Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer:A critical update

Gastrointestinal toxicities(GIT), including oral mucositis,nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient's quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient's outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient's compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer.

Contact toxicities of imidacloprid on rice brown plant hopper(Nilaparvata lugens Stal)

Rice brown planthopper (BPH) (Nilaparvata lugens Stal, ) which occurs 4 generations within one year in Jiangsu Province has become a serious pest and causes loss of yield on rice every year in this region. The contact toxicities of imidacloprid and methamidophos to rice BPH were tested by means of immerse topical application method and a field trial from 1993 to 1994. A randomized complete design was laid out in 6 treatments with three replications.

Effects of selenomethionine on acute toxicities from concurrent chemoradiation for inoperable stage Ⅲ nonsmall cell lung cancer

AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine(SLM) with concurrent chemoradiation(CCRT) for Stage Ⅲ non-small cell lung cancer(NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use.METHODS: Sixteen patients with stage Ⅲ NSCLC were accrued to this single arm, phase Ⅱ study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly Ⅳ paclitaxel 50 mg/m2 followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment. RESULTS: No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients(19%), pneumonitis in 0, leukopenia in 2(12.5%), and anemia in 1(6%); the latter two were significantly reduced when compared to the protocolstated expected rate of 35%(P = 0.045 for leukopenia, and P < 0.01 for anemia). Median overall survival was 14.9 mo and median failure-free survival was 9 mo(95%CI: 3.3-21.5).CONCLUSION: There may be some protective benefit of selenium in the setting of CCRT for inoperable NSCLC. The data suggests decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted.

Determination of the Toxicities of 16 Halogenated Benzenes to Photobacterium Phosphoreum and 2D- and 3D-QSAR Studies

In this paper we take photobacterium phosphoreum （T3） as the experimental bacteria, and determine the half-inhibitory concentration （-1gEC50） against the photobacterium phosphoreum of 16 halogenated benzenes. Using B3LYP method of DFT in the Gaussian 03 program, we obtain the structural and thermodynamic descriptors of 16 halogenated benzenes by fully-optimized calculation at the 6-311G＊＊ level. Taking the structural and thermodynamic descriptors as theoretical descriptors, the 2D QSAR model （R2 = 0.983） was established, which can be utilized to predict -lgEC50 of halogenated benzene according to the corrected linear solvation energy theory based on the experimental data of-lgECs0. In addition, the relationship between the toxicity and 3D spatial structure of the compound is studied by comparing the molecular similarity index analysis （CoMSIA） of 3D-QSAR method. By cross validation, the correlation coefficient q2 of CoMSIA model is 0.687, and the conventional correlation coefficient R2 = 0.958. The model is stable and reliable with great predictive ability. The 3D-QSAR model shows that the toxicity of halogenated benzene compound is mainly affected by the characteristics of hydrophobie field of the substituted halogens.

Comparative clinical study of conjunctival toxicities of newer generation fluoroquinolones without the influence of preservatives

AIMTo compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives.METHODSIn a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a primary pterygium were enrolled, and divided randomly into three groups (levofloxacin 0.5%, gatifloxacin 0.3%, and moxifloxacin 0.5%). After pterygium surgery with the same conjunctival autograft technique, each patient maintained a regimen with a randomly assigned fluoroquinolone eye drop. Patients were examined every other day after surgery until the epithelium had completely healed. Photos were taken and used to measure the area of residual epithelial defects. Conjunctival healing time and speed (initial defect area/healing time (mm2/d) compared in each group using Kruskal-Wallis tests.RESULTSThere were no significant differences in mean age, gender, and conjunctival defect size of the donor site between these groups. However, the mean of conjunctival healing time and speed were statistically different in each group. The mean of conjunctival epithelial healing time was 8.93±2.69d (levofloxacin group), 10.31±2.96d (gatifloxacin group), and 13.50±4.10d (moxifloxacin group), P=0.006. The mean conjuctival epithelial healing speed was 6.18±1.39 mm2/d (levofloxacin group), 5.52±1.68 mm2/d (gatifloxacin group), and 4.40±1.30 mm2/d (moxifloxacin group), P=0. 003.CONCLUSIONWithout the influence of preservatives, levofloxacin and gatifloxacin might be less toxic to the regeneration of conjunctival epithelial cells and cause a faster conjunctival wound healing relative to moxifloxacin.

Acute Toxicities of Potassium Permanganate, Formalin, and Lugol's Iodine Solution to a Marine Ciliate, Pleuronema coronatum (Ciliophora, Scuticociliatida)

Acute toxicities of potassium permanganate, formalin, and Lugol’s iodine solution to a commonly occurred marine ciliate Pleuronema coronatum (Ciliophora, Scuticociliatida) were measured. Linear regression analysis of the results highlighted the close relationships between doses of the medicines and mortalities of the organisms, thus providing a capability to predict toxicity effects from the dose. Toxic effects of the medicines on the ciliates were described in the present paper, and the median lethal concentrations (LC 50 values) were given. Results of measurements indicated that 2 h-LC 50 and 12 h-LC 50 values of formalin on P. coronatum were 59.00×10 -6 and 43.57×10 -6, while those of Lugol’s solutions were 90.13 and 67.84×10 -6 respectively. The tolerance of P. coronatum to formalin is apparently lower than that to Lugol’s iodine solution and potassium permanganate is a suitable medicine to kill ciliates in short time.

ACUTE TOXICITIES OF COPPER, CADMIUM AND Cu: Cd MIXTURE TO LARVAE OF THE SHRIMP PENAEUS PENICILLATUS

This study showed Iethal concentrations (LC) of copper for Peneaus penicillatus at various stages ofits Iife cycle were 1000μg/L for nauplii, 1000μg/L for Zoea I, 2000μg/L for Zoea Il, 2500μg/Lfor Zoea III, 3000μg/L for Mysis I, II and III and that for almost 100% mortality for postlarvae was3000μg/L. For cadmium LC were 100μg/L for nauplii, 500μg/L for Zoea l, 1000μg/L forZoea II, 2000μg/L for Zoea III, 2500μg/L for Mysis I and 3500μg/L for Mysis II, III andpostlarvae. For tmixture of both metals, LC were 400μg/L for nauplii, 1000 μg/L for nauplii, 1000μg/L for Zoea I,2000μg/L for Zoea II and 3000μg/L for Mysis I, II, III and post larvae.

Plantain-based diet modulates atrazine-induced testicular toxicities in rats

Objective:To assess the potential of plantain-based diet in modulating testicular toxicities in rats exposed to atrazine.Methods:The plantain-based diet at 50%,25% and 12.5% were prepared from the basal diet by substituting the corn starch with plantain fruit pulp flour at different percentages.Wistar rats were fed plantain-based diet in varying concentrations ranging from 12.5% to 50% of the basal diet for 21 days before or after atrazine treatment in a two-phase experiment:preventive and therapeutic phases.The therapeutic model(n=35)had seven groups with 5 rats each,including the control,atrazine,atrazine recovery,atrazine plus plantain-based diet 50%,25%,12.5%,and atrazine plus quercetin groups.The preventive model(n=30)had six groups of 5 rats,consisting of the control,atrazine,50%,25%,12.5% plantain-based diet plus atrazine,and quercetin plus atrazine groups.Gonadal hormones(testosterone,luteinizing hormone and follicle-stimulating hormone),sperm parameters(sperm motility,viability,morphology and concentration),and testicular function indices(protein,cholesterol,glycogen,acid phosphatase,alkaline phosphatase and lactate dehydrogenase)were measured.Results:The gonadal hormones,sperm characteristics,and testicular function indices of the rat testis decreased significantly in the atrazine group alongside degeneration of the histoarchitecture.However,plantain-based diet restored the gonadal hormone concentrations,semen parameters,and testicular function indices in both the preventive and therapeutic models.Conclusions:Treatment with plantain-based diet protects against rat testicular toxicity caused by atrazine via the modulation of gonadal hormones,sperm quality,testicular function index as well as histoarchitecture of rat testes.

Simvastatin nanoliposome induces myocardial and hepatic toxicities due to its absorption enhancement in mice

Nanoliposome is a useful dosage form to increase solubility and absorption of simvastatin(SMV), and consequently improves its therapeutic effects. However, in vivo toxicity of SMV could also be elevated accompanied by the absorption enhancement, which is a decisive factor for the clinical application of SMV nanoliposome(SMV-Lipo), but has not been studied systematically and reported so far. In this study, organ toxicity of SMV-Lipo was evaluated in mice in the presence and absence of isoproterenol and compared to those of free SMV. Results demonstrated that compared to free SMV, the SMV-Lipo administrated at an equal dose of 25 mg/kg/d led to severe myocardiotoxicity, hepatotoxicity at baseline and more pronounced liver injury with elevation of alanine aminotransferase. In addition, muscular adverse effect was also observed in SMV-Lipo treated group but not in SMV group. Pharmacokinetic studies revealed that compared to free SMV, the SMV-Lipo administration significantly improved the plasma SMV concentration, and the oral bioavailability was 6.5 times of free SMV. Notably, when the dosage of free SMV increased to 50 mg/kg/d, yielding the comparable plasma concentration as SMV-Lipo given at 25 mg/kg/d, the myocardiotoxicity was observed in free SMV treated mice as well, which further confirmed that the enhanced absorption of SMV by the nanoliposomal formulation resulted in more severe myocardiotoxicity than the equal dose of free SMV.

Acute and sub-acute toxicities of hydroalcoholic extract of Allium affine aerial parts in rats

Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,animals orally received the limit test dose of 2000 mg/kg of A.affine extract and were observed for 2 weeks.For sub-acute toxicity study,rats were orally treated with 125,250,and 500 mg/kg/day of the extract over 28 days,and hematological,biochemical,and histological evaluations were then conducted.Results:All rats were alive with normal body weight gain over 14 days,with LD50˃2000 mg/kg.No abnormality in body weight changes but significant increases in the relative weight of spleen and lung were detected after administration of the highest dose of extract for 28 days in sub-acute assay.Hematological analysis showed prominent elevations in total white blood cells in male rats and neutrophils count in female rats after exposure to 500 mg/kg of A.affine extract.In biochemical evaluations,significant increases in serum creatinine level(female rats,250 and 500 mg/kg)and in aspartate aminotransferase(male and female rate,500 mg/kg)and alanine aminotransferase(male,250 and 500 mg/kg and female,500 mg/kg)activities,however,notable decreases in serum blood glucose(male rats,125 and 500 mg/kg),triglycerides(male rats,500 mg/kg and female rates,250 mg/kg),and low-density lipoprotein cholesterol levels(male,250 mg/kg)were found.Histological examinations presented slight portal inflammation in liver tissue,moderate pneumocyte hyperplasia,congestion and peri-bronchial inflammation in lung tissue,and mild histiocytosis and lymphoid follicular activation in spleen tissue after exposure to 500 mg/kg of A.affine extract in male and female animals.Conclusions:The present investigation reveals the safety of A.affine extract at doses of lower than 250 mg/kg in rats and monitoring of lung,spleen,and liver functions is suggested during excessive and prolonged uses.

Factors associated with increased incidence of severe toxicities following yttrium-90 resin microspheres in the treatment of hepatic malignancies

AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (90Y) microspheres.METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following 90Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity.RESULTS: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043).CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for 90Y microsphere therapy.

Evaluation of Acute and Sub-Acute Oral Toxicities of Momordica foetida Schumach. (Cucurbitaceae) Leaves Methanol Extract in Wistar Rats

Momordica foetida is a plant widely used in tropical Africa to manage gastroenteric diseases. Previous studies demonstrated interesting antibacterial activity against human pathogenic bacteria. However, the security or toxicity of methanol leaf extract has not been determined yet. The aim of this study was to evaluate the acute and sub-acute toxicity of the leaf extract of Momordica foetida. In the acute toxicity study, a single oral dose of 5000 mg/kg body weight was administered to rats which were observed for 14 days in order to identify signs of toxicity or death. In the sub-acute toxicity, the animals were treated with 250, 500 and 1000 mg/kg of the extract for 28 consecutive days. Body weights and behavior were noted throughout the experiment. Upon treatment, blood and urine were collected for hematological and biochemical analysis. Liver, lungs, heart, kidneys, testes and ovaries were analyzed for relative weights and histopathology. The acute toxicity study of M. foetida leaf extract revealed no signs of toxicity related to the treatment, indicating that the median-lethal-dose (LD50) value is greater than 5000 mg/Kg of body weight. In the sub-acute toxicity assay, the extract did not affect the general behavior of animals, meanwhile, it led to a significant increase in the levels of red blood cells, platelets, hemoglobin, granulocytes and Mid-Cells (MIDs). Biochemical parameters showed an increase in total cholesterol, HDL cholesterol, serum urea, serum and urinary glucose and a decrease in urinary proteins, serum creatinine, urinary urea levels, serum activities of AST, ALT and proteins levels, as well as increases in lung, spleen and ovaries relative weight were noticed, all compared to control animals. Histological analysis revealed a normal architecture of kidneys, liver, heart, lung, ovaries and testes. This study provides valuable data on the safety of per os administration of Momordica foetida leaf methanol extract that could be very useful for future assays.

Management of skin toxicities during panitumumab treatment in metastatic colorectal cancer

BACKGROUND Anti-epidermal growth factor receptor therapy is associated with skin adverse events not previously reported with conventional chemotherapy. Prophylactic actions are recommended, but routine clinical management of these toxicities and their impact on quality of life remain unknown. AIM To assess the dermatological toxicities reported after panitumumab initiation, their impact on the quality of life and the clinical practices for their management. METHODS Patients included in this prospective multicenter observational study were over 18 years of age and began treatment with panitumumab for wild-type KRAS metastatic colorectal cancer. The incidence of dermatological toxicities, clinical practices for their management and impact on quality of life were recorded during a 6-mo follow-up. RESULTS Overall, 229 patients (males, 57.6%;mean age, 66.2 years) were included. At day 15, 59.3% of patients had dermatological toxicity;the rate peaked at month 2 (74.7%) and decreased at month 6 (46.5%). The most frequent dermatological toxicities were rash/acneiform rash, xerosis and skin cracks. At least one preventive treatment was administered to 65.9% of patients (oral antibiotics, 84.1%;emollients, 75.5%;both, 62.9%). The rates of patients who received at least one curative treatment peaked at month 2 (63.4%) and decreased at month 6 (44.8%). The impact of the dermatological toxicities on quality of life was limited as assessed with Dermatology Life Quality Index scores and inconvenience visual analogic scale score. The rates of topical corticosteroids administration and visits to specialists were low. CONCLUSION The rates of the different skin toxicities peaked at various times and were improved at the end of follow-up. Nevertheless, their clinical management could be optimized with a better adherence to current recommendations. The impact of skin toxicities on patient’s quality of life appeared to be limited.

Studies on the Analgesic Activity and Acute Toxicities of Bidens alba(L.) DC

[Objectives]This study was conducted to investigate the analgesic effects and acute toxicities of Bidens alba (L.) DC.[Methods]The alcohol extract of B.alba (L.) DC was extracted and separated with petroleum ether and chloroform successively.The acute toxicities of the two extracts on mice were measured,and then the analgesic effects were measured with writhing pain model induced by acetic acid.[Results]No mice died when the crude dosages of B.alba (L.) DC from petroleum ether extract and chloroform extract were 5 016 and 5 100 mg/kg,respectively.When the petroleum ether extract was 60.0 mg/kg,the percentage of twisted mice induced by acetic acid was 40%,the analgesic rate was 77.5%,and the time of the first writhing was (294.0±165.8) s;when the chloroform extract was 20.0 mg/kg,the percentage of twisted animals was 55.6%,the analgesic rate was 51.5%,and the time of the first writhing was (273.8 ±153.4) s;and when the chloroform extract was 4.0 mg/kg,the percentage of twisted animals was 40%,and the analgesic rate was 62.1%,and the time of the first writhing was (370.6±231.3) s.[Conclusions]The petroleum ether extracts and chloroform extracts of B.alba (L.) DC have good analgesic effects and no acute toxicities.

Genetic Polymorphisms and Toxicities of First-Line Antituberculosis Drugs: Systematic Review of the Literature

Introduction: Polymorphisms are the main genetic factors associated with toxicities of antituberculosis drugs. This literature review summarizes the polymorphisms of the genes that code for the enzymes of the metabolism of antituberculosis drugs and their transmembrane transporters. Some mechanisms of drug-associated toxicities and strategies for their management have also been described in this review. Methods: The bibliographic searches were exclusively carried out in PubMed, over a period of ten years (2010-2020). The search terms were the words “toxicity + antituberculosis drug + one or two word(s) among the following: polymorphism, genetics, mutation, SNP, HLA or haplotype”. Publications in English or French, relating to the various toxicities associated with first-line anti-tuberculosis drugs (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide) administered to patients with pulmonary tuberculosis, extrapulmonary tuberculosis or co-infected with TB/HIV were included in this review. Duplicates, in vitro, in silico or drug-induced toxicity studies other than antituberculosis drugs and genetic mutations of Mycobacteria strains were not included. Results: The studies selected and included were case reports, cohort studies, original research, systematic reviews and meta-analyses on human subjects of different ethnic origins. Hepatotoxicity is the most common toxicity associated with NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms in patients on antituberculosis drugs. Other forms of toxicity, less frequent, occurring in certain patients under concomitant treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), antiretrovirals (ARVs), antibiotics or antiepileptics have also been identified. Conclusion: The genetic polymorphisms associated with the toxicities of antituberculosis drugs concern both the main enzymes of the metabolic pathways (NAT2, CYP2E1, GST) and the transmembrane transporters (SLCO1B1 and ABCB1). Other genetic polymorphisms (TXNRD1, SOD2, TYMP) have been suspected but their mechanisms are not yet well understood.

Common toxicities and objective response rate in metastatic colorectal cancer patients treated with irinotecan based regimens

Objective： The aim of our study was to investigate if common toxicities are correlated to objective response rate （ORR） in metastatic colorectal cancer （mCRC） patients treated by irinotecan based regimens. Methods： Univadate and multivariate logistic regression analyses were performed to evaluate correlations between common toxicities and binary ORR in 106 mCRC patients from a prospective cohort treated with irinotecan based regimens. Results： The most frequent severe toxicities （Grade 3/4） were as follows： neutropenia （27.4%）, diarrhea （16.9%）, leucopenia （12.6%）, vomiting （3.2%） and thrombocytopenia （2.1%）. Thrombocytosis was observed in 25 （26.3%） patients. ORR was 25.3%. Thrombocytopenia （P = 0.014）, line of chemotherapy （P = 0.028） and thrembocytosis （P = 0.033） were correlated with ORR in univariate analysis. In multivariate analysis, thrombocytopenia （odds ratio [OR] = 8.600, 95% confidence interval [CI] = 1.705-43.385, P = 0.009） and first line chemotherapy （OR = 5.155, 95% CI = 1.153-23.256, P = 0.032） positively related to ORR. Conclusion： Threm- bocytopenia may be an indicator of ORR in mCRC patients treated by irinotecan plus 5-fluorouracil/capecitabine. Evidence is not strong enough to prove that irinotecan based regimens-induced diarrhea, leucopenia, neutropenia or vomiting is associ- ated with ORR.

Predictive Factors of Severe Toxicities of Pemetrexed-Containing Chemotherapy in Patients with Non-Squamous Non-Small Cell Lung Cancer

Background: Pemetrexed (PEM) is an efficacious multi-targeted antifolate with acceptable toxicities for non-squamous non-small cell lung cancer (non-Sq NSCLC). However, in the clinical setting, PEM has more severe adverse effects than those reported. The aim of this study was to identify the factors for the toxicities of PEM-containing chemotherapy in non-Sq NSCLC patients in the clinical setting. Patients and Methods: We retrospectively evaluated the factors related to PEM toxicities in chemotherapy-naive patients with non-Sq NSCLC from September 2009 to July 2013 at our hospital. Logistic regression model was used in the univariate and multivariate analyses. Results: In total, 104 patients were analyzed. Grades 3 to 5 hematologic toxicities were frequent and included neutropenia (42%), febrile neutropenia (7%), anemia (18%), thrombocytopenia (17%), and disseminated intravascular coagulation (2%). On multivariate analyses, the predictors were poor performance status (PS) [odds ratio (OR): 4.89, 95% confidence interval (CI): 1.22 - 19.4] and low body mass index (OR: 1.44, 95% CI: 1.05 - 1.98) for febrile neutropenia;concomitant chronic infectious disease (OR: 6.63, 95% CI: 1.59 - 27.5) and bevacizumab use (OR: 3.57, 95% CI: 1.36 - 9.32) for neutropenia;poor PS (OR: 3.02, 95% CI: 1.33 - 6.85) for thrombocytopenia;and low serum albumin level (OR: 0.22, 95% CI: 0.08 - 0.63) for non-hematologic toxicities. Conclusions: In addition to the previously reported predictors of PEM toxicities, the presence of concomitant chronic infectious disease was associated with hematologic toxicities. Patient groups who are not sufficiently evaluated in clinical trials should be carefully monitored for the development of more toxicities than expected.

Association between Subjective Evaluation of Skin Toxicities and Quality of Life in Patients with Lung Cancer Undergoing Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Treatment: A Pilot Study for Developing Skin Toxicity Assessment

Purposes: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) exert satisfactory therapeutic effects in lung cancer patients. However, the resultant skin toxicity can deteriorate patients’ quality of life (QoL). Differences exist in skin toxicity evaluation between patients and clinicians. We aimed to clarify the association between the subjective evaluation of skin toxicities and QoL in lung cancer patients and to establish a document of scale development in the subjective evaluation of skin toxicity. Methods: We used self-administered questionnaires to evaluate 12 lung cancer patients receiving EGFR-TKI treatment. Indices of QoL were generated using the Functional Assessment of Cancer Therapy-Lung and Hospital Anxiety and Depression Scale, and a subjective evaluation questionnaire concerning skin toxicity was completed. The data were collected immediately before treatment initiation and at 4 weeks post treatment. Results: In the subjective evaluation of skin toxicity, four patients (33.3%) were classified as ≥Grade 2 (painful group), experiencing painful pruritus at the emergence site of the skin rash or xerosis. In this group, the QoL scores of physical and emotional aspects declined after treatment. Conversely, patients in the painless group (Grade 0 - 1) demonstrated an improved emotional QoL following treatment (p = 0.028). Conclusions: Lung cancer patients suffering from painful skin toxicity tended to show a decline in the physical and emotional aspects of QoL following EGFR-TKI treatment. The skin toxicity questionnaire was useful from the point of view of a subjective evaluation and could be a powerful assessment tool in future clinical settings with further modification.

Evaluation of Acute and Subacute Toxicities of a Recipe Based on Three Leafy Vegetables in Laboratory Rodents

The consumption of a mixture of leafy vegetables has always been a practice anchored in the dietary habits of the people of Brazzaville. The objective of this study was to evaluate the acute and subacute toxicities of the aqueous extract of the recipe based on three leafy vegetables (Amaranthus hybridus L., Spinacia oleracea, Brassica campestris L.) in laboratory rodents. The aqueous extract of the food recipe was administered orally using a cannula. Regarding acute toxicity, the administration of single doses of 5000 and 10,000 mg/kg to mice had no significant effects on behavior. On the other hand, weight loss was significantly (**p < 0.01) compared to control mice (1 mL/100g). The results on subacute toxicity showed that daily administration of the aqueous extract of the food recipe at a dose of 1000 mg/kg for 21 days in rats resulted in a non-significant weight gain, and caused changes in some biochemical parameters including HDL-cholesterol levels, blood sugar levels and ALAT activity.

Predicting the Time-Dependent Toxicities of Binary Mixtures of Five Antibiotics to Vibrio qinghaiensis sp.-Q67 Based on the QSAR Model

Antibiotics may be exposed in a mixed state in natural environments.The toxicity of antibiotic mixtures exhibits time-dependent characteristics,and data on the time-dependent toxicity of antibiotic mixtures is also relatively lacking.In this study,the toxicities of 45 binary mixtures composed of five antibiotics were investigated against Vibrio qinghaiensis sp.-Q67(Q67)at multiple exposure times(4,6,8,10,and 12 h).Quantitative structure–activity relationship(QSAR)models were developed for predicting the time-dependent toxicities of 45 binary mixtures.The results showed that the best QSAR models presented coefficient of determination(R2)of(0.818–0.913)and explained variance in prediction leave-one-out(Q2LOO)of(0.781–0.894)and predictive ability(Q2F1,Q2F2,Q2F3>0.682,concordance correlation coefficient>0.859).The R2 values of QSAR models outperformed the R2(0.628–0.810)of the conventional concentration addition models and the R2(0.654–0.792)of the independent action models.Furthermore,the QSAR models showed higher R2 and Q2LOO values at 4 h compared to other exposure times.Specifically,the model at the 30%effective concentration(EC30)had R2 of 0.902 and Q2LOO of 0.883,while the model at the 50%effective concentration(EC50)had R2 of 0.913 and Q2LOO of 0.894.The CATS2D_04_DP descriptor was found to be the most dominant and negatively correlated factor influencing the toxicity of mixed antibiotics against Q67 in the nine QSAR models developed over five exposure times.The reduction in the number of DP pharmacophore point pairs with a topological distance of 4 in the represented molecules is the primary cause for the rise in the time-dependent toxicity of the antibiotics against Q67.