Integrative Cancer Therapies

The heart of evidence-based practice is in fact to be found in the use of evidence gained from systematic reviews or more correctly in the synthesis of evidence from systematic reviews. But just as studies vary in the quality of the design so do systematic reviews, and it is therefore necessary for those wishing to make clinical decisions based on this evidence to evaluate the evidence summaries and synthesis themselves. This article examines the criteria available for evaluating the quality of the evidence summary and synthesis. It provides a set of questions for doing this: who did the review; w hat was the objective of the review; how was the review done? Together these questions allow us to determine the trustworthiness of the review. However, that by itself is insufficient for making clinical decisions. The article suggests that this occurs because the very studies that improve the quality of reviews, that is, the randomized controlled trials, deal with efficacy and not effectiveness. Because they tend to be conducted under ideal conditions, they seldom provide the type of information needed to make a decision vis-à-vis an individual patient. The article suggests that observation studies provide much better information in this regard. The challenge here, however, is to develop standards for judging quality observation studies. In conclusion, systematic reviews and syntheses of evidence are a necessary but an insufficient method for making clinical decisions.

Because cancer care is presently developing into a complicated network of interventions delivered at different times and places with different intentions, there is a need to consider whether the current research approaches in clinical cancer care adequately cover the ongoing treatment choices and combinations. Researchers in complementary and alternative medicine (CAM) are proposing whole systems research as an additional research approach for modern systems of care, whether they include complementary and alternative medicine or not. The current status of whole systems research methodology development is mainly theoretical. Necessary components of the methodology include focus on interventions, context, process, outcomes, and philosophy. Further development should be based on observational studies using both qualitative and quantitative approaches, often combined. Only when modern healthseeking systems of treatment behaviors are thoroughly understood should fine-tuning of hypothesis-testing research methods be continued.

This article summarizes a network and complex systems science model for research on whole systems of complementary and alternative medicine (CAM) such as homeopathy and traditional Chinese medicine. The holistic concepts of networks and nonlinear dynamical complex systems are well matched to the global and interactive perspectives of whole systems of CAM, whereas the reductionistic science model is well matched to the isolated local organ, cell, and molecular mechanistic perspectives of pharmaceutically based biomedicine. Whole systems of CAM are not drugs with specific actions. The diagnostic and therapeutic approaches of whole systems of CAM produce effects that involve global and patterned shifts across multiple subsystems of the person as a whole. For homeopathy, several characteristics of complex systems, including the probabilistic nature of attractor patterns, variable sensitivity of complex systems to initial conditions, and emergent behaviors in the evolution of a system in its full environmental context over time, could help account for the mixed basic science and controlled clinical trial research findings, in contrast with the consistently positive outcomes of observational studies in the literature. Application of theories and methods from complex systems and network science can open a new era of advances in understanding factors that lead to good versus poor individual global outcome patterns and to rational triage of patients to one type of care over another. The growing reliance on complex systems thinking and systems biology for cancer research affords a unique opportunity to bridge between the CAM and conventional medical worlds with some common language and conceptual models.

Acupuncture care delivered pragmatically as an adjunct to conventional care may lead to improvements in quality of life and alleviation of conventional treatment-related side effects among breast cancer patients. Patient perceptions and expectations of treatment and the therapeutic relationship inherent to acupuncture care could modify treatment effects. The aim of this study was to design a rigorous feasibility study in preparation for trial to evaluate the effects of acupuncture care (a whole system) on the fatigue experienced by patients undergoing conventional treatment of their breast cancer. Phase 1 included the development of a treatment protocol for a short course of acupuncture care for patients with breast cancer undergoing chemotherapy. Defining best practice in this context will ensure that the intervention tested will have meaning and validity for all professional acupuncturists. Phase 2 will be a randomized feasibility pilot study using the acupuncture treatment protocol for 40 patients with breast cancer undergoing chemotherapy. The study will use a mixed-methods approach involving both qualitative and quantitative assessments. Outcome assessment will include validated measures for fatigue, quality of life, and depression. The proposed study will tell us what effects of acupuncture care are important to the patient and address acupuncture as it is practiced in the real world. Results from this study will enable a definitive randomized controlled trial to evaluate the effectiveness of acupuncture care for fatigue in breast cancer patients undergoing chemotherapy.

For more than 200 years, biomedicine has approached the treatment of disease by studying disease processes (patho-genesis), inferring causal connections and developing specific approaches for therapeutically interfering with those processes. This pathogenic approach has been highly successful in acute and traumatic disease but less successful in chronic disease, primarily because of the complex, multi-factorial nature of most chronic disease, which does not allow for simple causal inference or for simple therapeutic interventions. This article suggests that chronic disease is best approached by enhancing healing processes (salutogenesis) as a whole system. Because of the nature of complex systems in chronic disease, an evaluation model based on integrative medicine is felt to be more appropriate than a disease model. The authors propose and describe an integrated model for the evaluation of healing (IMEH) that collects multilevel “thick case” observational data in assessing complex practices for chronic disease. If successful, this approach could become a blueprint for studying healing capacity in whole medical systems, including complementary medicine, traditional medicine, and conventional primary care. In addition, streamlining data collection and applying rapid informatics management might allow for such data to be used in guiding clinical practice. The IMEH involves collection, integration, and potentially feedback of relevant variables in the following areas: (1) sociocultural, (2) psychological and behavioral, (3) clinical (diagnosis based), and (4) biological. Evaluation and integration of these components would involve specialized research teams that feed their data into a single data management and information analysis center. These data can then be subjected to descriptive and pathway analysis providing “bench and bedside” information.

Homeopathy is a holistic method of treatment that uses ultralow doses of highly diluted natural substances originating from plants, minerals, or animals and is based on the principle of “like cures like.” Despite being occasionally challenged for its scientific validity and mechanism of action, homeopathy continues to enjoy the confidence of millions of patients around the world who opt for this mode of treatment. Contrary to skeptics' views, research on home-opathy using modern tools mostly tends to support its efficacy and advocates new ideas toward understanding its mechanism of action. As part of a Point-Counterpoint feature, this review and its companion piece in this issue by Moffett et al (Integr Cancer Ther. 2006;5:333-342) are composed of a thesis section, a response section in reaction to the companion thesis, and a rebuttal section to address issues raised in the companion response.

Alternative medical approaches to human diseases such as cancer are becoming increasingly popular, but reports on their success rates have been highly variable. Homeopathy is an alternative medical practice often applied to less critical human diseases but one that has also been applied sporadically to the treatment of cancer. Animal studies on the use of homeopathy to treat experimental cancer are few and the evidence provided to date is far from conclusive. The debate presented here concerns the utility of animal studies on cancer treatment with homeopathic preparations. As part of a Point-Counterpoint feature, this review and its companion piece in this issue by Khuda-Bukhsh (Integr Cancer Ther. 2006;5:320-332) are composed of a thesis section, a response section in reaction to the companion thesis, and a rebuttal section to address issues raised in the companion response.

Background: Homeopathy is a complementary medicine widely used around the world. Despite extensive use of homeopathy for cancer and other serious conditions with reported success, clinical and laboratory research has been equivocal, and no rigorous research has been done on cancer. In 1999, the US National Cancer Institute evaluated the effects of homeopathic treatment of cancer from a clinic in India and has released a request for protocols to conduct further research into this treatment. Therefore, the authors conducted a series of carefully controlled laboratory studies evaluating the effects of commonly used homeopathic remedies in cell and animal models of prostate cancer. Study Design: One hundred male Copenhagen rats were randomly assigned to either treatment or control groups after inoculation with prostate tumor cells. Methods: Prostate tumor cells DU-145, LNCaP, and MAT-LyLu were exposed to 5 homeopathic remedies. Male Copenhagen rats were injected with MAT-LyLu cells and exposed to the same homeopathic remedies for 5 weeks. In vitro outcomes included tumor cell viability and apoptosis gene expression. In vivo outcomes included tumor incidence, volume, weight, total mortality, proliferating cell nuclear antigen (PCNA) expression, apoptotic cell death (terminal deoxynucleotidyl transferase mediated d-uridine triphosphate nick end labeling), and gene expression (rAPO-multiprobe). Results: There were no effects on cell viability or gene expression in 3 prostate cell lines with any remedies at any exposure time. There was a 23% reduction in tumor incidence (P < .0001), and for animals with tumors, there was a 38% reduction in tumor volume in homeopathy-treated animals versus controls (P < .02). At time of killing, experimental animals with tumors had a 13% lower average tumor weight (P < .05). Tumors in these treated animals showed a 19% increase in apoptotic cell death (P < .05) and reduced PCNA-positive cells. Conclusions: The findings indicate that selected homeopathic remedies for the present study have no direct cellular anticancer effects but appear to significantly slow the progression of cancer and reduce cancer incidence and mortality in Copenhagen rats injected with MAT-LyLu prostate cancer cells.

Background: Increasing evidence suggests that the inability to undergo apoptosis is an important factor in the development and progression of prostate cancer. Agents that induce apoptosis may inhibit tumor growth and provide therapeutic benefit. In a recent study, the authors found that certain homeopathic treatments produced anticancer effects in an animal model. In this study, the authors examined the immunomodulating and apoptotic effects of these remedies. Materials and Methods: The authors investigated the effect of a homeopathic treatment regimen containing Conium maculatum, Sabal serrulata, Thuja occidentalis, and a MAT-LyLu Carcinosin nosode on the expression of cytokines and genes that regulate apoptosis. This was assessed in prostate cancer tissues, extracted from animals responsive to these drugs, using ribonuclease protection assay or reverse transcription polymerase chain reaction. Results: There were no significant changes in mRNA levels of the apoptotic genes bax, bcl-2, bcl-x, caspase-1, caspase-2, caspase-3, Fas, FasL, or the cytokines interleukin (IL)–1α, IL-1β, tumor necrosis factor (TNF)–β, IL-3, IL-4, IL-5, IL-6, IL-10, TNF-α, IL-2, and interferon-γ in prostate tumor and lung metastasis after treatment with homeopathic medicines. Conclusions: This study indicates that treatment with the highly diluted homeopathic remedies does not alter the gene expression in primary prostate tumors or in lung metastasis. The therapeutic effect of homeopathic treatments observed in the in vivo experiments cannot be explained by mechanisms based on distinct alterations in gene expression related to apoptosis or cytokines. Future research should explore subtle modulations in the expression of multiple genes in different biological pathways.

Background: Homeopathy is an alternative medical system practiced in all parts of the world. Although several theories are proposed to explain the mechanisms of action, none are scientifically verified. In this study, the authors investigate the effect of selected homeopathic remedies often used to treat prostate and breast cancer. Materials and Methods: The authors investigated the effect of the homeopathic medicines Conium maculatum, Sabal serrulata, Thuja occidentalis, Asterias, Phytolacca, and Carcinosin on prostate and breast cancer cell (DU-145, LNCaP, MAT-LyLu, MDA-MB-231) growth and on gene expression that regulates apoptosis, using MTT and multiprobe ribonuclease protection assay. Results: None of the homeopathic remedies tested in different potencies produced significant inhibitory or growth-promoting activity in either prostate or breast cancer cells. Also, gene expression studies by ribonuclease protection assay produced no significant changes in mRNA levels of bax, bcl-2, bcl-x, caspase-1, caspase-2, caspase-3, Fas, or FasL after treatment with homeopathic medicines. Conclusions: The results demonstrate that the highly diluted homeopathic remedies used by homeopathic practitioners for cancer show no measurable effects on cell growth or gene expression in vitro using currently available methodologies.

The use of dietary supplements for various ailments enjoys unprecedented popularity. As part of this trend, Sabal serrulata (saw palmetto) constitutes the complementary treatment of choice with regard to prostate health. In homeopathy, Sabal serrulata is commonly prescribed for prostate problems ranging from benign prostatic hyperplasia to prostate cancer. The authors' work assessed the antiproliferative effects of homeopathic preparations of Sabal serrulata, Thuja occidentalis, and Conium maculatum, in vivo, on nude mouse xenografts, and in vitro, on PC-3 and DU-145 human prostate cancer as well as MDA-MB-231 human breast cancer cell lines. Treatment with Sabal serrulata in vitro resulted in a 33% decrease of PC-3 cell proliferation at 72 hours and a 23% reduction of DU-145 cell proliferation at 24 hours (P<.01). The difference in reduction is likely due to the specific doubling time of each cell line. No effect was observed on MDA-MB-231 human breast cancer cells. Thuja occidentalis and Conium maculatum did not have any effect on human prostate cancer cell proliferation. In vivo, prostate tumor xenograft size was significantly reduced in Sabal serrulata–treated mice compared to untreated controls (P=.012). No effect was observed on breast tumor growth. Our study clearly demonstrates a biologic response to homeopathic treatment as manifested by cell proliferation and tumor growth. This biologic effect was (i)significantly stronger to Sabal serrulata than to controls and (ii)specific to human prostate cancer. Sabal serrulata should thus be further investigated as a specific homeopathic remedy for prostate pathology.

Introduction: This report describes the case of a male patient with pituitary macroadenoma treated with the artemisinin analog artemether. Patient and Methods: A 75 year-old male patient presented with vision, hearing, and locomotion-related problems. Artemether was administered orally to the patient over a period of 12 months. Results: Although the tumor remained consistent in size, CT scan shows a reduction in its density, and clinically, the related symptoms and signs resolved significantly as therapy progressed. Discussion: Overall, the artemether treatment was beneficial in improving the patient's quality of life. Artemether and other artemisinin analogs offer promise for cancer therapy.

Five-year survival of patients with stage IV epithelial ovarian carcinoma not treated after recurrence is almost non-existent in oncological literature. The authors report a patient almost 30 years after surgery of the primary epithelial ovarian carcinoma lesion and 15 years after recurrent disease and incomplete chemotherapy who is alive without evidence of disease. She received no conventional oncological therapy during the past 15 years but rather used many types of alternative medicine, predominantly mind body therapies. The authors review the relevant literature on this subject and describe what they believe to be the first report of long-term survival of such a patient.