Chemotherapy-induced Side Effects Research Articles

Zinc as a complementary treatment for cancer patients: a systematic review

Zinc is a trace element that plays an important role in the immune system and cell growth. The role of zinc in cancer treatment has been discussed for some time, however without reaching an evidenced-based consensus. Therefore, we aim to critically examine and review existing evidence on the role of zinc during cancer treatment. In January 2019, a systematic search was conducted searching five electronic databases (Embase, Cochrane, PsychINFO, CINAHL and PubMed) to find studies concerning the use, effectiveness and potential harm of zinc therapy on cancer patients. Out of initial 5244 search results, 19 publications concerning 23 studies with 1230 patients were included in this systematic review. The patients treated with zinc were mainly diagnosed with head and neck cancer and underwent chemo-, radio- or concurrent radio-chemotherapy. Interventions included the intake of different amounts of zinc supplements and oral zinc rinses. Outcomes (primary endpoints) investigated were mucositis, xerostomia, dysgeusia, pain, weight, dermatitis and oral intake of nutrients. Secondary endpoints were survival data, quality of life assessments and aspects of fatigue, immune responses and toxicities of zinc. The studies were of moderate quality reporting heterogeneous results. Studies have shown a positive impact on the mucositis after radiotherapy. No protection was seen against mucositis after chemotherapy. There was a trend to reduced loss of taste, less dry mouth and oral pain after zinc substitution. No impact was seen on weight, QoL measurements, fatigue, and survival. The risk of side effects from zinc appears to be relatively small. Zinc could be useful in the prevention of oral toxicities during irradiation. It does not help in chemotherapy-induced side effects.

Phytochemicals in Chemoprevention: A Cost-Effective Complementary Approach.

Cancer is one of the leading causes of death across the world. Although conventional cancer treatments such as chemotherapy and radiotherapy have effectively decreased cancer progression, they come with many dose-limiting side-effects. Phytochemicals that naturally occur in spices, fruits, vegetables, grains, legumes, and other common foods are surprisingly effective complements to conventional cancer treatments. These biologically active compounds demonstrate anticancer effects via cell signaling pathway interference in cancerous cells. In addition, phytochemicals protect non-cancerous cells from chemotherapy-induced side-effects. This paper addresses the not only the potential of phytochemicals quercetin, isoflavones, curcumin, catechins, and hesperidin in terms of cancer treatment and protection against side-effects of chemotherapy, but also methods for increasing phytochemical bioavailability.

The Effects of Curcumin on the Side Effects of Anticancer Drugs in Chemotherapy: A Randomized Controlled Trial.

Curcumin, the active ingredient of the spice turmeric, has been shown to have anticancer activities in several preclinical and clinical studies. The prophylactic effect of curcumin against chemotherapy-induced damage and side effects was evaluated in a double-blind, placebo-controlled randomized trial. Eighty cancer patients on standard chemotherapy regimens were randomly assigned to receive curcumin as adjuvant therapy (500 mg per 12hours) and matched control group to receive placebo for 9weeks. Pre- and post-intervention, the changes in the health-related quality-of-Life (QoL) score (based on the University of Washington Quality-of-Life (UW-QoL) questionnaire, version 3), clinical symptoms, and hematological and biochemical parameters were assessed. Comparison between groups based on total QoL score showed that curcumin supplementation was not associated with improved QoL (P=0.102). Hematological and biochemical analysis showed no statistical differences between the groups at the end of the trial (P>0.05). However, during the trial, significant differences were observed in hemoglobin (Hb), hematocrit (HCT), lactic acid dehydrogenase (LDH), serum glutamic-oxaloacetic transaminase (SGOT), and anaplastic lymphoma kinase (ALK) between the groups (P<0.05). Future studies in a larger homogenous population of cancer patients are required to confirm the adjuvant effect of curcumin on chemotherapy-induced QoL.

Prophylactic Acupuncture Treatment During Chemotherapy in Patients With Breast Cancer: Results of a Qualitative Study Nested in a Randomized Pragmatic Trial.

Background:In a randomized controlled trial, compared with standard care alone in breast cancer, acupuncture as a prophylactic treatment did not show better quality of life or fewer side effects of chemotherapy (NCT01727362 [clinicaltrials.gov]). The aim of the qualitative part of this mixed methods study was to better understand the subjective perspectives of the patients regarding quality of life during chemotherapy and the perceived effects of acupuncture.Methods:In a nested retrospective qualitative study, semi-structured telephone interviews were conducted with 5 responders and 5 non-responders (defined by the outcome of the primary parameter FACT-B) who were randomly selected from both study arms. The interviews were digitally recorded, pseudonymized, transcribed, and then deductively and inductively analyzed according to Qualitative Content Analysis using MAXQDA® software.Results:A total of 20 patients were included in the qualitative part of the study. In both groups, most women stated that their quality of life was surprisingly better than what they had expected before starting the chemotherapy. All patients of the acupuncture group experienced the acupuncture treatments as relaxing and beneficial, mentioning a friendly setting, and empathic attitude of the therapist. Most of these patients stated that the acupuncture treatment reduced chemotherapy-induced side effects. The patients reported that acupuncture was supportive for coping with the disease in a salutogenic way. For all patients, finding strategies to cope with life-threatening cancer and the side effects of chemotherapy was essential, for example, keeping a positive attitude toward life, selecting social contacts, and staying active as much as possible.Conclusions:Patients in the acupuncture group reported positive effects on psychological and physical well-being after receiving the study intervention. For all patients, having coping strategies for cancer seemed to be more important than reducing side effects. Therefore, further studies should focus more on coping strategies and reducing acute side effects.

Chinese Herbal Medicine for Reducing Chemotherapy-Associated Side-Effects in Breast Cancer Patients: A Systematic Review and Meta-Analysis

BackgroundChemotherapy usually induces a variety of side-effects in cancer treatment as it cannot tell normal cells apart from cancer cells and kills both. Chinese herbal medicine (CHM) has been regarded as a potential effective intervention for relieving the side-effects of chemotherapy in breast cancer patients.ObjectiveThis study aims to conduct a comprehensive systematic review and meta-analysis to evaluate the efficacy of CHM as adjuvant therapy for reducing the chemotherapy-induced side-effects in the treatment of breast cancer.MethodsMain electronic databases were searched up to May 2020 for Randomized Controlled Trials (RCTs) evaluating the effect of CHM on breast cancer patients with chemotherapy. The PRISMA statement was adopted in this study and meta-analyses were performed.ResultsThe included studies showed unsatisfied quality. Results based on available literature indicated that the adjunctive use of CHM with chemotherapy may reduce the chemotherapeutic agents-associated adverse events, including nausea and vomiting, diarrhea, alopecia, myelosuppression, and impaired immune function.ConclusionA confident conclusion could not be have due to the lack of large scale and high quality trials.

Voluntary wheel running ameliorates select paclitaxel chemotherapy-induced sickness behaviors and associated melanocortin signaling

While chemotherapy remains a common cancer treatment, it is associated with debilitating side effects (e.g., anorexia, weight loss, and fatigue) that adversely affect patient quality of life and increase mortality. However, the mechanisms underlying taxane chemotherapy-induced side effects, and effective treatments to ameliorate them, are not well-established. Here, we tested the longitudinal relationship between a clinically-relevant paclitaxel regimen, inflammation, and sickness behaviors (loss of body mass, anorexia, fever, and fatigue) in adult, female mice. Furthermore, we sought to identify the extent to which voluntary exercise (wheel running) attenuates paclitaxel-induced sickness behaviors and underlying central pathways. Body mass and food intake decreased following six doses of chemotherapy treatment relative to vehicle controls, lasting less than 5 days after the last dose. Paclitaxel treatment also transiently decreased locomotion (open field test), voluntary wheel running, home-cage locomotion, and core body temperature without affecting motor coordination (rotarod task). Circulating interleukin (IL)-6 and hypothalamic Il1b gene expression remained elevated in chemotherapy-treated mice at least 3 days after the last dose. Exercise intervention did not ameliorate fatigue or inflammation, but hastened recovery from paclitaxel-induced weight loss. Body mass recovery was associated with the wheel running-induced recovery of body composition, paclitaxel-induced alterations to hypothalamic melanocortin signaling, and associated peripheral circulating hormones (ghrelin and leptin). The present findings demonstrate the benefits of exercise on faster recovery from paclitaxel-induced body mass loss and deficits in melanocortin signaling and suggests the development of therapies targeting the melanocortin pathway to reduce paclitaxel-induced weight loss.

Dermatologic sequelae of breast cancer: From disease, surgery, and radiation

The care of breast cancer patients is important to dermatologists. Breast cancer's initial presentation, clinical progression, and its associated treatments can result in a variety of cutaneous complications. Dermatologists may be the first to identify a breast cancer diagnosis, as a subset of patients first present with direct extension of an underlying tumor or with a cutaneous metastasis. The surgical treatment of breast cancer also begets a variety of skin sequelae, including postoperative lymphedema, soft tissue infections, seromas, pyoderma gangrenosum, and scarring disorders. Moreover, breast cancer radiation treatment commonly results in skin changes, which can range from mild and temporary dermatoses to chronic and disfiguring skin ulceration, fibrosis, and necrosis. Radiation may also precipitate secondary malignancies, such as angiosarcoma, as well as rarer dermatologic diseases, such as radiation-induced morphea, lichen planus, and postirradiation pseudosclerodermatous panniculitis. Finally, breast cancer is also associated with an array of paraneoplastic phenomena, including Sweet's syndrome and the rarer intralymphatic histiocytosis. Herein, we review the dermatological manifestations of breast cancer, including conditions associated with its presentation, progression, and treatment sequelae. Chemotherapy-induced cutaneous side effects are beyond the scope of this review. This article provides a comprehensive review for dermatologist to be able to identify, diagnose, and manage breast cancer patients from initial presentation to treatment monitoring and subsequent follow-up.

GDF-15 Neutralization Alleviates Platinum-Based Chemotherapy-Induced Emesis, Anorexia, and Weight Loss in Mice and Nonhuman Primates

Platinum-based cancer therapy is restricted by dose-limiting side effects and is associated with elevation of growth differentiation factor 15 (GDF-15). But whether this elevation contributes to such side effects has been unclear. Here, we explored the effects of GDF-15 blockade on platinum-based chemotherapy-induced emesis, anorexia, and weight loss in mice and/or nonhuman primate models. We found that circulating GDF-15 is higher in subjects with cancer receiving platinum-based chemotherapy and is positively associated with weight loss in colorectal cancer (NCT00609622). Further, chemotherapy agents associated with high clinical emetic score induce circulating GDF-15 and weight loss in mice. Platinum-based treatment-induced anorexia and weight loss are attenuated in GDF-15 knockout mice, while GDF-15 neutralization with the monoclonal antibody mAB1 improves survival. In nonhuman primates, mAB1 treatment attenuates anorexia and emesis. These results suggest that GDF-15 neutralization is a potential therapeutic approach to alleviate chemotherapy-induced side effects and improve the quality of life.

Phospho-Proteomic Profiling of T-Cell Acute Lymphoblastic Leukemia Identifies Targetable Kinase Activities and Novel Treatment Combination Strategies

Introduction Intensive multi-agent treatment has boosted survival up to 80% of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients. Nevertheless, relapsed patients have a poor prognosis due to acquired therapy resistance while most survivors have detrimental chemotherapy-induced side effects. Therefore, novel targeted therapies are urgently needed since further intensification of the current standard treatment regimen is not feasible for refractory/relapsed cases. Protein kinase inhibitors (PKIs) are amongst the most successful cancer treatments. Targetable kinases activated by gene fusions are rare in T-ALL and include subclonal NUP214-ABL1 fusion in 6% of cases or other rare clonal ABL1 fusions. Nevertheless, leukemic blasts rely on enhanced kinase signaling to sustain their dysregulated proliferation. Protein kinases can be hyper-activated even in the absence of defects in their genes. Thus, together with the identification of genomic aberrations, phospho-proteomics can provide information on pathway activation, signaling networks and aberrant kinase activities that offer important opportunities for targeted therapies. Aim Here, we aimed to identify and quantify kinase activation in T-ALL cell lines that may yield differential sensitivity to PKIs in vitro. This approach could pinpoint targetable leukemia vulnerabilities and provide effective (combination) treatment strategies. Methods Protein extracts from 11 T-ALL cell lines were enriched for phospho-peptides by titanium dioxide enrichment and anti-phospho tyrosine immunoprecipitation followed by liquid chromatography - tandem mass spectrometry (MS). Subsequently, the Integrative Inferred Kinase Activity (INKA) pipeline was used to rank activated kinases in our panel (Beekhof et al., 2019). Based on these data, selected kinase inhibitors were tested in vitro as single treatment or in combinations. Eventually, drugs of interest were further tested ex vivo in a cohort of T-ALL patient-derived xenografts (PDXs). Results MS-based phospho-proteome profiling of 11 T-ALL cell lines identified about 3700 tyrosine phospho-sites and more than 13300 serine/threonine phosphorylation sites. We found SRC-family kinases including LCK, SRC, FYN, and YES1 as most activated kinases in many T-ALL cell lines while ABL1, ZAP70, LYN, and FGR were detected only in specific lines. Additionally, other kinases including CDK1/2 and PAK1/2 were found to be activated in all the cell lines while activation of the INSR/IGF-1R axis was detected only in a subset of lines. We then tested cellular response to multiple clinically relevant PKIs based on predicted kinase activities. The in vitro drug screening showed an effective response and G1-arrest following treatment with the CDK1/2 inhibitor milciclib in all the cell lines tested, with IC50 values between 10nM and 1uM. Despite a general SRC-family kinases activation profile, dual SRC/ABL inhibitors like dasatinib reduced cellular viability only in cell lines with ABL1 fusions or LCK translocations (IC50 &amp;lt; 10nM) while other lines lacking ABL or LCK rearrangements were affected at much higher drug concentration (IC50 &amp;gt; 3uM, which is beyond the clinical achievable plasma concentration). Thus, PKIs were tested in combination with other relevant inhibitors based on additional kinase activities detected. Interestingly, the concomitant inhibition of the SRC-family kinases by dasatinib and the INSR/IGF-1R axis by BMS-754807 led to a drastic reduction of cell viability at nanomolar concentrations even in cell lines that did not respond to dasatinib, identifying a novel possible effective combination strategy for T-ALL. Eventually, we tested clinically relevant PKIs in 50 PDXs ex vivo and identified various T-ALL samples with a high sensitivity to dasatinib single treatment (IC50 &amp;lt; 100nM) as previously reported by others (Frismantas et al., 2017). Moreover, 70% of our PDXs efficiently responded to the broad spectrum kinase inhibitor midostaurin (IC50 &amp;lt; 1uM), highlighting the importance of targeting multiple signaling nodes simultaneously to tackle T-ALL vulnerabilities. Conclusions Ranking kinase activities and signaling networks from phospho-proteomic data can guide the use of PKIs as treatment option for T-ALL patients. Moreover, kinase activity profiling can provide insights for efficient treatment combination strategies to develop personalized medicine. Disclosures No relevant conflicts of interest to declare.

Abstract PO-047: Anti-proliferative effect of cannabidiol (CBD) against B and T-cell lymphoma

Abstract In the last two decades, Cannabinoids have been studied extensively for its potential use in various fields of medicine including oncology. Today some of the cannabinoids are FDA approved for the treatment of chemotherapy-induced side effects in cancer treatment however, studies are showing their effect against tumor growth as well. Aggressive B cell lymphoma or Non-Hodgkin lymphoma (NHL) is the fifth leading cause of human cancer death and is the second fastest-growing cancer with regard to mortality in people as 30% of patients develop resistance against chemotherapy. For this reason, it is essential to develop novel strategies to improve the outcome of patients suffering from aggressive or therapy-resistant lymphoma. The purpose of this study was to demonstrate the antitumor effects of cannabinoids in B cell lymphoma using canine as a model due to striking similarities b/w canine and human B cell lymphoma in histology, biology and gene expression. For this study, Canine B cell lymphoma cell lines 1771 and CLBL1 were cultured in RPMI. Expression of cannabinoid receptors studied using qPCR. Based on receptor expression cells were treated with receptor agonists (AEA, 2AG, CBD, THC, WIN and HU-210,) and antagonists (S16 and S28). Cell viability assessed using MTT assay. Biochemical analysis performed using spectrofluorometry to evaluate apoptotic makers involved in inducing cell death. Data was analyzed using ordinary one way ANOVA on Prism software. All B cell lymphoma cell lines showed positive expression of CB1 and CB2 receptors. Cell viability assay demonstrated a dose-dependent decrease in cell proliferation with all cannabinoid receptor agonists used except for 2AG. Biochemical analysis showed a decrease in nitrite and caspase activity in treated cells as compared to control untreated cells. Our results suggest that cannabinoids have an anti-proliferative and apoptotic effect on canine lymphoma cells and it can be developed as a potential anti-cancer agent for the treatment of canine and human B cell lymphoma. Citation Format: Saba Omer, Dawn Boothe, Mohammed Mansour, Muralikrishnan Dhanasekaran, Satyanarayana Pondugula. Anti-proliferative effect of cannabidiol (CBD) against B and T-cell lymphoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-047.

Sildenafil Potentiates the Therapeutic Efficacy of Docetaxel in Advanced Prostate Cancer by Stimulating NO-cGMP Signaling.

Docetaxel plays an indispensable role in the management of advanced prostate cancer. However, more than half of patients do not respond to docetaxel, and those good responders frequently experience significant cumulative toxicity, which limits its dose duration and intensity. Hence, a second agent that could increase the initial efficacy of docetaxel and maintain tolerability at biologically effective doses may improve outcomes for patients. We determined phosphodiesterase 5 (PDE5) expression levels in human and genetically engineered mouse (GEM) prostate tissues and tumor-derived cell lines. Furthermore, we investigated the therapeutic benefits and underlying mechanism of PDE5 inhibitor sildenafil in combination with docetaxel using in vitro, Pten conditional knockout (cKO), derived tumoroid and xenograft prostate cancer models. PDE5 expression was higher in both human and mouse prostate tumors and cancer cell lines compared with normal tissues/cells. In GEM prostate-derived cell lines, PDE5 expression increased from normal prostate (wild-type) epithelial cells to androgen-dependent and castrated prostate-derived cell lines. The addition of physiologically achievable concentrations of sildenafil enhanced docetaxel-induced prostate cancer cell growth inhibition and apoptosis in vitro, reduced murine 3D tumoroid growth, and in vivo tumorigenicity as compared with docetaxel alone. Furthermore, sildenafil enhanced docetaxel-induced NO and cGMP levels thereby augmenting antitumor activity. Our results demonstrate that sildenafil's addition could sensitize docetaxel chemotherapy in prostate cancer cells at much lesser concentration than needed for inducing cell death. Thus, the combinatorial treatment of sildenafil and docetaxel may improve anticancer efficacy and reduce chemotherapy-induced side-effects among patients with advanced prostate cancer.

Short-term fasting accompanying chemotherapy as a supportive therapy in gynecological cancer: protocol for a multicenter randomized controlled clinical trial

Background/objectivesA few preliminary studies have documented the safety and feasibility of repeated short-term fasting in patients undergoing chemotherapy. However, there is a lack of data from larger randomized trials on the effects of short-term fasting on quality of life, reduction of side effects during chemotherapy, and a possible reduction of tumor progression. Moreover, no data is available on the effectiveness of fasting approaches compared to so-called healthy diets. We aim to investigate whether the potentially beneficial effects of short-term fasting can be confirmed in a larger randomized trial and can compare favorably to a plant-based wholefood diet.MethodsThis is a multicenter, randomized, controlled, two-armed interventional study with a parallel group assignment. One hundred fifty patients, including 120 breast cancer patients and 30 patients with ovarian cancer, are to be randomized to one of two nutritional interventions accompanying chemotherapy: (1) repeated short-term fasting with a maximum energy supply of 350–400 kcal on fasting days or (2) repeated short-term normocaloric plant-based diet with restriction of refined carbohydrates. The primary outcome is disease-related quality of life, as assessed by the functional assessment of the chronic illness therapy measurement system. Secondary outcomes include changes in the Hospital Anxiety and Depression Score and as well as frequency and severity of chemotherapy-induced side effects based on the Common Terminology Criteria of Adverse Events. Explorative analysis in a subpopulation will compare histological complete remissions in patients with neoadjuvant treatments.Discussion/planned outcomesPreclinical data and a small number of clinical studies suggest that repeated short-term fasting may reduce the side effects of chemotherapy, enhance quality of life, and eventually slow down tumor progression. Experimental research suggests that the effects of fasting may partly be caused by the restriction of animal protein and refined carbohydrates. This study is the first confirmatory, randomized controlled, clinical study, comparing the effects of short-term fasting to a short-term, plant-based, low-sugar diet during chemotherapy on quality of life and histological tumor remission.Trial registrationClinicalTrials.gov NCT03162289. Registered on 22 May 2017

Prevalence and management of constipation in pediatric acute lymphoblastic leukemia in U.S. children's hospitals.

Children with acute lymphoblastic leukemia (ALL) suffer from a litany of chemotherapy-induced side effects. Constipation secondary to vinca alkaloids, environmental changes, and opioid use is a common issue for children newly diagnosed with leukemia. We analyzed data from 48 children's hospitals in the Pediatric Health Information System, extracting patients 1-21 years of age with ALL hospitalized from October 2015 through September 2019. Our objective was to investigate the prevalence, risk factors, and treatment of constipation in hospitalized children with ALL. We identified 4647 unique patients with an ALL induction admission. Constipation was the most common gastrointestinal diagnosis with 1576 (33.9%; 95% confidence interval [CI]: 32.6%-35.3%) patients diagnosed during induction admission and 19.8% in post-induction admissions. The most commonly administered constipation medications were poly-ethyl glycol (n=3385, 89.6%), followed by senna (n=1240, 32.8%), lactulose (n=916, 24.2%), and docusate (n=914, 24.2%). Multivariate logistic regression revealed the following variables to be significantly associated with the presence of a constipation diagnosis: age<6 years at induction (compared with those ≥12 years; odds ratios [OR]=1.32 [95% CI: 1.13-1.55]; P=<0.001), female sex (OR=1.16 [95% CI: 1.02-1.31]; P=0.024), increased length of hospitalization (OR=1.03 [95% CI: 1.02-1.04]; P<0.0001), use of non-fentanyl opioids for one or two days (OR=1.28 [95% CI: 0.99-1.65]; P=0.056), and use of non-fentanyl opioids>2 days (OR=1.53 [95% CI: 1.19-1.95]; P<0.001). A large portion of hospitalized children with ALL experience constipation and required medications. Increased attention should be paid to constipation prophylaxis and treatment in ALL patients, particularly at the start of induction therapy.

The efficacy and safety of moxibustion for chemotherapy-induced gastrointestinal adverse reaction: A protocol for systematic review and meta-analysis.

Background:Many cancer patients experience gastrointestinal adverse reaction during chemotherapy. Pharmacological interventions are commonly used to treat chemotherapy-induced gastrointestinal side effects but have various limitations. Clinical trials have indicated that moxibustion may alleviate gastrointestinal dysfunction and improve quality of life (QoL) after chemotherapy. This study aims to assess the efficacy and safety of moxibustion for chemotherapy-induced gastrointestinal adverse reaction through a systematic review and meta-analysis.Methods:All randomized controlled trials (RCTs) related to moxibution targeting chemotherapy-induced gastrointestinal adverse reaction will be searched in online databases, such as PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP Database) and WanFang Database from their inception to May 1, 2020. The primary outcome is the incidence and severity of chemotherapy-related gastrointestinal toxicities (nausea and vomiting, diarrhea and constipation). The secondary outcomes include the quality of life, biological parameters’ alteration, and adverse events. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 researchers. The Cochrane Collaboration's Review Manager (RevMan 5.3) software will be used to conduct the direct meta-analysis.Results:This study will provide a comprehensive review of the available evidence for the treatment of chemotherapy-induced gastrointestinal adverse reaction with moxibustion.Conclusion:The conclusion of this study will provide evidence to judge whether moxibustion is an effective and safety therapeutic intervention for chemotherapy-induced gastrointestinal adverse reaction.PROSPERO registration number:CRD42020182990.

Assessment of Norwegian physicians’ knowledge, experience and attitudes towards medical cannabis

Background Medicinal cannabis (MC) has been used extensively throughout history. However, its criminalization in the United States in 1937 spurred the international community to follow suit, including Norway. Despite being reintroduced as a medical treatment in many countries in recent years, the use of MC in Norway is confined to a select few patient groups, and medical specialists must formally apply for authorization from the Norwegian authorities to prescribe the drug. Objective To assess Norwegian physicians’ perceived knowledge of, experience with, and attitudes towards MC. Methods A cross-sectional survey consisting of 31 closed-ended items captured physicians’ perceived knowledge of, experience with, and attitudes towards this treatment. Results A total of 102 physicians participated in this study. Physicians generally agreed that MC is a legitimate treatment option (n = 45, 44.1%), that it represents a therapeutic agent for treating cancer and chemotherapy-induced side effects (n = 88, 86%), and that it has the potential to reduce unnecessary opioid use in patients with chronic pain (n = 40, 39.2%). Statistically significant differences were found between subgroups in the sample in terms of years of practice, specialty, age, country the medical diploma was obtained from, and practice type. Conclusions This study found acceptance of cannabis as a therapeutic agent as well as acceptance towards MC being introduced by prescription in Norway. Further large-scale in-depth studies on provider perspectives towards MC are warranted.

Evaluation of adverse effects of chemotherapy regimens of 5-fluoropyrimidines derivatives and their association with DPYD polymorphisms in colorectal cancer patients

Background5-Fluorouracil (5-FU) and capecitabine are fluoropyrimidine derivatives that mainly metabolized with dihydropyrimidine dehydrogenase enzyme (DPD). The genetic polymorphism in the genes encoding this enzyme may result in a decrease or loss of enzyme activity which may lead to the accumulation of medicines, their metabolites and potential toxicity.MethodThis cross-sectional study was conducted on 88 participants with colorectal cancer (CRC). After DNA extraction, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the DPD gene (DPYD) polymorphisms including IVS 14 + 1 G > A, 2846 A > T and 2194 G > A. Chemotherapy-induced side effects were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0).ResultData were collected from 227 chemotherapy cycles of 88 patients with CRC. In a comparison of FOLFOX and FOLFIRI regimens, there was no significant difference in the occurrence of chemotherapy-induced diarrhea, nausea, vomiting and oral mucositis. However, the peripheral neuropathy was more frequent in patients who were treated with FOLFOX (P < 0.001) and hair loss was more common in patients who received FOLFIRI regimen (P = 0.048).Incidence of the DPD IVS14 + 1 G > A polymorphism was observed in four patients (5.5%). There was no association between IVS14 + 1 G > A polymorphism and the occurrence of adverse reactions.ConclusionFOLFOX and FOLFIRI were the most common regimens in CRC patients and their toxicity profile was different in some adverse reactions. Prevalence of IVS14 + 1G > A variant was relatively higher than other similar studies.Trial registrationApproval code; IR.MAZUMS.REC.95.2480.

ZeOxaNMulti Trial: A Randomized, Double-Blinded, Placebo-Controlled Trial of Oral PMA-zeolite to prevent Chemotherapy-Induced Side Effects, in particular, Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most frequently reported adverse effect of oxaliplatin. In this study, we set out to evaluate the role of the panaceo-micro-activation (PMA) zeolite in the reduction of the incidence of CIPN and hematological and liver toxicity. The possible impact of the PMA-zeolite as an adjuvant therapeutic agent is based on its detoxification properties toward agents promoting the development of neuropathy (e.g., ammonium—recognized as a neurotoxic agent produced by tumors), as well as its positive impact on immunity and oxidative stress through its effects in the gastrointestinal tract. From April 2015 to October 2018, a total of 120 patients (pts) diagnosed with predominantly colorectal cancer requiring oxaliplatin-based chemotherapy were randomized to receive either the PMA-zeolite (Multizeo Med) or placebo while undergoing oxaliplatin-based chemotherapy. A nerve-conduction study (NCS) was planned at the baseline, after three and six months of chemotherapy, to evaluate CIPN. Furthermore, the evaluation of hematological and liver toxicity was performed during every cycle of chemotherapy. 70.6% and 64.3% of patients developed CIPN in the placebo and the PMA-zeolite group, respectively. Patients treated with the PMA-zeolite were able to undergo more cycles of chemotherapy (p = 0.03), which also indicates a significant improvement in tolerance to the therapy. The group treated with the PMA-zeolite showed a lower CIPN (although not statistically significant within the whole group of subjects) compared to patients receiving placebo. This advantage was, however, statistically significant in men (p = 0.047). In addition, supplementation with the PMA-zeolite resulted in a lower incidence of severe-grade hematological toxicity (trend toward statistical significance of p = 0.09 was observed). Cancer patients may benefit from the therapy with the appropriate certified zeolite-products (e.g., the PMA-zeolite) for human use in CIPN. The lower CIPN (statistically significant results in the male subgroup) was accompanied by a trend of lower incidence of severe-grade hematological toxicity. Furthermore, these benefits led to a better tolerance toward chemotherapy (increase in cycles) and allow an improved compliance with the oncological treatment protocol.

Cetuximab Maintenance Therapy in Patients with Unresectable Wild-Type RAS and BRAF Metastatic Colorectal Cancer: A Single-Institute Prospective Study.

Cetuximab plus FOLFIRI (leucovorin, fluorouracil, and irinotecan) is the preferred first-line therapy for RAS and BRAF wild-type (RBWT) metastatic colorectal cancer (mCRC). To counter chemotherapy-induced side effects, use of maintenance therapy is suggested. Therefore, we evaluated the efficacy and safety of cetuximab maintenance therapy in patients after effective completion of first-line induction therapy. This prospective study enrolled untreated patients with mCRC RBWT who received first-line cetuximab plus FOLFIRI therapy. Following this, patients with treatment response either entered observation (stop treatment) or maintenance treatment1 (cetuximab plus irinotecan) groups. After 6-12 cycles of maintenance treatment1, patients entered maintenance treatment2 (cetuximab only). If a patient progressed on maintenance 2, cetuximab plus FOLFIRI was reintroduced. The primary end point was failure-free survival (FFS), whereas the secondary end points included disease control rate (DCR), objective remission rate (ORR), and progression-free survival (PFS). Safety events were also evaluated. Among 79 enrolled patients, 72 completed first-line treatment effectively (DCR 91.1%, ORR 63.9%) and 44 entered maintenance1 [median PFS 1 (mPFS, maintenance1) 6.1months, 95% confidence interval (CI) 6.0-6.2; DCR 56.8%; ORR 22.7%]. Of them, 21 entered maintenance treatment2 (mPFS2 8.7months, 95% CI 3.3-14.1; DCR 28.6%; ORR 4.8%). Median FFS (mFFS) was significantly longer in the maintenance1 group compared with the observation group [12.7 vs. 3.0months; hazard ratio (HR) 0.202, 95% CI 0.111-0.369; P < 0.001]. Overall, mFFS was 19.0 and 9.3months in maintenance and observation groups, respectively (HR 0.211, 95% CI 0.117-0.380; P < 0.001). Rash acneiform, mucositis, and asthenia were commonly observed adverse events during maintenance treatment. Maintenance treatment with cetuximab after first-line therapy significantly improved FFS, with an acceptable safety profile in untreated patients with mCRC RBWT. Retrospectively registered, 2019/10/02, Chinese Clinical Trial Registry, ChiCTR number 1900026360.

Nephroprotection and chemotherapy sensitivity impact of metformin during cisplatin therapy; an updated review

Chemotherapy has been accepted as the most common choice for cancer treatment. However, chemotherapy-induced toxicity and chemotherapy resistance are the two challenging barriers to the treatment. Metformin is a safe, inexpensive, and the first line drug to treat type II diabetes. It has also a significant anti-tumor effect with a selective cytotoxic efficacy on cancer stem cells. It also has renoprotective efficacy. The current study contributes to incorporating metformin to chemotherapeutic agents to develop treatment efficiency and reduce the chemotherapy-induced side-effects (such as toxicity and resistance) and also to benefit the nephroprotective impact of this drug.

CN99 - Scalp cooler is effective in reducing chemotherapy-induced alopecia among breast cancer patients: A single institution experience

BackgroundChemotherapy-induced temporary hair loss is one of the most common and distressing side-effects of cancer therapy. Scalp cooling is a long known method to reduce chemotherapy-induced alopecia in cancer patients, especially when antracycline or taxanes are used. However scalp cooling to reduce hair loss is still a controversial issue. MethodsWe included 210 breast cancer patients receiving chemotherapy both in (neo) adjuvant and palliative setting. Evaluation was focused on the quantification of chemotherapy-induced alopecia (CIA), satisfaction and side effects of the scalp cooling system. the severity of hair loss was assessed according to CTCAE version 4.0 by the nurses team together with the patient. Nurses completed questionnaires on patients baseline characteristics and type of chemotherapy received during each session of scalp-cooling The following chemotherapeutic treatments were included: doxorubicin alone or in combination with cyclophosphamide (AC); AC followed by paclitaxel,paclitaxel alone; FEC ; FEC followed by docetaxel. ResultsThe mean overall success rate of scalp cooling (<50% hair loss) was at 62%. In the final results, major hair loss was avoided in 85% patients given taxane treatment, in 79% of patients given FEC treatment and in 32% of patients given AC treatment. None of these patients needed to use a wig and all of them were satisfied about the results at the final evaluation. 87% of the patients considered the avoidance of hair loss to be important before starting the chemotherapy. 12 patients discontinued scalp cooling for side-effects or low compliance. ConclusionsNurse team were properly trained and provided with higher experience; a standardized approach was used by the nurse staff for each patient with dedicated time. Our experience showed that scalp cooler provides a good chance for breast cancer patients to keep their hair during anthracyclines and/or taxane containing (neo-)adjuvant chemotherapy and could be integrated into daily practice of chemotherapy unit. Legal entity responsible for the studyFabrizio Artioli. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.