Therapeutic effects of regorafenib after sorafenib monotherapy with advanced hepatocellular carcinoma including Child-Pugh classification B: A retrospective observational study.

The therapeutic effect of regorafenib was previously demonstrated in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh classification A (CP-A) whose disease progressed during sorafenib treatment in a phase III trial. However, treatment options are limited for patients with advanced HCC other than CP-A. In this study, we aimed to evaluate the therapeutic effect of regorafenib on advanced HCC patients including those with Child-Pugh classification B (CP-B).We retrospectively analyzed the medical records of 21 patients with advanced HCC who were treated with regorafenib after sorafenib monotherapy at our hospital from July 2017 to April 2018 and were followed up until September 2019. Patients were classified according to liver function and adverse events experienced during sorafenib treatment and were started on regorafenib with a pre-defined reduced starting dose along with a dose reduction and schedule change based on the judgement of the attending physician.At regorafenib initiation, 13 and 8 patients were classified as CP-A and CP-B, respectively. In all patients with CP-B, the starting dose of regorafenib was reduced, and the pre-defined starting-dose sets were applied to 17 (81%) patients. The median duration of regorafenib treatment in patients with CP-A and CP-B were 4.1 months and 2.0 months, respectively, with no significant difference. The median overall survival from regorafenib initiation (OS-r) and sorafenib initiation (OS-s) was 13.2 months and 30.9 months, respectively. In subgroup analysis, OS-r was 16.3 months in patients with CP-A and 10.1 months with CP-B with no significant difference (P = .44), whereas OS-r was 16.3 months in patients with modified albumin-bilirubin Grade 1/2a and 13.2 months in patients with Grade 2b, with no significant difference. There was no clear difference in the incidence rate of ≥grade 3 adverse events between CP-A and CP-B. OS-r and OS-s were significantly correlated.Even patients with impaired liver function achieved the desired therapeutic effects by safely reducing the starting dose of regorafenib according to both impaired liver function and adverse events during pretreatment. Regorafenib may be considered to be an effective treatment after sorafenib monotherapy in patients with impaired liver function.

Phytochemical Information and Biological Activities of Quinolizidine Alkaloids in Sophora: A Comprehensive Review.

Quinolizidine alkaloids, a main form of alkaloids found in the genus Sophora, have been shown to have many pharmacological effects. This review aims to summarize the photochemical reports and biological activities of quinolizidine alkaloids in Sophora. The collected information suggested that a total of 99 quinolizidine alkaloids were isolated and detected from different parts of Sophora plants, represented by lupinine-type, cytisine-type, sparteine-type, and matrine-type. However, quality control needs to be monitored because it could provide basic information for the reasonable and efficient use of quinolizidine alkaloids as medicines and raw materials. The nonmedicinal parts may be promising to be used as a source of quinolizidine alkaloid raw materials and to reduce the waste of resources and environmental pollution. In addition, the diversity of chemical compounds based on the alkaloid scaffold to make a biological compound library needs to be extended, which may reduce toxicity and find new bioactivities of quinolizidine alkaloids. The bioactivities most reported are in the fields of antitumor activity along with the effects on the cardiovascular system. However, those studies rely on theoretical research, and novel drugs based on quinolizidine alkaloids are expected.

Evaluating the Strength of the Association Between Industry Payments and Prescribing Practices in Oncology.

BACKGROUND: Financial relationships between physicians and the pharmaceutical industry are common, but factors that may determine whether such relationships result in physician practice changes are unknown. MATERIALS AND METHODS: We evaluated physician use of orally administered cancer drugs for four cancers: prostate (abiraterone, enzalutamide), renal cell (axitinib, everolimus, pazopanib, sorafenib, sunitinib), lung (afatinib, erlotinib), and chronic myeloid leukemia (CML; dasatinib, imatinib, nilotinib). Separate physician cohorts were defined for each cancer type by prescribing history. The primary exposure was the number of calendar years during 2013-2015 in which a physician received payments from the manufacturer of one of the studied drugs; the outcome was relative prescribing of that drug in 2015, compared with the other drugs for that cancer. We evaluated whether practice setting at a National Cancer Institute (NCI)-designated Comprehensive Cancer Center, receipt of payments for purposes other than education or research (compensation payments), maximum annual dollar value received, and institutional conflict-of-interest policies were associated with the strength of the payment-prescribing association. We used modified Poisson regression to control confounding by other physician characteristics. RESULTS: Physicians who received payments for a drug in all 3 years had increased prescribing of that drug (compared with 0 years), for renal cell (relative risk [RR] 1.81, 95% confidence interval [CI] 1.58-2.07), CML (RR 1.22, 95% CI 1.08-1.39), and lung (RR 1.69, 95% CI 1.58-1.82), but not prostate (RR 0.97, 95% CI 0.93-1.02). Physicians who received compensation payments or >$100 annually had increased prescribing compared with those who did not, but NCI setting and institutional conflict-of-interest policies were not consistently associated with the direction of prescribing change. CONCLUSION: The association between industry payments and cancer drug prescribing was greatest among physicians who received payments consistently (within each calendar year). Receipt of payments for compensation purposes, such as for consulting or travel, and higher dollar value of payments were also associated with increased prescribing. IMPLICATIONS FOR PRACTICE: Financial payments from pharmaceutical companies are common among oncologists. It is known from prior work that oncologists tend to prescribe more of the drugs made by companies that have given them money. By combining records of industry gifts with prescribing records, this study identifies the consistency of payments over time, the dollar value of payments, and payments for compensation as factors that may strengthen the association between receiving payments and increased prescribing of that company's drug.

Approved Treatments for Patients with Recurrent High-grade Gliomas.

OBJECTIVES: To review the existing glioma literature and National Comprehensive Cancer Network current standard-of care guidelines for recurrent high-grade glioma, which includes surgery, radiation, and systemic therapies. DATA SOURCES: PubMed, MedlinePlus, Science Direct, National Comprehensive Cancer Network, and Google Scholar were searched. Key words for databases were high-grade glioma, glioblastoma, recurrent, surgery, radiation, and systemic therapy. CONCLUSION: Approved treatments for patients with recurrent high-grade glioma are limited and do not significantly impact progression-free survival rates, nor do they offer long-term benefit in symptom improvement or quality of life. Particular consideration for progression versus pseudoprogression should be evaluated before pursuing recurrent therapies. IMPLICATIONS FOR NURSING PRACTICE: Given the limited availability of standard-of-care treatments, clinical trials should be prioritized to maximize future treatment options. Individual performance status, genetic and molecular profiles, as well as goals of care and quality of life are important considerations in the context of treatment plans.

Validity and Reliability of Value Assessment Frameworks for New Cancer Drugs.

BACKGROUND: Several organizations have developed frameworks to systematically assess the value of new drugs. These organizations include the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the Institute for Clinical and Economic Review (ICER), and the National Comprehensive Cancer Network (NCCN). OBJECTIVES: To understand the extent to which these four tools can facilitate value-based treatment decisions in oncology. METHODS: In this pilot study, eight panelists conducted value assessments of five advanced lung cancer drugs using the ASCO, ESMO, and ICER frameworks. The panelists received instructions and published clinical data required to complete the assessments. Published NCCN framework scores were abstracted. The Kendall's W coefficient was used to measure convergent validity among the four frameworks. Intraclass correlation coefficients were used to measure inter-rater reliability among the ASCO, ESMO, and ICER frameworks. Sensitivity analyses were conducted. RESULTS: Drugs were ranked similarly by the four frameworks, with Kendall's W of 0.703 (P = 0.006) across all the four frameworks. Pairwise, Kendall's W was the highest for ESMO-ICER (W = 0.974; P = 0.007) and ASCO-NCCN (W = 0.944; P = 0.022) and the lowest for ICER-NCCN (W = 0.647; P = 0.315) and ESMO-NCCN (W = 0.611; P = 0.360). Intraclass correlation coefficients (confidence interval [CI]) for the ASCO, ESMO, and ICER frameworks were 0.786 (95% CI 0.517-0.970), 0.804 (95% CI 0.545-0.973), and 0.281 (95% CI 0.055-0.799), respectively. When scores were rescaled to 0 to 100, the ICER framework provided the narrowest band of scores. CONCLUSIONS: The ASCO, ESMO, ICER, and NCCN frameworks demonstrated convergent validity, despite differences in conceptual approaches used. The ASCO inter-rater reliability was high, although potentially at the cost of user burden. The ICER inter-rater reliability was poor, possibly because of its failure to distinguish differential value among the sample of drugs tested. Refinements of all frameworks should continue on the basis of further testing and stakeholder feedback.

[Oncology medications prescription in a cancer service: appropriateness to clinical practice guidelines]. / Prescripción de medicamentos oncológicos en un Servicio de Oncología: adecuación a las guías de práctica clínica.

OBJECTIVE: To assess prescription of oncology medications in municipal public health network of Rosario for its appropriateness to clinical practice guidelines. METHODS: Descriptive pharmacoepidemiological study in adult patients in an Oncology Service between January and June 2012. Compliance requirements with clinical practice guidelines were evaluated. RESULTS: 51.8% of diagnoses had at least one prescription medication that did not match recommendation by at least one of the guides considered. Prescriptions of doxorrubicine and ifosfamide did not agree with the recommendation of any reference guides. 5.4% of prescriptions weren´t considered by local guides, nor 7.7% by national on es. Regarding comparison with international guidelines: 4.2% of prescriptions weren ´t considered by the European Society for Medical Oncology guidelines, 2.3% not considered by the American Cancer Society and only 1.9% were not considered by the National Comprehensive Cancer Network ones. CONCLUSIONS: Prescription of oncology treatments is closer to international reference guides. One reason could be that there is still no standard definition in the management of tumor diseases by the National State.

Objetivo: Evaluar la prescripción de medicamentos oncológicos de la Red de Salud Pública Municipal de Rosario según su adecuación las guías de práctica clínica. Método: Estudio farmacoepidemiológico descriptivo en pacientes adultos en un Servicio Oncológico. Enero-junio 2012. Se evaluó la adecuación de las prescripciones a las guías de práctica clínica de referencia. Resultados: El 51,8 % de los diagnósticos tuvo al menos un medicamento prescripto que no coincidía con lo recomendado por al menos una de las guías consideradas. Las prescripciones de doxorrubicina e ifosfamida no coincidieron con lo recomendado por ninguna guía. El 5,4% de las prescripciones no estaban consideradas en las guías locales, el 7,7% no lo estaban en las nacionales y, respecto de las internacionales, el 4,2 % no estaban consideradas en la European Society for Medical Oncology, el 2,3% por el American Cancer Society y solo el 1,9% por la National Comprehensive Cancer Network. Conclusiones: La prescripción de oncológicos se adecúa más a las guías internacionales. Podría deberse a que no existe aún una definición estándar en el manejo de las patologías tumorales por parte del Estado Nacional.

SFPO and ESOP recommendations for the practical stability of anticancer drugs: an update.

The recommendations for the practical stability of anticancer drugs published in 2010 by the French Society of Hospital Pharmacists (SFPO) and the European Society of Oncology Pharmacists (ESOP) have been updated. Ten new molecules have been included (asparaginase, azacitidine, bevacizumab, clofarabine, eribuline mesylate, folinate sodium, levofolinate calcium, nelarabine, rituximab, temsirolimus).

Separation and determination of four ganoderic acids from dried fermentation mycelia powder of Ganoderma lucidum by capillary zone electrophoresis.

Ganoderic acids (GAs) were bioactive secondary metabolites produced by a traditional mushroom Ganoderma lucidum. We describe a simple and efficient method for the separation and quantitative determination of four GAs, namely Ganoderic acid T (GA-T), Ganoderic acid Mk (GA-Mk), Ganoderic acid Me (GA-Me) and Ganoderic acid S (GA-S) from dried triterpene-enriched extracts of G. lucidum mycelia powder by capillary zone electrophoresis (CZE). Under the optimum conditions, the four GAs reached the baseline separation in 9 min with Glycyrrhetinic acid (GTA) as internal standard. The four GAs and internal standard (GTA) were detected at a wavelength 245 nm. All calibration curves showed good linearity (r(2)>0.9958) within test ranges. Limit of detection (LOD) and limit of quantification (LOQ) were less than 0.6 and 1.8 microg/mL, respectively. The relative standard deviation (R.S.D.) values of precision and recoveries were less than 5% and recoveries ranged from 91.4% to 103.6%. This was the first report on simultaneous determination of the four GAs and the results provided a firm basis for the trace analysis of GAs in dried fermentation mycelia powder of G. lucidum with high accuracy.

Symptomatic comparison in efficacy on patients with benign prostatic hyperplasia treated with two therapeutic approaches.

OBJECTIVES: A randomised controlled trial was performed to compare the symptomatic effects on patients with benign prostatic hyperplasia (BPH) treated by two therapeutic approaches - the Western medicine (WM) and traditional Chinese medicine (TCM). METHODS: Four primary outcome measures, namely the quality of life (QOL), maximum urine flow ratio (UFR), International Prostate Symptom Score (IPSS) and prostate volumes, as well as four urethra-related and 35 non-urethra-related symptoms, were investigated to evaluate the effects on 31 BPH patients subjected to WM (Terazosin Hydrochloride Hytrin, THH) and 30 cases to TCM (herbal Saxifrage tablet, HST). The effects of both treatments are compared by the two-sample Kolmogorov-Smirnov test. The contributions of symptoms for four assessments are analysed by the logistic regression model and the Chow test. RESULTS: The effect of TCM is weaker than that of WM in the assessment of the IPSS score (p<0.05), and both treatments are similar in the prostate volumes, the maximum UFR and the QOL assessments (p>0.05), as well as in the effective number of urethra-related or non-urethra-related symptoms before and after treatment (p>0.05). By comparing the linear regression models, different urethra-related and non-urethra-related symptom patterns associated with TCM and WM therapies are detected for four assessments, especially for the prostate volume assessment (p<0.01). CONCLUSION: TCM (HST) is a potentially effective treatment in improving the QOL, prostate volumes and maximum UFR for patients with BPH, though it is less effective in ameliorating the IPSS score when compared with WM (THH). The non-urethra-related symptoms experienced by BPH patients might be one of the parameters to further achieve the tailored diagnosis and treatment for BPH.

[Chemical evaluation by cancer cell line panel and its role in molecular target-based anticancer drug screening].

Mechanism-based or target-based evaluation of chemicals is important in the discovery and development of anticancer drugs. A new scale for the mechanism-oriented evaluation is acquired by creating a database of drugs that includes their activities concerning growth inhibition against a set of cancer cell lines and by employing a specific data-mining method (Paull KD, et al: J Natl Cancer Inst 81: 1088-1092, 1989). According to this principle, we have established a new system for drug evaluation using a panel of 39 human cancer cell lines, JFCR-39 Cell Line Panel. The JFCR-39 Cell Line Panel is a system combining a wet system (drug-sensitivity test) and a dry system (data base and its mining), and can predict the mechanism of action of chemicals. Therefore, it is useful in anticancer drug discovery. The JFCR-39 Cell Line Panel now plays an important role as a core drug evaluation system in the molecular target-based drug screening conducted by Screening Committee of New Anticancer Agents supported by Grant-in-Aid for Scientific Research on Priority Area "Cancer" from The Ministry of Education, Culture, Sports, Science and Technology, Japan. I outlined the JFCR-39 Cell Line Panel in this review.

A method for biological control of a complex phytoadaptogen.

We propose a method for standardization of complex adaptogen-containing preparations. The method is based on acceleration of baking yeast strain growth on energy-depleted medium in the presence of the test agent. This method allows simple quantitative biological control of phytoadaptogens and comparison of adaptogenic activity of mono- and complex preparations.

Herbal cancer cures on the Web: noncompliance with The Dietary Supplement Health and Education Act.

BACKGROUND AND OBJECTIVES: A significant portion of the US population uses the Internet to obtain health information; nearly half of Internet users admit that this information influences decisions about their health care and medical treatments. Concurrently, approximately one third of the population uses herbal supplements; a higher percentage is noted for subgroups of cancer patients. The Dietary Supplement Health and Education Act (DSHEA) of 1994 contained regulatory standards for herbal supplements, including restricting any claims for disease prevention, treatment, or cure. This study determined the degree of compliance with the DSHEA, as applied to Internet sites focusing on the subject of herbal supplements and cancer. METHODS: Internet searches were conducted using six popular search engines and three master search engines in October-December 2000 using the linked terms herb and cancer. The Internet sites identified through this search process were examined for categories of information including claims regarding prevention, treatment, or cure; commercial nature; DSHEA and physician consultation warnings; country of origin; and use of research and testimonials. Additionally, commercial sites were reviewed to identify tactics used to promote products or services. RESULTS: Each of the six primary search engines provided between 11,730 and 58,605 matches for herb and cancer. Further cross matching with the three master search engines identified 70 non-repeating sites that appeared on all three master search engines. Of these 70 sites, nine were irrelevant matches or no longer functioning. Of the remaining 61, 34 (54%) were commercial sites (CS) and 27 (42.8%) were noncommercial sites (NCS). Of the CS surveyed, prevention, treatment, and cure were discussed 92%, 89%, and 58%, respectively. CS provided testimonials, physician consultation recommendations, and DSHEA warnings 89%, 38.8%, and 36.1% of the time, respectively. CS provided research with references 30.6% of the time versus 92.6% of the time in NCS. All international commercial sites surveyed claimed herbal cancer cures. CONCLUSIONS: Although the DSHEA was enacted and amended to decrease unlawful claims of disease prevention, treatment, and cure, the results of this study indicate that such claims are prevalent on commercial Internet sites. A majority of sites claim cancer cures through herbal supplementation with little regardfor current regulations, and such claims were more common on sites operated from outside the United States.

Tea and cancer prevention: an evaluation of the epidemiologic literature.

Animal and in vitro studies provide evidence of an anticarcinogenic potential of active ingredients in teas. This review encompasses epidemiologic studies of stomach, colon, and lung cancer as well as the evidence of a relationship between tea drinking and cancer at large in humans. Cohort studies do not suggest a protective role for tea drinking in the total risk of cancer. Site-specific studies reveal a more complex picture. The epidemiologic studies on tea drinking and stomach cancer do not justify claims of a cancer-protective effect. A protective effect of green tea on the development of colon cancer is suggested. The evidence regarding black tea is less clear, with some indication of a risk of colon or rectal cancer associated with regular use of black tea. The studies on tea and lung cancer also suggest an increased risk with increased tea consumption. The range and crude categorization of tea consumption, choice of control groups, and inadequate control for confounding might have obscured possible relationships. From the limited studies that suggest a favorable effect from tea, it is likely that benefits are restricted to high intakes in high-risk populations.

The evidence for soybean products as cancer preventive agents.

There is much evidence suggesting that compounds present in soybeans can prevent cancer in many different organ systems. The evidence for specific soybean-derived compounds having a suppressive effect on carcinogenesis in animal model systems is limited, however. There is evidence that the following isolated soybean derived products suppress carcinogenesis in vivo: a protease inhibitor, the Bowman-Birk inhibitor, inositol hexaphosphate (phytic acid) and the sterol beta-sitosterol. Other compounds that may be able to suppress carcinogenesis in animals are the soybean isoflavones. Soybean compounds reported to have other types of anticarcinogenic activity include soybean trypsin inhibitor, saponins and genistein. There is much evidence to suggest that diets containing large amounts of soybean products are associated with overall low cancer mortality rates, particularly for cancers of the colon, breast and prostate. It is believed that supplementation of human diets with certain soybean products shown to suppress carcinogenesis in animals could markedly reduce human cancer mortality rates.

Soybean phytoestrogen intake and cancer risk.

Because many Western diseases are hormone-dependent cancers, we have postulated that the Western diet, compared with a vegetarian or semi-vegetarian diet, may alter hormone production, metabolism or action at the cellular level. Recently, our interest has been focused on the cancer-protective role of some hormone-like diphenolic phytoestrogens of dietary origin, the lignans and isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids but also lignans), as well as whole grain cereals, seeds, probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds with weak estrogenic and antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation and angiogenesis, making them strong candidates for a role as natural cancer protective compounds. Epidemiological investigations support this hypothesis, because the highest levels of these compounds are found in countries or regions with low cancer incidence. This report is a review of results that suggest that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds.