The Role of Grape Seed Extract in the Treatment of Chemo/Radiotherapy Induced Toxicity: A Systematic Review of Preclinical Studies.

Grapes are one of the most consumed fruits in the world and are rich in polyphenols. Grape seed proanthocyanidins (GSP) have demonstrated chemopreventive and/or chemotherapeutic effects in various cancer cell cultures and animal models. The clinical efficacy of chemotherapy is often limited by its adverse effects. Several studies show that reactive oxygen species mediate the cardiotoxicity and neurotoxicity induced by various cancer chemotherapeutic agents. This implies that concomitant administration of antioxidants may prevent these adverse effects. The review was carried out in accordance with the PRISMA guidelines. An electronic search strategy in Medline and Embase databases was conducted. Of the 41 studies reviewed, 27 studied GSP while the remainder (14) studied grape seed or skin extracts (GSE). All the studies were published in English, except 2 in Chinese. A significant percentage (34%) of the studies we reviewed assessed the effect of GSE or GSP on cardiotoxicity induced by chemotherapy. Doxorubicin was the most common chemotherapeutic drug studied followed by cisplatin. Research studies that assessed the effect of GSE or GSP on radiation treatment accounted for 22% of the articles reviewed. GSE/GSP ameliorates some of the cytotoxic effects on normal cells/tissues induced by chemo/radiotherapy.

National Institutes of Health psilocybin research speaker series: State of the science, regulatory and policy landscape, research gaps, and opportunities.

The U.S. National Institutes of Health (NIH) convened a seminal first ever psychedelic drug substance-focused speaker series, from April 22 to June 10, 2021, titled the "NIH Psilocybin Research Speaker Series." This speaker series provided evidence-based scientific information to the public and the scientific community. Its aims were to assess the current state of the science, the regulatory and policy landscape, as well as to identify gaps in knowledge and understanding, ultimately serving to define future research needs. The highlights of the lectures and discussion from 26 national and international distinguished experts served as the basis for this Special Issue of Neuropharmacology. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

Are psychedelic medicines the reset for chronic pain? Preliminary findings and research needs.

Chronic pain is a leading cause of disability, reduced productivity, healthcare seeking behavior, and a contributor to opioid overdose in the United States. For many people, pain can be satisfactorily managed by existing medicines and comprehensive psychosocial treatments. For others, available treatments are either ineffective or not acceptable, due to side effects and concerns about risks. Preliminary evidence suggests that some psychedelics may be effective for certain types of pain and/or improved quality of life with increased functionality and reduced disability and distress in people whose pain may never be completely relieved. Efficacy in these quality-of-life related outcomes would be consistent with the 'reset in thinking' about chronic pain management being increasingly called for as a more realistic goal for some people as compared to complete elimination of pain. This commentary summarizes the rationale for conducting more basic research and clinical trials to further explore the potential for psychedelics in chronic pain management. Additionally, if shown to be effective, to then determine whether the effects of psychedelics are primarily due to direct antinociceptive or anti-inflammatory mechanisms, or via increased tolerability, acceptance, and sense of spirituality, that appear to at least partially mediate the therapeutic effects of psychedelics observed in psychiatric disorders such as major depression. This commentary represents a collaboration of clinical and more basic scientists examining these issues and developing recommendations for research ranging from neuropharmacology to the biopsychosocial treatment factors that appear to be as important in pain management as in depression and other disorders in which psychedelic medicines are under development. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

Psychedelic drug abuse potential assessment research for new drug applications and Controlled Substances Act scheduling.

New medicines containing classic hallucinogenic and entactogenic psychedelic substance are under development for various psychiatric and neurological disorders. Many of these, including psilocybin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are Schedule I controlled substances of the United States Controlled Substances Act (US CSA), and similarly controlled globally. The implications of the CSA for research and medicines development, the path to approval of medicines, and their subsequent removal from Schedule I in the US are discussed. This entire process occurs within the framework of the CSA in the US and its counterparts internationally in accordance with international drug control treaties. Abuse potential related research in the US informs the eight factors of the CSA which provide the basis for rescheduling actions that must occur upon approval of a drug that contains a Schedule I substance. Abuse-related research also informs drug product labeling and the risk evaluation and mitigation strategies (REMS) will likely be required for approved medicines. Human abuse potential studies typically employed in CNS drug development may be problematic for substances with strong hallucinogenic effects such as psilocybin, and alternative strategies are discussed. Implications for research, medicinal development, and controlled substance scheduling are presented in the context of the US CSA and FDA requirements with implications for global regulation. We also discuss how abuse-related research can contribute to understanding mechanisms of action and therapeutic effects as well as the totality of the effects of the drugs on the brain, behavior, mood, and the constructs of spirituality and consciousness.

The National Cancer Institute's Conference on Acupuncture for Symptom Management in Oncology: State of the Science, Evidence, and Research Gaps.

The Division of Cancer Treatment and Diagnosis, Office of Cancer Complementary and Alternative Medicine, at the National Cancer Institute (NCI) held a symposium on "Acupuncture for Cancer Symptom Management" on June 16 and 17, 2016. Invited speakers included 19 scientists and scholars with expertise in acupuncture and cancer research from the United States, Europe, and China. The conference reviewed the NCI's grant funding on acupuncture, analyzed the needs of cancer patients, reviewed safety issues, and assessed both the current scientific evidence and research gaps of acupuncture in oncology care. Researchers and stakeholders presented and discussed basic mechanisms of acupuncture; clinical evidence for specific symptoms; and methodological challenges such as placebo effects, novel biostatistical methods, patient-reported outcomes, and comparative effectiveness research. This paper, resulting from the conference, summarizes both the current state of the science and clinical evidence of oncology acupuncture, identifies key scientific gaps, and makes recommendations for future research to increase understanding of both the mechanisms and effects of acupuncture for cancer symptom management.

A phase II trial of neoadjuvant docetaxel and capecitabine for locally advanced breast cancer.

PURPOSE: This study evaluated the toxicity and efficacy of docetaxel/capecitabine as neoadjuvant treatment for stage 2/3 breast cancer. EXPERIMENTAL DESIGN: Subjects with newly diagnosed invasive stage 2 and 3 breast cancer were eligible. The first cohort of patients was treated at dose A with neoadjuvant docetaxel (75 mg/m(2) i.v. day 1) and capecitabine (1000 mg/m(2) orally twice daily days 2-15) for four cycles. A second cohort of subjects was treated with a reduced dose, dose B, of docetaxel (60 mg/m(2) i.v. day 1) and capecitabine (937.5 mg/m(2) orally twice daily days 2-15). RESULTS: Thirty patients were enrolled. Eight of 10 patients treated at dose A required dose reductions of either docetaxel or capecitabine secondary to grade 3 or 4 toxicities: mucositis (1), hand-foot syndrome (3), diarrhea (2), perirectal abscess (1), and neutropenia (2). Because of a high rate of dose reductions, the next 20 patients were treated at dose B. The mean cumulative administered dose of docetaxel was 285 and 231 mg/m(2) at dose A and dose B, respectively. For capecitabine, the mean cumulative dose at dose A and B were similar at 1585 and 1627 mg/m(2)/day, respectively. The overall clinical response rate was 90% with 31% of patients having a complete response and 59% having a partial response. A pathological complete response in the breast was achieved in 10% of patients after four cycles of docetaxel/capecitabine. CONCLUSIONS: Docetaxel/capecitabine is a highly active regimen in the neoadjuvant setting. Neoadjuvant therapy with 75 mg/m(2) docetaxel and 1600 mg/m(2)/day days 2-15 is recommended.

Complementary and Alternative Medicine Use Among Overweight and Obese Cancer Survivors in the United States.

PURPOSE: The purpose of the study was to determine the prevalence of complementary and alternative medicine (CAM) use among US cancer survivors; examine whether use varies by underweight/normal weight, overweight, and obese body mass index status; determine reasons for use; and document disclosure rates of CAM use to medical professionals. METHODS: Data for 1785 cancer survivors were obtained from the 2007 National Health Interview Survey and CAM supplement. The prevalence and associations of CAM use in the previous 12 months were compared among underweight/normal weight, overweight, and obese adult cancer survivors. RESULTS: Nearly 90% of cancer survivors used at least one type of CAM therapy in the 12 months preceding the survey. Those who were overweight, but not obese, were more likely to use a CAM modality compared to normal/underweight respondents. Over two thirds (71%) reported using CAM therapy for general health and wellness and 39.3% used CAM because a health care provider recommended it. Disclosure rates of CAM use to conventional medical professionals varied widely by CAM modality. CONCLUSIONS: An overwhelming majority of US cancer survivors use CAM for a variety of reasons. Overweight cancer survivors may be more likely to use CAM than those who are underweight, normal weight, or obese. Cancer survivors should be screened by medical providers for the use of CAM therapies; furthermore, prospective clinical research evaluating the efficacy and safety of biologically based CAM therapies, often used by cancer survivors, is important and necessary for the well-being of this population.

The National Cancer Institute best case series program: a summary of cases of cancer patients treated with unconventional therapies in India.

OBJECTIVES: The National Cancer Institute (NCI) Best Case Series (BCS) Program provides an independent review of medical records, imaging, and pathology of cancer patients treated with unconventional therapies. The goal of the NCI BCS Program is to identify preliminary evidence of tumor regression and assess whether there is sufficient evidence to move forward with NCI-initiated research. The objective was to review case reports submitted by 4 practitioners from India who used ayurvedic and homeopathic therapies to treat cancer. DESIGN: Retrospective review of case reports of 4 practitioners from India who used ayurvedic and homeopathic therapies to treat cancer. RESULTS: A total of 68 cases were submitted to the NCI BCS Program. Fifty-one percent of the cases represented homeopathy and 49% ayurveda. Of the 68 cases, 32 (47%) of the cases were collectively designated as "persuasive" (P) or "supportive"(S), and 36 (53%) as "not evaluable." Forty-one (60%) patients did not have any prior conventional treatment. CONCLUSION: The challenge for submitters rests in their ability to supply sufficient documentation for the NCI BCS Program. The NCI BCS Program represents a unique avenue for the rigorous evaluation of "best cases" to identify complementary and alternative medicine modalities that are promising for prospective preclinical evaluation or prospective research.

Survey of complementary and alternative medicine practitioners regarding cancer management and research.

The primary purpose of this survey was to assess the interest and concerns of a group of cancer complementary and alternative medicine (CAM) practitioners regarding CAM research issues. These issues include the CAM modalities used most often by CAM practitioners in the treatment of cancer patients, cancer CAM practitioners' perceptions of the most promising areas of cancer CAM research, the perceived obstacles to carrying out research objectives in the emerging field of cancer CAM research, the extent of awareness of the National Cancer Institute (NCI) Best Case Series Program, and CAM practitioners' level of interest in research collaboration with CAM researchers. A cross-sectional survey of a convenience sample of cancer CAM practitioners was conducted. One hundred thirty-four respondents completed the survey. About 72% of the respondents were involved in the care of cancer patients, and these were considered the informative respondents. All results were from the informative respondent group. Respondent practitioners provided care using interventions from all seven of the predefined CAM categories. This care was provided to improve both quality of life and survival. Over two-thirds of the respondents rated research in pharmacologic and biologic treatments, alternative medical systems and nutritional therapeutics for cancer treatment, and symptom/side-effect management as high-priority areas. Although no single obstacle to research predominated as the most significant, the most frequently encountered obstacle was lack of awareness of appropriate funding sources (75.4%). More than 83% of respondents expressed some interest in or willingness to establish research collaboration with a cancer researcher. The results from this survey indicate that many cancer CAM practitioners have shared interests, perceived obstacles, and desired research opportunities. Despite a small sample size and lack of a feasible process for random sampling, this survey highlights avenues to promote and support collaborative research. The NCI/Office of Cancer Complementary and Alternative Medicine will continue to respond to the concerns elucidated by the survey by developing strategies for future program opportunities within the NCI.