Common Adverse Effect Of Chemotherapy Research Articles

Electrical acupoint stimulation for the treatment of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis

BackgroundChemotherapy-induced nausea and vomiting (CINV) is the most common adverse effect of chemotherapy and affects the continuation of chemotherapy in cancer patients. Electrical acupoint stimulation (EAS), which includes electroacupuncture and transcutaneous electrical stimulation (TES), has been used to treat CINV. This meta-analysis aimed to evaluate the efficacy of EAS in the treatment of CINV. MethodsRandomized controlled trials (RCTs) of EAS for CINV retrieved form five key databases. Two researchers independently performed article screening, data extraction and data integration. The Cochrane Collaboration's tool for assessing risk of bias was used to assesse the methodological quality according to Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.4 was used to perform analyses. Results10 RCTs with a total of 950 participants were included. The results showed that there was no significant difference between EAS compared to sham EAS in terms of increasing the rate of complete control of CINV and decreasing the overall incidence of CINV [RR = 1.26, 95 % CI (0.96, 1.66), P = 0.95; RR = 1.16, 95 % CI (0.97, 1.40), p = 0.71]. In terms of CINV severity, EAS reduced the occurrence of moderate-to-severe CINV [RR = 0.60, 95 % CI (0.38, 0.94), P = 0.03; RR = 0.50, 95 % CI (0.33, 0.76), P = 0.001]. ConclusionEAS could improve moderate-to-severe CINV. However, EAS did not show a significant difference in reducing overall incidence and improving complete control rates compared with sham EAS. Due to limitations in the quality of the included articles, the available studies are insufficient to have sufficient evidence to confirm the efficacy of EAS for CINV. Validation with rigorously designed, large-sample, high-quality clinical trial studies may also be needed.

An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota.

Intestinal mucositis (IM) is a common adverse effect of chemotherapy, limiting its clinical application. Codonopsis pilosula-derived CP-A (an inulin-type fructan) is an edible Chinese medicine with anti-inflammatory and gastrointestinal protective effects, which may be useful for treating IM. Here, we explored CP-A's role in ameliorating IM induced by 5-fluorouracil (5-FU) and investigated the underlying mechanism using in vitro experiments and rat models. Western blotting, immunohistochemistry (IHC), and real-time PCR (RT-PCR) analyses were used to assess protein expression related to the extracellular-regulated protein kinases (ERK)/myosin light chain kinase (MLCK)/myosin light chain 2 (MLC2) signaling pathway and tight junction proteins. Inflammatory factors were quantified using enzyme-linked immunosorbent assays (ELISAs), and 16S rRNA amplicon sequencing was employed for cecum content analysis. The results indicated that CP-A restored body weight and food intake and reversed histopathological changes in IM rats. Further, abnormal MLCK activation induced by 5-FU was attenuated by CP-A via the ERK/MLCK/MLC2 pathway. CP-A treatment improved tight junction protein levels and reduced inflammatory factor expression. Moreover, CP-A intervention regulated the intestinal microbiota community structure, increasing the abundance of Lactobacillus and decreasing the abundance of Shigella. In conclusion, CP-A mitigates 5-FU-induced IM by inhibiting the ERK/MLCK/MLC2 pathway, reducing the expression of inflammatory factors, improving the intestinal mucosal barrier, and regulating the intestinal microbial community. This study highlights CP-A's therapeutic potential in IM treatment and provides insights for future research.

Oral mirtazapine decreases the gastrointestinal adverse effects in cats on doxorubicin chemotherapy

Anorexia, depression, and vomiting are the common adverse effects of chemotherapy in humans and animals. Mirtazapine is primarily used as an appetite stimulant and antiemetic in dogs and cats. Therefore, we evaluated the efficacy of mirtazapine in reducing the gastrointestinal adverse effects in cats receiving doxorubicin chemotherapy. This single-masked, placebo-controlled crossover study enrolled 11 cats with malignant mammary gland tumors. The cats were randomly assigned to receive either mirtazapine (1.88 mg/cat) or placebo every 48 h for 2 weeks from the first initiation of doxorubicin chemotherapy. Each cat was then crossed over to the alternate group on the subsequent chemotherapy with a 1-week wash-out period. The owners were asked to record appetite score, activity score, episodes of vomiting and diarrhea for 2 weeks after each doxorubicin administration. Cats treated with mirtazapine showed significantly increased bodyweight compared with those on placebo (P = 0.010). The appetite and activity scores during mirtazapine treatment was significantly higher than those during placebo treatment (P = 0.005 and 0.018, respectively). Furthermore, the prevalence of episodes of vomiting during mirtazapine treatment was significantly lower than that during placebo treatment (P = 0.026). Our results demonstrate that mirtazapine can significantly increase bodyweight, appetite, and activity and reduce vomiting in cats after doxorubicin chemotherapy.

Association between genetic variants of membrane transporters and the risk of high-grade hematologic adverse events in a cohort of Mexican children with B-cell acute lymphoblastic leukemia.

Advances in the understanding of the pathobiology of childhood B-cell acute lymphoblastic leukemia (B-ALL) have led towards risk-oriented treatment regimens and markedly improved survival rates. However, treatment-related toxicities remain a major cause of mortality in developing countries. One of the most common adverse effects of chemotherapy in B-ALL is the hematologic toxicity, which may be related to genetic variants in membrane transporters that are critical for drug absorption, distribution, and elimination. In this study we detected genetic variants present in a selected group genes of the ABC and SLC families that are associated with the risk of high-grade hematologic adverse events due to chemotherapy treatment in a group of Mexican children with B-ALL. Next generation sequencing (NGS) was used to screen six genes of the ABC and seven genes of the SLC transporter families, in a cohort of 96 children with B-ALL. The grade of hematologic toxicity was classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, Subsequently, two groups of patients were formed: the null/low-grade (grades 1 and 2) and the high-grade (grades 3 to 5) adverse events groups. To determine whether there is an association between the genetic variants and high-grade hematologic adverse events, logistic regression analyses were performed using co-dominant, dominant, recessive, overdominant and log-additive inheritance models. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated. We found two types of associations among the genetic variants identified as possible predictor factors of hematologic toxicity. One group of variants associated with high-grade toxicity risk: ABCC1 rs129081; ABCC4 rs227409; ABCC5 rs939338, rs1132776, rs3749442, rs4148575, rs4148579 and rs4148580; and another group of protective variants that includes ABCC1 rs212087 and rs212090; SLC22A6 rs4149170, rs4149171 and rs955434. There are genetic variants in the SLC and ABC transporter families present in Mexican children with B-ALL that can be considered as potential risk markers for hematologic toxicity secondary to chemotherapeutic treatment, as well as other protective variants that may be useful in addition to conventional risk stratification for therapeutic decision making in these highly vulnerable patients.

Novel targeted delivery of quercetin for human hepatocellular carcinoma using starch/polyvinyl alcohol nanocarriers based hydrogel containing Fe2O3 nanoparticles

The common adverse effects of chemotherapy are the reason for the use of effective, natural drugs and targeted administration to specific areas. On the one hand, Quercetin (QC) has positive effects as a natural anticancer agent. On the other hand, Fe2O3, as nanoparticles (NP) with clinical properties and high porosity, can be a suitable carrier for drug loading and controlled release. In this study, QC was encapsulated in a synthesized Fe2O3/Starch/Polyvinyl alcohol nanocarrier (Fe2O3/S/PVA NC). Characterization of the NC was done by Fourier transforms infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), vibrating sample magnetometer (VSM), zeta potential and Dynamic light scattering (DLS). The percentage of drug loading (DLE) and encapsulation efficiency (EE) of QC in the NC containing Fe2O3 nanoparticles was 47 % and 86.50 %, respectively, while it was 36 % and 73 % in the NC without Fe2O3. QC profile release in acidic and natural mediums showed controlled release and pH dependency of the NC. Viability of L929 and HepG2 treated cells with the Fe2O3/S/PVA/QC was demonstrated by MTT staining which was in agreement with flow cytometry. The results show that Fe2O3/S/PVA is a suitable NC for the targeted delivery of QC as a drug against HepG2 cancer cells.

The effect of a helmet type, home-use low-level light therapy device for chemotherapy-induced alopecia: study protocol for a randomized controlled trial

BackgroundAlopecia is one of the most common adverse effects of chemotherapy. It reduces the patient’s self-esteem and quality of life and the effect of therapy. Scalp cooling is the only verified current method for prevention but success is not guaranteed, particularly after receiving anthracycline-based combinations.Low-level light therapy has been clinically proven to inhibit the progress of androgenic alopecia. A previous study using human subjects shows limited benefits for low-level light therapy for patients who suffer chemotherapy-induced alopecia but an increase in the number of probes and the optimization of light sources may improve the efficacy. This study determines the efficacy of low-level light therapy for the prevention of chemotherapy-induced hair loss for patients with breast cancer using a randomized controlled trial.MethodsOne hundred six eligible breast cancer patients were randomly distributed into a low-level light therapy group and a control group, after receiving chemotherapy. Subjects in the low-level light therapy group received 12 courses of intervention within 4 weeks. Subjects in the control group received no intervention but were closely monitored.The primary outcome is measured as the difference in the hair count in a target area between the baseline and at the end of week 4, as measured using a phototrichogram (Sentra scalp analyzer). The secondary outcomes include the change in hair count at the end of week 1, week 2, and week 3 and hair width at the end of week 1, week 2, week 3, and week 4, as measured using a phototrichogram, and the change in distress, the quality of life, and self-esteem due to chemotherapy-induced alopecia, at the end of week 4, as measured using a questionnaire.DiscussionThis study improves cancer patients’ quality of life and provides clinical evidence.Trial registrationRegistered at ClinicalTrials.gov—NCT05397457 on 1 June 2022.

Prevention of Taste Alterations in Patients with Cancer Receiving Paclitaxel- or Oxaliplatin-Based Chemotherapy-A Pilot Trial of Cannabidiol.

Taste alteration is a common adverse effect of chemotherapy. This study aimed to investigate the effect of cannabidiol (CBD) on Lean Body Mass (LBM), and taste alterations during oxaliplatin- or paclitaxel-based chemotherapy. LBM was estimated by bioelectrical impedance analysis (BIA), and taste perception was evaluated by a randomized sensory test of six samples: sweet, salt, and umami, all in weak and strong concentrations. Taste perceptions were scored on visual analog scales. Patients in the intervention group received oral CBD 300 mg/day for 8 days; patients in the control group did not. Patients were followed for three cycles of chemotherapy. Twenty-two/ten patients (intervention/control group) were eligible. No effects on LBM were demonstrated. At baseline, the control group was able to differentiate between weak and strong saltiness and weak and strong sweetness but lost this ability after three cycles of chemotherapy. At baseline, the intervention group was unable to differentiate between the concentrations but gained the ability to significantly differentiate between weak and strong sweetness (p = 0.03) and weak and strong saltiness (p = 0.04) after three cycles of chemotherapy and treatment with CBD. CBD may improve patients' ability to differentiate taste strengths during chemotherapy.

The clinical research study for fosaprepitant to prevent chemotherapy-induced nausea and vomiting: A review.

In recent years, chemotherapy-induced nausea and vomiting (CINV) has become the most common adverse effect of chemotherapy in oncology patients. The CINV may reduce the quality of life in mild cases, or even make the patients resist or delay further treatment. Fosaprepitant is a newly marketed neurokinin-1 receptor antagonist (NK-1RA), which can be combined with 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs) and dexamethasone to prevent chemotherapy-induced vomiting. The dimeglumine salt form of fosaprepitant can be utilized as an intravenous injectable drug, which surpasses aprepitant's oral admistration limits. Fosaprepitant is effective and safe in the control of CINV in cancer patients receiving highly emetogenic chemotherapy (HEC), and may be an alternative option for antiemetic therapy. In general, fosaprepitant is worthy of clinical promotion and has a large market potential. This article reviews the clinical studies on fosaprepitant conducted in recent years, with the aim of providing a basis for the rational clinical selection of antiemetic drugs.

LBODP011 Pembrolizumab Induced Hypophysitis And Resultant Isolated ACTH Deficiency Presenting As Secondary Adrenal Insufficiency.

Abstract Introduction Pembrolizumab is a novel human immunotherapeutic monoclonal antibody directed against PD-1 (programmed death receptor 1). It has been approved by the FDA for treatment of many malignancies including breast cancer. Although it has improved survival for many oncological conditions, it has been linked to a variety of endocrinopathies. We present a case of Pembrolizumab induced hypophysitis with isolated ACTH deficiency presenting as secondary adrenal insufficiency. Case presentation A 36 year old female with a history of breast cancer treated with chemotherapy and surgery, presented with intractable nausea and vomiting. She reported not being able to keep anything down for 4-5 days and had experienced multiple episodes of non-bilious, non-bloody emesis. She endorsed dizziness, but denied fever, chills, shortness of breath, abdominal pain, or problems with urination/bowel movements. She had been treated with Pembrolizumab with the last dose being 4 months prior to presentation. On arrival, vitals included temperature 98.4 F, BP 104/62 mm Hg, Heart rate 104 bpm, RR 16 with SpO2 100%. Labs were significant for WBC count 3.65 K/uL (3.81 - 8.94), Eosinophils 10.4% (0.1 - 6; she was noted to have eosinophilia prior to presentation), Hemoglobin 11.6 g/dL (11 - 14.9), Sodium 140 mmol/L (136-145), Potassium 3.4 mmol/L (3.4 - 5.1), Glucose 57 mg/dL (70 - 100), Lactate 0.7 mmol/L (0.2 -2), Lipase 23 U/L (13 - 60), Urine HCG negative, Urinalysis negative for nitrites and leukocyte esterase, TSH 1.22 uIU. ml (0.5 -5.7) and AM cortisol 0.4 ug/dL (6 - 18.4). Endocrinology was consulted and further work up was sought: ACTH <5 pg/ml (7.2 - 63) and Cortisol 30 - 60 minutes after cosyntropin stimulation 3.6 ug/dL. Prolactin, free T4, FSH and LH were within normal limits. MRI brain showed a prominent pituitary gland with enhancement and interval loss of posterior pituitary bright spot representing lymphocytic hypophysitis. She was started on Solu-Cortef and her symptoms resolved. She was discharged on hydrocortisone with education on sick day rules for secondary adrenal insufficiency. Discussion Adrenal insufficiency secondary to immunotherapy is a rare, emergent and dangerous condition. The key to successful management is early recognition. In patients treated with immunotherapy agents, non-specific symptoms such as nausea, vomiting, fatigue (which are common adverse effects of chemotherapy) should prompt urgent evaluation with hormonal workup. Evidence suggests that eosinophilia may be an early indicator before the onset of symptoms which was evident in our case. Radio-graphic imaging is helpful for diagnosis. Treatment entails high dose corticosteroids for acute crisis followed by physiological maintenance dosing. Patients should be educated on sick day rules for adrenal insufficiency. Presentation: No date and time listed

The Effect of Traditional Korean Medicine for Chemotherapy-Induced Hand-Foot Syndrome in Cancer Patients: Review

Objectives: Hand-foot syndrome (HFS) is a common adverse effect of chemotherapy in cancer patients. This review synthesizes research results to assess the effect of traditional Korean medicine (TKM) on HFS in cancer patients.Methods: Four databases (PubMed, The Cochrane Central Register of Controlled Trials, Research Information Sharing Service, China National Knowledge Infrastructure) were searched for randomized controlled trials (RCTs) to assess the effects of TKM on HFS. The effects and quality of RCTs were assessed with the Cochrane risk of bias (ROB) tool.Results: Six RCTs met our study criteria. In all six, TKM showed improvement in HFS symptoms as well as quality of life scores when compared to the control group. However, the methodological quality of RCTs was relatively low due to the unclear or high ROB.Conclusions: TKM would be helpful to patients with HFS after chemotherapy. To clarify the clinical efficacy of TKM, well-designed studies are required in the future.

Peripheral Neuropathy and Pain Caused by Cancer Chemotherapy

Peripheral neuropathy and pain are common adverse effects of chemotherapy, which incidence are rising significantly commensurate with extension of survival period in cancer patients. Chemotherapy-induced peripheral neuropathy is caused by most commonly used chemotherapeutic agents including platinum compounds, taxenes, proteasome inhibitors, thalidomide, and vinca alkaloids. Management of neuropathy and pain caused by chemotherapy is still challenging due to there is no proven therapies and preventive methods. The pain and its impact are becoming a main deterioration factor in quality of life and economic burden in our society. We review the mechanism, clinical characteristics, updated evidence of possible management of neuropathy and pain caused by traditional chemotherapeutic agents for contributing to the application of clinicians in their actual medical environment.

The Perception of Chemotherapy-Induced Alopecia in Cancer Patients Currently Undergoing Treatment

Background: Chemotherapy-induced alopecia (CIA) is a common adverse effect of chemotherapy. 8% of patients consider declining chemotherapy due to CIA risk.Objective: To determin whether cancer patients who are actively receiving chemotherapy are interested in preventing or treating CJA.Materials and Methods: This is a survey-based, cross-sectional study of cancer patients undergoing chemotherapy infusion at a tertiary medical center. Data including demographics, cancer diagnosis, medical literacy, quality of life, hair quality satisfaction, and costs patients were willing to accrue for CIA prevention/treatment were gathered.Results: Sixty-two adults were enrolled, mostly 55 to 64 years of age, female (72.6%), and White (63.8%). Many patients were diagnosed with malignancies associated with a high rate of morbidity-mortality including ovarian, lung and pancreatic. In our cohort, all patients would not decline cancer treatment based on CIA risk. 94.6% of patients were unwilling to risk cancer recurrence, 80.9% additional side effects, 55.8% extra time outside of infusion and 47.9% to pay out-of-pocket for CIA prevention/treatment.Conclusions: Patients with high cancer disease burden will not decline current treatment due to CIA risk. In addition, they are not willing to sustain additional discomfort, cost or time to prevent or treat CIA.

Cognitive Deficits in Cancer Patients with Haematological Malignancies

Cognitive deficits are one of the most common adverse effects of chemotherapy (CHT). Previous reports suggest that this is due to the so-called chemo brain syndrome, the symptoms of which manifest mainly as impairments in executive functions, speed of information processing, memory, attention, and motor speed. However, empirical evidence for these manifestations is currently ambiguous. The research group consisted of 26 cancer patients with haematological malignancies who had undergone chemotherapy treatment. Cognitive performance was measured by two screening cognitive tests, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Test (MoCA). MMSE detected cognitive deficits in 34.6% of patients whereas MoCA identified mild or moderate cognitive impairment in up to 80.7% of patients. The highest error rates were found in tasks focused on memory, attention, spatial orientation, executive functions, and abstraction. Cognitive deficit progressed with age, but not with duration of therapy. Deficits in cognitive functions occur in a considerable number of patients after CHT, although the diagnosis depends on the sensitivity of the detection method. Screening scales usually provide the first indication of impaired cognitive functioning and may indicate the need for further neuropsychological examination. Early diagnosis of reduced cognitive functions is a prerequisite for effective psychological intervention to help patients cope with the undesirable effects of chemotherapy treatment more quickly.Key words: chemotherapy - cognitive dysfunction - chemo brain - cognitive screening - neuropsychological tests - psychology The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 7. 2017Accepted: 24. 8. 2017.

Rebamipide suppresses 5-fluorouracil-induced cell death via the activation of Akt/mTOR pathway and regulates the expression of Bcl-2 family proteins

Oral mucositis is a common adverse effect of chemotherapy that limits the required dose of chemotherapeutic agents. Numerous attempts to mitigate chemotherapy-induced oral mucositis have failed to identify an appropriate treatment. Recently, it has been indicated that rebamipide prevents chemoradiotherapy-induced oral mucositis in patients. However, the details of the underlying mechanism involved in the cytoprotective effect of rebamipide remain obscure. In the present study, we investigated the mechanism behind rebamipide cytoprotective effect in the oral mucosa using primary normal human oral keratinocytes (NHOK cells). We found that rebamipide prevented 5-fluorouracil (5-FU)-induced cell death in NHOK cells. In addition, rebamipide increased the levels of phosphorylated Akt and mTOR, enhanced the Bcl-2 and Bcl-xL expressions, and suppressed the expression of Bax and Bim. This is in contrast to 5-FU-induced suppression of Akt and mTOR activation, Bcl-2 and Bcl-xL expressions, and the enhanced expression of Bax and Bim. These findings suggest that rebamipide can potentially be used for the protection of oral mucosa from chemotherapy-induced mucositis. This is the first study that elucidates the specific molecular pathway for the cytoprotective effect of rebamipide.

Rapamycin Prevents cyclophosphamide-induced Over-activation of Primordial Follicle pool through PI3K/Akt/mTOR Signaling Pathway in vivo

BackgroundPrimordial follicular depletion has thought to be a common adverse effect of chemotherapy especially for female of reproductive age. The study aimed to evaluate the protective effect of rapamycin on the primordial follicles and its potential mechanism for patients receiving chemotherapy.Methods8-week old BALB/c female mice were randomly assigned into four groups (control; rapamycin; cyclophosphamide; and rapamycin combined with cyclophosphamide). Hematoxylin staining, immunohistochemical, TUNEL, western blotting and ELISA were employed to assess inter-group differences using Student’s t-test and Mann-Whitney test.ResultsCyclophosphamide depleted the follicular reserve and induced the phosphorylation of the key proteins of PI3K/Akt/mTOR pathway in mice in a dose-dependent manner. Co-treatment with rapamycin significantly reduced primordial follicle loss at all cyclophosphamide dose groups and prevent the follicle growth wave caused by cyclophosphamide treatment (P < 0.05). TUNEL staining showed that no apoptosis occured in the primordial follicles in all groups and fewer apoptosis in large growing follicles were observed in ovaries from rapamycin + cyclophosphamide group compared to that received cyclophosphamide alone. Serum anti-Müllerian hormone (AMH) was significantly reduced in cyclophosphamide alone group, in contrast to the normal level in rapamycin + cyclophosphamide group. Compared to p-Akt/Akt and p-mtor/mtor, p-rps6/rps6 was significantly decreased in rapamycin + cyclophosphamide group (P < 0.05), indicating that rapamycin attenuated the increased level of phosphorylation of rpS6 after cyclophosphamide treatment.ConclusionsRapamycin can prevent the primordial follicle activation induced by cyclophosphamide through PI3K/Akt/mTOR signaling pathway and thus plays a role in preserving the follicle pool. These results suggest that rapamycin may be an effective protection for ovarian function during chemotherapy, which means a new nonsurgical application for protection of ovarian reserve and prevention of POF.

Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy

The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy. We demonstrate differential sensitivity of neurons to mechanistically distinct classes of chemotherapeutics. We also show a dose-dependent reduction of electrical activity as measured by mean firing rate of the neurons following treatment with paclitaxel. We compared neurite outgrowth and cell viability of iPSC-derived cortical (iCell® Neurons) and peripheral (Peri.4U) neurons to cisplatin, paclitaxel and vincristine. Goshajinkigan, a Japanese herbal neuroprotectant medicine, was protective against paclitaxel-induced neurotoxicity but not oxaliplatin as measured by morphological phenotypes. Thus, we have demonstrated the utility of human iPSC-derived neurons as a useful model to distinguish drug class differences and for studies of a potential neuroprotectant for the prevention of chemotherapy-induced peripheral neuropathy.

Bone marrow response as a potential biomarker of outcomes in glioblastoma patients.

OBJECTIVE Glioblastoma (GBM) is a highly aggressive malignancy that requires a multidisciplinary therapeutic approach of surgery, chemotherapy, and radiation therapy, but therapy is frequently limited by side effects. The most common adverse effect of chemotherapy with temozolomide (TMZ) is myelosuppression. It remains unclear whether the degree of bone-marrow suppression might serve as a biomarker for treatment outcome. The aim of the current study was to investigate whether the degree of bone-marrow toxicity in patients treated with TMZ correlates with overall survival (OS) and MRI-based time to progression (progression-free survival [PFS]). METHODS Complete blood counts and clinical and imaging information were collected retrospectively from 86 cases involving GBM patients who had completed both radiation therapy and at least 6 monthly cycles of chemotherapy with TMZ. RESULTS Using a multivariate Cox proportional hazard model, it was observed that MGMT promoter methylation, wild-type EGFR, younger patient age at diagnosis, and treatment-induced decreases in white blood cell counts were associated with improved OS. The 2-year survival rate was 25% and 58% for patients with increases and decreases, respectively, in white blood cell counts from baseline over 6 months of TMZ treatment. Consistent with the literature, IDH mutation and MGMT promoter methylation were associated with better PFS and OS. IDH mutation and MGMT promoter methylation were not correlated with changes in peripheral red blood cell or white blood cell counts. CONCLUSIONS Decreases in white blood cell counts might serve as a potential biomarker for OS and PFS in malignant glioma patients treated with radiation therapy and TMZ. It remains unclear whether treatment-induced changes in white blood cell counts correlate with drug-induced antitumor activity or represent an independent factor of the altered local and systemic tumor environment. Additional studies will be needed to determine dose dependence for chemotherapy based upon peripheral blood counts.

Intestinal permeability to iohexol as an in vivo marker of chemotherapy-induced gastrointestinal toxicity in Sprague-Dawley rats.

PurposeGastrointestinal toxicity is the most common adverse effect of chemotherapy. Chemotherapeutic drugs damage the intestinal mucosa and increase intestinal permeability. Intestinal permeability is one of the key markers of gastrointestinal function and measuring intestinal permeability could serve as a useful tool for assessing the severity of chemotherapy-induced gastrointestinal toxicity.MethodsMale Sprague–Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg) or irinotecan (200 mg/kg). Clinical signs of gastrointestinal toxicity were assessed daily by weighing the animals and by checking for diarrhea. After 48 h, intestinal permeability to iohexol was measured in vivo by giving the animals 1 ml of 647 mg/ml iohexol solution by oral gavage and collecting all the excreted urine for 24 h. All of the animals were euthanized 72 h after drug administration and tissue samples were harvested from the jejunum and colon.ResultsAll chemotherapeutics caused significant body weight loss and diarrhea. Intestinal permeability to iohexol was also increased in all treatment groups and histological analysis revealed significant intestinal damage in both jejunum and colon. Iohexol permeability correlated with the severity of clinical signs of gastrointestinal toxicity and with acute colonic injury.ConclusionsChemotherapeutic drugs, such as 5-fluorouracil, oxaliplatin, and irinotecan, increase intestinal permeability to iohexol. Measuring intestinal permeability to iohexol could provide a simple marker for assessing chemotherapy-induced gastrointestinal toxicity.Electronic supplementary materialThe online version of this article (doi:10.1007/s00280-016-3150-3) contains supplementary material, which is available to authorized users.

The University of Michigan Sarcoma Survivorship Clinic: Preventing, Diagnosing, and Treating Chronic Illness for Improved Survival and Long-Term Health.

The Children's Cancer Survivorship Study reports more chronic illnesses in sarcoma survivors than other pediatric cancers. Chemotherapy and radiation put survivors at risk for developing chronic illnesses, including heart disease, diabetes, hypertension, and kidney failure. Sarcoma survivors may have a reduced life expectancy and signs of heart disease in their 30s and 40s. Since these medical problems occur much later in the general population, they often go undetected or misdiagnosed in sarcoma survivors, creating delays in intervention and treatment. The good news is that these chronic illnesses can often be prevented or minimized. The most common adverse effect of chemotherapy and radiation is coronary artery disease (CAD). CAD has a number of risk factors, including hypertension, diabetes, obesity, and dyslipidemia. These risk factors are modifiable with lifestyle changes, including diet and exercise, and/or pharmacological intervention. By identifying and managing risk factors like hypertension early, we in turn reduce the risk for CAD and prolong survival. This is well established in the general population; there is no reason a priori not to apply it to sarcoma survivors. Sarcoma survivors should be followed by physicians who understand the late effects and outcomes of sarcoma treatment. The University of Michigan Sarcoma Survivorship Clinic provides long-term care for sarcoma survivors by preventing, diagnosing, and treating the adverse long-term physical and psychological effects associated with sarcoma survivorship.

Effect of honey on febrile neutropenia in children with acute lymphoblastic leukemia: A randomized crossover open-labeled study

ObjectivesFebrile neutropenia (FN) is a common adverse effect of chemotherapy. Current management of FN is expensive and may induce side effects. Honey, as a natural honeybee product, has antioxidant, antimicrobial, immunomodulator and anticancer effects. Additionally, honey is not expensive. The aim of this study is to test the effects of a 12-week honey consumption on children with acute lymphoblastic leukemia (ALL) particularly with regard to FN. DesignA randomized crossover clinical trial. Forty patients of both sexes, aged 2.5–10 years, were randomized into two equal groups [intervention to control (I/C) and control to intervention (C/I)]. SettingChildren Hospital of Ain Shams University-Cairo-Egypt. The dietary intervention consisted of honey in a dose of 2.5g//kg body weight per dose twice weekly for 12 weeks. Main outcome measureFebrile neutropenia in terms of frequency and duration of hospital admission. ResultsThe intervention resulted in a significant decrease of FN episodes, the number of patients admitted with FN and the duration of hospital stay. Also, honey consumption improved the levels of hemoglobin and did not produce any serious side effect. As a possible effect of honey withdrawal in the I/C group, the Hb%, the absolute neutrophil count and the platelet count decreased. ConclusionHoney intervention in a group of children with ALL resulted in positive effects on FN and hematologic parameters. Further studies that include a larger number of patients are recommended to confirm that honey, has beneficial effects, as a complementary agent, in children with ALL.