (OK432 and KP-40).

The effects of biological response modifiers (BRMs) on the functions of two types of dendritic cells (DCs) were examined in relation to anti-tumor therapy. The two BRMs studied in our assay system were OK432 (a streptococcal preparation) and KP-40 (Propionibacterium avidum: a heat-inactivated bacterial vaccine). Recently, techniques for isolating human DCs from peripheral blood have been established, and DCs can be divided into two subsets: CD11c+ DCs (myeloid DC population) and CD11c- DCs (lymphoid DC population). Both OK432 and KP-40 were found to up-regulate the activity of myeloid-lineage DCs: the expression of major histocompatibility complex (MHC) class II molecules and adhesion/costimulatory molecules increased, and the production of IL-12 also increased. Therefore, DCs pulsed with OK432 and KP-40 could be applied to vaccination as a new adjuvant for specific immunotherapies.

Proinflammatory responses to lipo-oligosaccharide of Neisseria meningitidis immunotype strains in relation to virulence and disease.

Inflammatory responses to lipo-oligosaccharide (LOS) contribute to the severity of meningococcal disease. Strains that express the L(3,7,9) LOS immunotypes are isolated from the majority of patients, but other immunotypes are isolated predominantly from carriers. Inflammatory responses elicited from a human monocytic cell line (THP-1) that had been pretreated with vitamin D3 (VD3) were compared after stimulation with purified LOSs from standard immunotype strains. The neutralizing effects of normal human serum and serum from mice immunized with strain B:2a:P1.5,2:L3 were compared. LOSs of immunotypes L3, L7, L8, and L9 induced significantly higher levels of tumor necrosis factor-alpha and interleukin-6, compared with other immunotypes. Normal human serum neutralized the proinflammatory responses to LOSs of all immunotypes tested. Immune mouse serum neutralized inflammatory responses against LOSs from immunotypes with epitopes cross-reactive with L(3,7,9) moieties. Antibodies found in normal human serum and immune mouse serum to the oligosaccharide, core, and lipid A moieties of meningococcal endotoxin contribute to neutralizing activity.