Fermented Wheat Germ Extract (FWGE) as a Treatment Additive for Castration-Resistant Prostate Cancer: A Pilot Clinical Trial.

Castration-resistant prostate cancer (CRPC) is a devastating and incurable disease. Combined therapy using conventional anticancer drugs and a proprietary medical nutriment, fermented wheat germ extract (FWGE), also known as Avemar, has been suggested as a treatment for progressing prostate cancer (PCa) patients, who have become resistant to first line hormonal therapy (gonadotropin releasing hormone, GnRH). The primary aim of this study was to test if this combined therapy would slow down disease progression in CRPC patients. We tested the nontoxic, readily available, inexpensive FWGE, together with the conventional treatment, GnRH analogue, in 36 CRPC patients. Although this is a pilot study, with the drawback of a statistically small sample size, some anticancer clinical activity of FWGE could be seen in the CRPC patients, as measured by prostate specific antigen doubling time (PSADT). We found that the intake of GnRH with FWGE for at least 4 months, improved the overall health as well as the quality of life (QOL) in 4 patients (11%) and was instrumental in extending the PSADT in about 17 (out of 26) patients (65.4%), six of whom were significant. Since no mentionable adverse events were noticed, this treatment may permit the postponement of chemotherapy for these patients.

Ocular side effects of novel anti-cancer biological therapies.

To examine the ocular side effects of selected biological anti-cancer therapies and the ocular and systemic prognosis of patients receiving them. We retrospectively reviewed all medical records of patients who received biological anti-cancer treatment from 1/2012 to 12/2017 and who were treated at our ocular oncology service. The following data was retrieved: primary malignancy, metastasis, type of biological therapy, ocular side effects, ophthalmic treatment, non-ocular side effects, and ocular and systemic disease prognoses. Twenty-two patients received biological therapies and reported ocular side effects. Eighteen patients (81.8%) had bilateral ocular side effects, including uveitis (40.9%), dry eye (22.7%), and central serous retinopathy (22.7%). One patient (4.5%) had central retinal artery occlusion (CRAO), and one patient (4.5%) had branch retinal vein occlusion (BRVO). At the end of follow-up, 6 patients (27.27%) had resolution of the ocular disease, 13 patients (59.09%) had stable ocular disease, and 3 patients (13.64%) had progression of the ocular disease. Visual acuity improved significantly at the end of follow-up compared to initial values. Eighteen patients (81.8%) were alive at study closure. Biological therapies can cause a wide range of ocular side effects ranging from dry eye symptoms to severe pathologies that may cause ocular morbidity and vision loss, such as uveitis, CRAO and BRVO. All patients receiving biological treatments should be screened by ophthalmologists before treatment, re-screened every 4-6 months during treatment, and again at the end of treatment. Patients on biological treatment who have ocular complaints should be urgently referred to ocular consultation for early identification and early intervention.

Gallium-68 prostate-specific membrane antigen PET-CT and the clinical management of prostate cancer.

OBJECTIVES: The purpose of this study was to evaluate the use of Gallium-68 prostatic-specific membrane antigen (PSMA) PET-computerized tomography (CT) in patients with prostate cancer undergoing imaging for initial staging, biochemical failure or the evaluation of metastatic disease. METHODS: This is a single institution retrospective study of 95 patients with prostate cancer who were referred for PSMA PET-CT scans. The National Comprehensive Cancer Network guidelines were used to generate treatment recommendations. Univariate and multivariate statistical analyses were performed to identify parameters associated with positive findings on a PET-CT PSMA scan. RESULTS: Mean age, Gleason score, and median prostate serum antigen (PSA) were: 72 years, 7.6 and 4 ng/ml, respectively. PSMA PET-CT was positive in 75.5% of the patients. A maximum standardized uptake value was 10.7 ± 8.8. PSMA avidity increased with rising PSA level: PSA ≤ 1 ng/ml: 5/15 patients (33%); PSA 1-5 ng/ml: 18/27 patients (67%), and PSA ≥ 5 ng/ml: 33/34 patients (97%). Following imaging in nine high-risk patients referred for staging, changes in treatment occurred in 6 (67%). Treatment recommendations changed in 27/35 (65%) patients referred due to biochemical failure; these included recurrences suitable for salvage therapy (n = 14), metastatic disease not suitable for salvage therapy (n = 10), and no lesion (n = 17). No changes in treatment occurred in any of the 35 patients referred to evaluate metastatic disease. DISCUSSION: PSMA PET-CT imaging may have a substantial impact on clinical management in prostate cancer patients at the time of initial staging or with biochemical failure; yet this modality does not appear useful in the management of patients with known metastatic disease.

Effect of the botanical formula LCS101 on the anti-cancer effects of radiation therapy.

BACKGROUND AND PURPOSE: The botanical formula LCS101 has been shown in clinical research to reduce chemotherapy-induced toxicities. In pre-clinical research, the formula demonstrated selective anti-cancer effects, in part as a result of radical oxygen species (ROS) activity of the botanical components. The present study examined the interaction between LCS101 and radiation therapy on cancer cell lines. METHODS: Incremental doses of LCS101 were added to breast adenocarcinoma (MCF7), prostate (DU145), transitional cell bladder carcinoma (T24), pancreatic epithelioid carcinoma (PANC-1), and osteosarcoma (U20S) cell lines 4 h after single-dose irradiation (range 0.5-4 Gy). Cell viability was tested using sulforhodamine B (SRB) assay after 1 week, with ROS activity examined using 1 mM of the ROS scavenger sodium pyruvate (ROS scavenger), testing cell viability with an SRB assay. RESULTS: The addition of LCS101 to MCF7 (breast) and DU-145 (prostate) cancer cell lines resulted in a dose-dependent increase in the antiproliferative effects of radiation treatment. The addition of pyruvate inhibited radiation-induced cell death in all of the cell lines treated with LCS101. CONCLUSIONS: The addition of the botanical formula LCS101 to irradiated cancer cells results in an apparent additive effect, most likely through a ROS-mediated mechanism. These findings support the use of LCS101 by patients undergoing radiation therapy, for both its clinical as well as anti-cancer effects.

Botanical Formula LCS101: A Multi-Targeted Approach to Cancer Care.

BACKGROUND AND PURPOSE: LCS101 is a botanical formula extracted from 14 botanical components. While conventional oncology focuses on targeted medicine, research on LCS101 adopts a multi-targeted approach, examining its preclinical (in vitro, in vivo, and ex vivo) and clinical (randomized controlled trial, pragmatic) effects. This includes examining the formula's impact on the immune system, selective anticancer effects, and improved chemotherapy-related symptoms and quality of life. Effects on the Immune System: In murine splenic cell cultures, LCS101 significantly increased T-cell proliferation and macrophage tumor necrosis factor-α production. Blood samples from healthy volunteers exposed to LCS101 showed a dose-dependent increase in natural killer cell activity; and a randomized controlled trial showed significantly lower rates of leucopenia/neutropenia and anemia in patients with breast cancer undergoing chemotherapy. Selective Anticancer Effects: In vitro LCS101 demonstrated selective growth inhibition (on XTT viability assay) in human breast and prostate cancer cell lines, without any harmful effects on normal human epithelial cells. The anticancer effects were attributed to reactive oxygen species activity. Cytotoxic effects of doxorubicin and 5-fluorouracil on breast cancer cell lines were significantly increased following exposure to LCS101, with a protective effect in normal cells. Symptom Relief and Quality of Life: Clinical research shows that patients taking LCS101 during chemotherapy are less likely to report symptoms such as fatigue, pain, nausea and vomiting. CONCLUSION: LCS101 exhibits multi-targeted effects, with significant implications for cancer care. Further research is needed to better understand the impact of these findings.

Feasibility of Homeopathic Treatment for Symptom Reduction in an Integrative Oncology Service.

BACKGROUND: Homeopathy has the potential to reduce symptoms related to cancer treatment. The present study examined the feasibility of a homeopathic consultation and treatment program, provided as part of an integrative oncology service. METHODS: The electronic medical files of patients undergoing a homeopathic consultation in an integrative oncology service clinic were examined retrospectively. Adherence to the homeopathic treatment regimen and perceived response to the treatment were evaluated. RESULTS: The files of 124 patient (34 males, 90 females) were examined, of which two-thirds reported acquiring and self-administering the homeopathic remedy as prescribed, and nearly three-quarters reporting a beneficial effect. Adherence to the homeopathic treatment regimen was greatest among patients attending a second visit, as opposed to having only telephone/e-mail follow-up ( P < .005). An association was found between a perceived beneficial effect of treatment with attending a follow-up visit ( P = .04), female gender ( P = .02), younger age ( P = .048), diagnosis of breast cancer ( P = .014), and current radiation treatment (vs chemotherapy; P = .003). Patients reporting chemotherapy-induced peripheral neuropathy were also more likely to report a beneficial effect ( P = .004), as were female patients reporting hot flashes ( P = .005) and those referred by an oncologist ( P = .046). No adverse effects were attributed to the homeopathic treatment. CONCLUSIONS: Homeopathy can be successfully incorporated within a supportive care integrative oncology service. In addition to demographic and cancer-related characteristics, as well as symptoms, patients attending a second visit (vs only telephone/e-mail follow-up) were more likely to adhere to and perceive a beneficial effect from the homeopathic regimen.

Unmonitored use of herbal medicine by patients with breast cancer: reframing expectations.

PURPOSE: To identify the unmonitored use of herbal medicine by female patients with breast cancer, examining the impact of an integrative physician (IP) consultation on this practice. METHODS: The files of 269 female patients with breast cancer following an IP consultation were surveyed retrospectively for use of herbal medicine for cancer-related goals. Expectations from the IP consultation and adherence to the IP-guided treatments were examined as well. RESULTS: Among the cohort, 111 (41.3%) reported using herbal medicine for cancer-related goals, unmonitored by their oncology healthcare professional. Factors predicting herbal medicine use were the adoption of dietary changes (odds ratio = 13.6, p < 0.001, CI 7.16-26.0) and the expectation that the IP consultation and treatments would address cancer-related goals (odds ratio = 3.29, p = 0.001, CI 1.64-6.6). Patients with metastatic disease were more likely to be using herbal medicine than non-users (34.5 vs. 22.8%; p = 0.088), as were those who had consulted with a complementary/alternative medicine practitioner (54.9 vs. 20.8%; p = 0.005). The IP advised 17 patients (15.3%) to stop taking specific herbal products due to safety-related concerns; and 10 patients to take dietary supplements for relief of specific symptoms. Herbal medicine users were less likely than non-users to adhere to the IP-recommended treatment program (34.7 vs. 48.3%; p = 0.037). CONCLUSIONS: Unmonitored use of herbal medicine by patients with breast cancer is more frequent among those adopting dietary changes for cancer-related goals. Integrative physicians provide evidence-based guidance on the safe and effective use of herbal products, and reframe patient expectations from cancer-related goals to reducing symptoms and improving quality of life.

Classifying high-risk versus very high-risk prostate cancer: is it relevant to outcomes of conformal radiotherapy and androgen deprivation?

OBJECTIVE: To evaluate outcomes in prostate cancer patients classified as high-risk (HR) or very high-risk (VHR) who were treated with conformal radiation therapy (CRT) and androgen deprivation therapy (ADT). METHODS: Between 11/2001 and 3/2012, 203 patients with HR disease received CRT to the prostate (78-82 Gy) and pelvic lymph nodes (46-50 Gy) with ADT (6 m-2 years). Median follow-up was 50 months (12 m-142 m). Biochemical failure was defined according to Phoenix definition. Imaging studies were used to identify local, regional or metastatic failure. Four different VHR/HR groupings were formed using the 2014 and revised 2015 NCCN guidelines. Differences were examined using Kaplan Meier (KM) estimates with log rank test and uni- and multivariate Cox regression analysis (MVA). RESULTS: Failure occurred in 30/203 patients (15%). Median time to failure was 30 m (4 m-76 m). KM estimate of 4 year biochemical disease free survival (b-DFS) for the entire cohort was 87% (95%CI: 82-92%). Four year KM survival estimates for b-DFS, PCSS and OS were comparable for each NCCN subgroup. On univariate analysis, the NCCN subgroups were not predictive of b-DFS at 4 years, however, DMFS was worse for both VHR subgroups (p = .03and .01) respectively. Cox univariate analysis was also significant for: PSA ≥40 ng/ml p = 0.001; clinical stages T2c p = .004, T3b p = .02 and > 4 cores with Gleason score 8-10 p < .03. On MVA, only PSA ≥ 40 ng/ml was predictive for b-DFS or MFS at 4 years (HR: 3.75 and 3.25, p < 0.005). CONCLUSION: Patients with HR and VHR disease treated with CRT and ADT had good outcomes. Stratification into HR and VHR sub-groups provided no predictive value. Only PSA ≥40 ng/ml predicted poor outcomes on MVA. Distant failure was dominant and local recurrence rare, suggesting that improved systemic treatment rather than intensification of local therapy is needed. Patients with high-risk prostate cancer are most often treated with conformal dose escalated radiation therapy with androgen deprivation. Stratification into high versus very high-risk subgroups using 2014 or revised 2015 National Comprehensive Cancer Network (NCCN) criteria did not impact treatment outcomes. Only Prostate Serum Antigen (PSA) ≥40 ng/ml was predictive of poor prognosis. Distant failure was dominant and local recurrence uncommon which challenges the notion that intensification of local therapy will further improve outcomes in patients with high-risk disease.

Selective anticancer effects and protection from chemotherapy by the botanical compound LCS101: Implications for cancer treatment.

There is a need for new options for reducing the side effects of cancer treatment, without compromising efficacy, enabling patients to complete treatment regimens. The botanical compound LCS101 exhibits inhibitory effects on cancer cell growth, and reduces chemotherapy-induced hematological toxicities. The aim of the present study is to examine the selectivity of the effects of the compound, alone and in conjunction with conventional chemotherapy agents, on cancer cell proliferation. The effects of LCS101 were tested on a number of cancer cell lines (breast, MCF7, MDA-MB­231; colorectal, HCT116; prostate, PC-3, DU-145) and on non-tumorigenic normal human epithelial cells (breast, MCF10A; prostate, EP#2). Cell viability was analyzed using an XTT assay and observed by light microscopy. Necrosis and apoptosis were examined using FACS analysis and immunoblotting. LCS101 selectively induced cell death in breast, colon and prostate cancer cell lines, as measured by XTT assay. Light microscopy and FACS analysis showed changes indicative of a necrotic process. LCS101 was also found to induce PARP-1 reduction in breast cancer cells, with no effect on non-tumorigenic breast epithelial cells. While LCS101 increased cell death in cancer cells exposed to doxorubicin and 5-FU, it showed a protective effect on non-tumorigenic human epithelial cells from chemotherapy-induced cell death. A similar selective effect was observed with apoptosis-associated PARP-1 cleavage. The findings demonstrate that the anti-proliferative effects exhibited by the botanical compound LCS101 are selective to cancer cells, and offer protection to non-tumorigenic normal epithelial cells from chemotherapy agents.