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A woman with heavy pre-treated ovarian cancer sought consultation regarding additional treatments. The case raises the vexing question of whether there may be a time in the course of the disease process where it is most appropriate to state further anti-neoplastic therapy will not be of clinical utility.

TiO2 nanotube (NT) arrays have been prepared by anodic oxidation of a Ti sheet, and carbon-deposited TiO2 NT arrays have been prepared by annealing TiO2 NT arrays in carbon atmosphere. The biocompatibility of the as-prepared NT arrays was investigated by observing the growth of osteosarcoma (MG-63) cells on the NT arrays. The application of the TiO2 NT arrays as a drug delivery vehicle was investigated. Both the TiO2 NTs and the carbon-modified TiO2 NTs have good biocompatibility supporting the normal growth and adhesion of MG-63 cells with no need of extracellular matrix protein coating. The one end-opened TiO2 NTs can be easily filled with drugs, working as an efficient drug delivery vehicle.

The crystal structures of lenalidomide [systematic name: (RS)-3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione], C13H13N3O3, (I), an anti­neoplastic drug, and its hemihydrate, C13H13N3O3·0.5H2O, (II), have been determined by single-crystal X-ray diffraction analysis. The overall conformation of the mol­ecule defined by the orientation of the two ring portions, viz. pyridine­dione and isoindolinone, is twisted in both structures. The influence of the self-complementary pyridine­dione ring is seen in the crystal packing of both structures through its involvement in forming hydrogen-bonded dimers, although alternate dione O atoms are utilized. An extensive series of N—H⋯O hydrogen bonds link the dimers into two-dimensional supra­molecular arrays built up from infinite chains. The water mol­ecule in (II) has a cohesive function, connecting three lenalidomide mol­ecules by hydrogen bonds. The significance of this study lies in the analysis of the inter­actions in these structures and the aggregations occurring via hydrogen bonds in the hydrated and dehydrated crystalline forms of the title compound.

Cisplatin is used frequently as an antineoplastic drug in the treatment of many different cancers. However, when used in doses over 360mg/m², ototoxicity may ensue, resulting in loss of hearing. Criteria for identifying and quantifying hearing loss have been devised. AIM: To describe the features of different hearing loss classification systems and to identify their implications and use in oncologic patients. METHOD: Hearing loss was classified in 31 patients before and after chemotherapy, according to different criteria, assessing the sensitivity and specificity of each classification system. RESULTS: Hearing loss results were highly variable (ranging from 29% to 61%). Only 4 of 31 subjects with post-therapy hearing loss were identified by all the methods. A few subjects with hearing loss were classified as normal hearing in some of the criteria. A normal PTA was found in 18 of 31 subjects in the post-treatment evaluation. CONCLUSION: None of the criteria assesses the complaints of patients. The criteria described in this study were inadequate to identify hearing loss following chemotherapy, requiring additional information for physicians to better understand the hearing losses and their implications for the quality of life of patients. A cisplatina é um antineoplásico muito utilizado no tratamento de diferentes neoplasias, porém quando utilizada em doses acima de 360mg/m² pode causar ototoxicidade. Esta produz lesões cocleares que resultam em perda auditiva. Existem critérios que visam identificar e quantificar as perdas auditivas. OBJETIVO: Descrever as características das classificações e identificar implicações e aplicações de cada uma, dentro das necessidades do acompanhamento ao paciente oncológico. MATERIAL E MÉTODO: Avaliamos 31 pacientes pré e pós-tratamento quimioterápico. Classificamos as perdas auditivas de acordo com os critérios e verificamos a sensibilidade e especificidade de cada um. RESULTADO: Houve grande variabilidade na detecção das alterações auditivas (de 29% a 61%). Somente 4 dos 31 indivíduos com alterações auditivas no exame pós-tratamento foram identificados por todos os critérios. Por vezes o indivíduo portador de perda auditiva era classificado com normal por algum critério. Dos 31 indivíduos, 18 apresentaram PTA normal no exame pós-tratamento. CONCLUSÃO: Nenhum dos critérios considera a queixa do paciente. Os critérios descritos mostraram inadequações para descrever as alterações auditivas encontradas, fazendo-se necessária a descrição de informações adicionais, para que o médico compreendesse a natureza da perda auditiva. É importante o refinamento desses instrumentos para melhor compreensão e tratamento dos pacientes oncológicos, assim como de sua qualidade de vida.

It is a characteristic feature of human cancerous effusions that the cells show great variation and, in particular, it is generally emphasized that therapy does not exert any influence on the chromosomal constitution of the cancer cells. Selection of a cell line during treatment is stated to occur very infrequently. Such a selection of a cell line with a constant number of chromosomes was demonstrated by repeated chromosome analyses in a patient during chemotherapy. The results of the studies are described, and the practical and theoretical aspects are commented upon. – Alterations in the karyotypic profiles in cancerous effusions during treatment with chemotherapeutic agents will require consideration of changing to another agent.

Cisplatin (cis-diamminedicloroplatinum) is an antineoplastic drug used in the treatment of a variety of cancers, especially head-and-neck cancer. Its ototoxicity, however, has been noted as a common side-effect which limits its use and causes significant morbidity. AIM: to assess distortion-product otoacoustic emissions (DPOAE) and brainstem evoked response audiometry (BERA) sensitivity to detect secondary ototoxicity caused by different doses and means of administration of cisplatin in rats. STUDY DESIGN: Experimental. MATERIAL AND METHODS: Male Wistar rats were intraperitoneally (i.p.) injected with 24 mg/kg cisplatin, divided into three equal doses (8mg/kg) or a single i.p. injection of 16 mg/kg. The animals were evaluated by distortion product otoacoustic emission (DPOAE) or brainstem evoked response audiometry (BERA) on the 3rd and 4th days after the cisplatin injection. RESULTS: Treatment with cisplatin 24 mg/kg resulted in significant DPOAE decrease and it raised the BERA electrophysiological threshold. The 16mg/kg dose could not significantly reduce the DPOAE amplitude, but it raised the animals' hearing thresholds - detected by the BERA. CONCLUSION: In rats, BERA was more sensitivity than DPOAE at detecting cisplatin-induced ototoxicity in rats considering different doses and means of administration. Cisplatina (cisdiaminodicloroplatinum) é um agente quimioterápico usado para o tratamento de várias linhagens de neoplasias, mormente as de cabeça e pescoço. Sua ototoxicidade permanece sendo um dos efeitos colaterais causadores de significativa morbidade e limita sua utilização. OBJETIVO: Avaliar a sensibilidade das emissões otoacústicas evocadas produtos de distorção (EOAPD) e potenciais auditivos evocados de tronco encefálico (PAETE) na detecção da ototoxicidade secundária a diferentes doses e formas de administração de cisplatina em ratos. FORMA DE ESTUDO: Experimental. MATERIAL E MÉTODO: Ratos Wistar machos, administrou-se cisplatina por via intraperitoneal (IP) nas doses de 24 mg/kg, fracionada em três doses diárias ou 16 mg/kg em infusão única. Avaliaram-se os animais através de EOAPD ou PAETE no terceiro (D3) e quarto (D4) dias após o início da infusão das drogas. RESULTADOS: O grupo tratado com 24 mg/kg mostrou diminuição significativa da amplitude das EOAPD e aumento do limiar eletrofisiológico pelo PAETE. A dose de 16 mg/kg não foi capaz de promover redução significativa da amplitude das EOAPD, mas elevou o limiar auditivo dos animais, detectado através de PAETE. CONCLUSÃO: Em ratos, os PAETE foram mais sensíveis que as OEAPD na detecção da ototoxicidade por cisplatina para diferentes doses e formas de administração.

Introduction. Antineoplastic drug therapy errors represent a high iatrogenic potential due to antineoplastic drugs narrow therapeutic ranges and the complexity of chemotherapy regimens that may increase the risk of morbidity and mortality for oncology patients.Setting. We report a 57-year-old man with head and neck cancer who mistakenly received 180 mg/ m2of cisplatin overdose despite the safety measures and validations carried out during preparation. The patient developed moderate nausea and vomiting, acute renal failure, hearing difficulty (tinnitus), and severe myelodepression.Patient management. Prophylactic and symptomatic treatments were applied in order to prevent and correct toxicity during the 9 days stay at hospital.Result. He recovered with mild tinnitus and mild renal impairment as the only sequelae. This case presents a hospital stay and treatment quite different to others used to reverse all cisplatin overdose toxicity and it shows the benefits of prompt management.

Hydroxyurea (HU) is an antineoplastic drug widely used in the clinical management of patients with sickle cell disease (SCD), and many questions related with its use remain unresolved. Given the severity of SCD, HU benefits, although not thoroughly confirmed, seem to outweigh its potential carcinogenicity. This study aimed to assess the genotoxicity associated with HU dose and treatment length by evaluating mutagenicity in patients with SCD treated with HU (SCHU) using the cytokinesis-block micronucleus assay (CBMN) in white cells. The study was conducted with 35 individuals in the SCHU group and 34 controls matched according to age, sex and smoking habit. CBMN results showed an increase (p=0.032) in the number of micronuclei (MN), but not of nucleoplasmic bridges (NPB) or nuclear buds (NBUD) in the SCHU group. The increased frequency of MN in the SCHU group was significantly correlated with treatment length and final HU dose, which confirms that patients with SCD treated with HU should be carefully monitored to reduce the risk of carcinogenicity.

Biomarkers (or, more correctly, biological markers) are believed by many to be an integral component of modern antineoplastic drug development ([1][1]). An enhanced molecular understanding of neoplasia, accompanied by more sensitive and higher throughput diagnostic tools, has facilitated an

Among the different families of intracellular molecules that can be modulated during cell damage and repair, mitogen-activated protein kinases (MAPKs) are particularly interesting because they are involved in several intracellular pathways activated by injury and regeneration signals. Despite most of the studies have been performed in non-neurological models, recently a causal role for MAPKs has been postulated in central nervous system disorders. However, also in some peripheral neuropathies, MAPK changes can occur and these modifications might be relevant in the pathogenesis of the damage as well as during regeneration and repair. In this review, the current knowledge on the role of MAPKs in peripheral neuropathies will be discussed.

Nanoscale polymeric micelles have attracted more and more attention as a promising nanocarrier for controlled delivery of antineoplastic drugs. Herein, the doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric four-armed poly(ethylene glycol)-polylactide (PEG-PLA) copolymers were successfully fabricated. In phosphate-buffered saline (PBS) at pH 7.4, SCM/DOX exhibited the smallest hydrodynamic diameter (D h) of 90 ± 4.2 nm and the slowest DOX release compared with PDM/DOX and PLM/DOX. Moreover, PDM/DOX, PLM/DOX, and SCM/DOX exhibited almost stable D hs of around 115, 105, and 90 nm at above normal physiological condition, respectively, which endowed them with great potential in controlled drug delivery. The intracellular DOX fluorescence intensity after the incubation with the laden micelles was different degrees weaker than that incubated with free DOX · HCl within 12 h, probably due to the slow DOX release from micelles. As the incubation time reached to 24 h, all the cells incubated with the laden micelles, especially SCM/DOX, demonstrated a stronger intracellular DOX fluorescence intensity than free DOX · HCl-cultured ones. More importantly, all the DOX-loaded micelles, especially SCM/DOX, exhibited potent antineoplastic efficacy in vitro, excellent serum albumin-tolerance stability, and satisfactory hemocompatibility. These encouraging data indicated that the loading micelles from nonlinear enantiomeric copolymers, especially SCM/DOX, might be promising in clinical systemic chemotherapy through intravenous injection.

Fludarabine (Fludara), a purine nucleoside analogue, is an antineoplastic drug that has been used in the treatment of many lymphoproliferative malignancies, including various types of non-Hodgkin's lymphoma (NHL). I report a patient who has suffered from a severe deterioration in his general condition after receiving Fludara as a single agent for relapsed NHL for which he’s received chemo-immunotherapy.

Objectives: Recently published works showed that occupational exposure to antineoplastic drugs (ANPD) is still frequent in hospital settings, despite significant safety policy improvements. The aim of this study was to assess the current level of occupational exposure to ANPD and any potentially associated cytogenetic damages in hospital nurses routinely handling ANPD. Methods: Occupationally ANPD-exposed (n = 71) and ANPD-unexposed (n = 77; control) nurses were recruited on a voluntary basis from five hospitals in Northern and Central Italy. Evaluation of surface contamination and dermal exposure to ANPD was assessed by determining cyclophosphamide (CP) on selected surfaces (wipes) and on exposed nurses’ clothes (pads). The concentration of unmetabolized CP—as a biomarker of internal dose—was measured in end-shift urine samples. Biomonitoring of genotoxic effects (i.e., biological effect monitoring) was conducted by analyzing micronuclei (MN) and chromosome aberrations (CA) in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e., glutathione S-transferases) were analyzed as well. Results: We observed a significant increase in MN frequency (5.30 ± 2.99 and 3.29 ± 1.97; mean values ± standard deviation; p

Chemotherapy-induced neuropathy is one of the most serious non-life-threatening side effects experienced by patients receiving this group of pharmaceutical agents. Although frequently reversible, some patients may remain with symptoms for the remainder of their lives. Early recognition that "numbness and tingling" in the hands and feet of a patient receiving chemotherapy is due to the antineoplastic drug, with subsequent dose reduction or discontinuation of the offending agent, may prevent the development of serious neurologic dysfunction.

Since the approval of cisplatin as an antineoplastic drug, the medical and the scientific communities have been concerned about the side effects of platinum-based drugs, and this has been the dose-limiting factor that leads to reduced treatment efficiency. Another important issue is the intrinsic or acquired resistance of some patients to treatment. Identifying proper biomarkers is crucial in evaluating the efficiency of a treatment, assisting physicians in determining, at early stages, whether or not the patient presents resistance to the drug, minimizing severe side effects, and allowing them to redirect the established course of chemotherapy. A great effort is being made to identify biomarkers that can be used to predict the outcome of the treatment of cancer patients with platinum-based drugs. In this context, the metallomic approach has not yet been used to its full potential. Since the basis of these drugs is platinum, the monitoring of biomarkers containing this metal should be the natural approach to evaluate treatment progress. This review intends to show where the research in this field stands and points out some gaps that can be filled by metallomics.

Ethidium bromide (EB) is an intercalating inhibitor of topoisomerase II and its activities are related to chemotherapeutic drugs used in anti-cancer treatments. EB promotes several genotoxic effects in exposed cells by stabilising the DNA-enzyme complex. The recombinagenic potential of EB was evaluated in our in vivo study by the loss of heterozygosity of nutritional markers in diploid Aspergillus nidulans cells through Homozygotization Index (HI). A DNA repair mutation, uvsZ and a chromosome duplication DP (II-I) were introduced in the genome of tested cells to obtain a sensitive system for the recombinagenesis detection. EB-treated diploid cells had HI values significantly greater than the control at both concentrations (4.0 x 10-3 and 5.0 x 10-3 mM). Results indicate that the intercalating agent is potentially capable of inducing mitotic crossing-over in diploid A. nidulans cells.

The adsorption of the antineoplastic drug mitomycin C (MC) on the hanging mercury drop electrode (HMDE) surface by means of stripping voltammetry measurements is studied. With this technique, a cat...

Adverse effects similar to those seen in treated cancer patients may occur in healthcare professionals who handle these drugs regularly. The main aim of the study was to explore potential health risks among staff nurses exposed to antineoplastic drugs. The study involved a purposive sample of 150 oncology staff nurses. Data were collected from 5 different hospitals with separate oncology units at Udupi district and Mangalore, Karnataka in India. The data were collected through self-administered potential health risks assessment questionnaire. The results of the study revealed that most of the participants138 (92%) had low degree of potential health risks. Major identified health problems were contact dermatitis (22.7%), nasal sores (12.7%), allergic reaction (16%), hair loss (54%), abortion (3.3%), menstrual problems (18.7%), congenital malformation, behavioral abnormality and intellectual problems in offspring's (1.3%each).

Background The recurrence rate of periocular nodular basal cell carcinoma (PNBCC) following treatment with imiquimod (IMQ) has not yet been established. Previous studies did not include histological follow-up. The aim of this analysis was to evaluate the efficacy of topical immunotherapy with 5% IMQ cream for the treatment of PNBCC. Methods Study design: A prospective, non-randomized, and uncontrolled longitudinal case series study. No participants were blinded. Punch biopsy confirmed PNBCC patients were included at the Ophthalmology Clinic of São Paulo University Medicine School Hospital (from 2008 to 2012). Patients were treated with 5% IMQ cream once a day, 5 days per week, for 8–16 weeks. Standard lesion photographic documentation was done during the study. Three months after treatment ended, an image-guided biopsy was performed. Patients were followed at 6-month intervals and annually for control biopsies. Main outcome measures were clinical and histological clearance rates. Data were analysed by frequency distribution for qualitative group characteristics and central tendency measures for quantitative data. Results Twenty-four patients met the inclusion criteria, 19 of whom remained until the end of treatment. The histological clearance rate was 89.5% and 84.2%, respectively, at 3 and 39.5 months. The 3-year histological clearance rate was 81.8% (9/11) for lesions >10 mm, and 100% (8/8) for lesions 10 mm. Trial registration ClinicalTrial.gov Registration Dec 3, 2008: #NCT 00803907.

Purpose In Japan, biological safety cabinets are commonly used by medical staff to prepare antineoplastic agents. At the Division of Chemotherapy for Outpatients, Nagoya University Hospital, a class II B2 biological safety cabinet is used. The temperature inside this biological safety cabinet decreases in winter. In this study, we investigated the effect of low outside air temperature on the biological safety cabinet temperature, time required to admix antineoplastic agents, and accuracy of epirubicin weight measurement. Methods Studies were conducted from 1 January to 31 March 2008 (winter). The outside air temperature near the biological safety cabinet intake nozzle was compared with the biological safety cabinet temperature. The correlation between the outside air temperature and the biological safety cabinet temperature, time for cyclophosphamide and gemcitabine solubilization, and accuracy of epirubicin weight measurement were investigated at low and high biological safety cabinet temperatures. Result The biological safety cabinet temperature correlated with the outside air temperature of 5–20℃ ( p Conclusion These results suggest that the biological safety cabinet temperature decreases when cool winter air is drawn into the biological safety cabinet, affecting the solubilization of antineoplastic agents. We suggest that a decrease in biological safety cabinet temperature may increase the time required to admix antineoplastic agents, thereby increasing the time for which outpatients must wait for chemotherapy.

Environmental contamination, product contamination and technicians exposure were measured following preparation of iv bags with cyclophosphamide using the robotic system CytoCare. Wipe samples were taken inside CytoCare, in the clean room environment, from vials, and prepared iv bags including ports and analysed for contamination with cyclophosphamide. Contamination with cyclophosphamide was also measured in environmental air and on the technicians hands and gloves used for handling the drugs. Exposure of the technicians to cyclophosphamide was measured by analysis of cyclophosphamide in urine. Contamination with cyclophosphamide was mainly observed inside CytoCare, before preparation, after preparation and after daily routine cleaning. Contamination outside CytoCare was incidentally found. All vials with reconstituted cyclophosphamide entering CytoCare were contaminated on the outside but vials with powdered cyclophosphamide were not contaminated on the outside. Contaminated bags entering CytoCare were also contaminated after preparation but non-contaminated bags were not contaminated after preparation. Cyclophosphamide was detected on the ports of all prepared bags. Almost all outer pairs of gloves used for preparation and daily routine cleaning were contaminated with cyclophosphamide. Cyclophosphamide was not found on the inner pairs of gloves and on the hands of the technicians. Cyclophosphamide was not detected in the stationary and personal air samples and in the urine samples of the technicians. CytoCare enables the preparation of cyclophosphamide with low levels of environmental contamination and product contamination and no measurable exposure of the technicians.

Purpose In a follow-up to a previous study, surface contamination with the antineoplastic drug cyclophosphamide was compared in 30 US hospital pharmacies from 2004 to 2010 following preparation with standard drug preparation techniques or the PhaSeal closed system drug transfer device (CSTD). Methods Wipe samples were taken from biological safety cabinet (BSC) surfaces, BSC airfoils (the front leading edge of the BSC), floors in front of BSCs, and countertops in the pharmacy, and they were analyzed for contamination with cyclophosphamide. Contamination was reassessed after a minimum of 6 months following the implementation of the CSTD. Surface contamination (ng/cm2) was compared between the 2 techniques and between the previous and current test periods and evaluated with the Kruskal-Wallis test. Results With the use of CSTD compared to the standard preparation techniques, a significant reduction in levels of contamination with cyclophosphamide was observed ( P < .0001). Median values for surface contamination with cyclophosphamide were reduced by 86% compared to 95% in the previous study. Conclusions The CSTD significantly reduced, but did not totally eliminate, surface contamination with cyclophosphamide. In addition to other protective measures, increased usage of CSTDs should be employed to help protect health care workers from exposure to hazardous drugs.

In the current study a facile synthetic route for preparing antineoplastic drug GDC-0449 is investigated. Starting with pyridine-1-oxide and 1-iodo-3-nitrobenzene, the intermediate product 2-(2-chloro-5-nitrophenyl) pyridine was prepared by cross-coupling, deoxidation and halogenation. The final compound was then synthesised by reduction of the nitro group followed by amidation. This synthetic route avoids the use of unstable organometallic or organic boride compounds; it employs relatively inexpensive and bench-stable reagents, involves readily controllable reaction conditions, and achieves a relatively high yield.

A bleomicina é agente quimioterápico usado no tratamento de diferentes neoplasias. Apresenta vários efeitos colaterais, sendo um deles a hiperpigmentação cutânea de aspecto flagelado, considerada específica dessa droga. Relatam-se dois casos de dermatite flagelada induzida pela bleomicina. Discutem-se os aspectos clínicos e etiopatogênicos em breve revisão bibliográfica. Bleomycin is an antineoplastic drug used in the treatment of different tumors. It has several side effects, including a cutaneous hyperpigmentation with a flagellate aspect, which is considered specific to Bleomycin. We report two cases of Bleomycin-induced flagellate dermatitis and discuss the clinical and etiopathogenic aspects in a brief blibliographic revision.

Tegafur (TGF) is an antineoplastic drug which used for treatment of neoplasm of gastro-intestinal tract including colon cancer. Cellulose acetate butyrate microspheres containing the drug were prepared by using the emulsion-solvent evaporation technique. The microspheres were spherical and free flowing. The yield was greater than 97% and more than 95% of the drug was encapsulated. The effect of microsphere size and pH of the dissolution medium on the drug release was investigated. Sustained release profiles of TGF from TGF-CAB microspheres were observed. In all cases the drug release followed Higuchi diffusion model. Microspheres of smaller size gave a relatively higher dissolution rate of the drug. The drug release was slower in acidic medium (pH 1.2) suggesting that using CAB microspheres would be of value for controlling the drug release and potential colonic-targeting of the drug.

The kinetics of an antineoplastic drug, suramin, described by a three-compartment, open, linear model is studied in this report. A population pharmacokinetic model, describing the pharmacokinetics of suramin, was developed using the iterative-two stage approach, with maximum a posteriori-Bayesian priors. It was further validated using data from a subsequent study (validation data set). The population pharmacokinetic parameters were also estimated by generating bootstrap samples from the validation data set. When the prior distribution was close to the population distribution, there was no significant difference between the estimates obtained using the iterative-two stage approach and the bootstrap approach. However, when estimating population pharmacokinetic parameters, the iterative-two stage approach was less sensitive to prior distribution specification

Made available in DSpace on 2014-12-03T13:11:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-01-01Bitstream added on 2014-12-03T13:22:50Z : No. of bitstreams: 1 WOS000331608000193.pdf: 317025 bytes, checksum: aee30c8baf1d6d815e4ee039e14ea833 (MD5) Pro-Reitoria de Pesquisa e Pos-Graduacao - Centro Universitario Filadelfia (UniFil) Fundacao Araucaria: Apoio ao Desenvolvimento Cientifico e Tecnologico do Parana Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia (FUNDECT) of the State of Mato Grosso do Sul Cisplatin is an effective antineoplastic drug. However, it provokes considerable collateral effects, including genotoxic and clastogenic activity. It has been reported that a diet rich in glutamine can help inhibit such collateral effects. We evaluated this activity in 40 Swiss mice, distributed into eight experimental groups: G1 - Control group (PBS 0.1 mL/10g body weight); G2 - cisplatin group (cisplatin 6 mg/kg intraperitoneally); G3, G4, G5 - glutamine groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally); G6, G7, G8 - Pre-treatment groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally and cisplatin 6 mg/kg intraperitonially). For the micronucleus assay, samples of blood were collected (before the first use of the drugs at T0, then 24 (T1) and 48 (T2) hours after the first administration). For the comet assay, blood samples were collected only at T2. The damage reduction percentages for the micronucleus assay were 90.0, 47.3, and 37.3% at T1 and 46.0, 38.6, and 34.7% at T2, for G6, G7, and G8 groups, respectively. For the comet assay, the damage reduction percentages were 113.0, 117.4, and 115.0% for G6, G7, and G8, respectively. We conclude that glutamine is able to prevent genotoxic and clastogenic damages caused by cisplatin. Univ Fed Mato Grosso do Sul, Nucleo Hosp Univ, Ctr Estudos Celulas Tronco Terapia Celular & Gene, Campo Grande, MS, Brazil Univ Fed Mato Grosso do Sul, Fac Med Dr Helio Mandetta, Programa Posgrad Saude Desenvolvimento Regiao Ctr, Campo Grande, MS, Brazil Univ Fed Mato Grosso do Sul, Ctr Ciencias Biol & Saude, Programa Mestrado Farm, Campo Grande, MS, Brazil Ctr Univ Filadelfia, Ctr Estudo Nutr & Genet Toxicol CENUGEN, Londrina, PR, Brazil Univ Fed Mato Grosso do Sul, Ctr Ciencias Biol & Saude, Campo Grande, MS, Brazil Univ Estadual Paulista, Programa Posgrad Biol Celular & Mol, Inst Biociencias, Rio Claro, SP, Brazil Univ Estadual Londrina, Dept Biol Geral, Londrina, PR, Brazil Univ Estadual Paulista, Programa Posgrad Biol Celular & Mol, Inst Biociencias, Rio Claro, SP, Brazil

We analyzed the errors occurring in the preparation circuit of cytotoxic mixtures of the Centralized Cytotoxic Preparation Unit during one year. Analysis of their evolution meant the investigation of twenty parameters susceptible to error. Each parameter was considered one error opportunity. Error has been defined either by the lack of data or mistake in the controlled parameter. In 4,734 preparations (94,680 parameters) there were 314 errors. The percentage of error per parameter in the first month of study was 0.74; at sixth was 0.34 and the last month was 0.26. Only in four months the day of maximum number of preparations coincided with the day of maximum number of errors. We conclude that the percentage of errors in the preparation process is low with a tendency to decrease and that the number of daily preparations is not the single factor that influences the production of errors.

The antineoplastic drug etoposide has been prepared by a chemically and operationally simple process. The salient reaction is the BF3 etherate promoted, room temperature condensation of 4′-demethyl-4′-acetyl-epipodophyllotoxin 4, with α-1-Bu3Sn-O-2,3-bisacetyl-4,6-ethylidene-glucose 6. The latter compound was prepared from 4,6-β-ethylidene glucose triacetate and Bu3Sn-OMe obtained in situ from (Bu3Sn)2O and dimethyl carbonate. A readily separable mixture of α and β-etoposide triacetate epimers was obtained where the desired β-epimer predominated. In contrast, 4,6-α-ethylidene glucose diacetate and 4, even at 0°C, gave an equimolar mixture of epimers. It is proposed that the stereochemical outcome may be attributed to electronic effects in the activated tin-glucose reagent.

Despite the fact that research in the mechanism of vomiting goes back more than 300 years, there are still major gaps in our knowledge. The first report of the clinical use of an antineoplastic drug was published in 1942, but it was not until cisplatin, the most emetogenic of all drugs, was approved in 1978, the necessity of focusing on antiemetic research became evident.

A large-scale study was carried out in order to determine the contamination level of antineoplastic drugs in pharmacies and to investigate the suitability and effects of wipe sample monitoring at regular intervals. A specific study design was developed. The 130 participating pharmacies were divided into a study and a control group, carrying out five and two wipe sampling cycles, respectively. The work practice was analyzed using questionnaires to identify factors that influence the contamination level. From 1269 wipe samples, 774 (61%) were contaminated with at least one of the analyzed cytotoxic drugs: cyclophosphamide, docetaxel, etoposide, 5-fluorouracil, gemcitabine, ifosfamide, methotrexate, and paclitaxel. A significant decrease of the contamination with cyclophosphamide and 5-fluorouracil was observed in the study group. The Monitoring-Effect Study of Wipe Sampling in Pharmacies method has proven to be a reliable and affordable tool for contamination control. Based on the 90th percentile of the contamination values, a substance-independent performance-based guidance value of 0.1ng cm(-2) has been derived.

A treatment algorithm and preprinted order form developed to reduce the cost of treating antineoplastic drug-induced nausea and vomiting are described. A team including pharmacists, oncologists, and oncology nurses developed a treatment algorithm to reduce the cost of antiemetic therapy for patients receiving antineoplastic therapy at a 719-bed academic medical center. The algorithm incorporated the following concepts: matching antiemetic therapy with the emetogenic potential of the antineoplastic regimen, reducing ondansetron dosages, increasing the ratio of oral to intravenous therapy, and treating delayed-onset nausea and vomiting without using serotonin-receptor antagonists. To help physicians learn and use the treatment algorithm, it was incorporated into an order form for both antineoplastic and antiemetic drugs. Separate order forms were created for pediatric and adult patients. A comparison of outcome data before and after implementation of the practice guidelines showed that the patient outcomes were at least as good after implementation as before. More than a year after the guidelines were implemented, more than 85% of antiemetic regimens prescribed for antineoplastic drug-induced nausea and vomiting were in compliance with the guidelines. A cost avoidance of nearly $205,000 was realized in the first year. Collaboration with oncologists at the start of the care plan was a key element in its success. An antiemetic treatment algorithm, integrated with a preprinted physician order form, was well accepted and has reduced expenses for antiemetic therapy.

A chemical-shift selective (CHESS) 19 F MR imaging technique was used to map selectively the antineoplastic drug 5-fluorouracil (5-FU) and its major catabolite α-fluoro-β-alanine (FBAL) in tumor-bearing rats. The pulse sequence employed a CHESS RF saturation pulse to suppress either the 5-FU or the FBAL resonance before the other component in the two-line 19 F MR spectra was measured. Selective 5-FU and FBAL images with a spatial resolution of 10 x 10 x 15 mm 3 (1.5 ml) were obtained in 40 min from six ACI rats with implanted Morris hepatoma. Because the transmitter frequency could always be set to the Larmor frequency of the 19 F resonance employed for imaging, the images were free of chemical-shift artifacts in readout and slice-selection direction. Whereas FBAL appeared only in the liver, the kidneys, and the bladder, 5-FU could also be detected in all major organs and in the muscular system. In the Morris hepatomas, a small 5-FU uptake and no FBAL accumulation were measured. The CHESS 19 F MRI technique provides useful physiological and biochemical data on the biodistribution of the antineoplastic drug 5-FU and on the different catabolic activities of the tissues.

(1995). Design and Formulation of Tablets of a New Antineoplastic Drug: Amonafide. Drug Development and Industrial Pharmacy: Vol. 21, No. 2, pp. 185-197.

Introduction Vincristine is an antineoplastic drug with a well known efficacy for the treatment of acute lymphoblastic leukemia and many solid tumors. No more than 20 pediatric patients with vincristine-induced vocal cord palsy have been reported, and to the best of our knowledge this is the first case where glutamic acid was administered with the aim of preventing a relapse of laryngeal dysfunction. Case presentation The larynx paralysis presented with hoarseness and stridor in a Caucasian 18-month-old girl and spontaneously resolved in about a month. In order to administer a subsequent full dose of vincristine, our patient received oral glutamic acid whose efficacy against vincristine neurological side effects has been previously reported. Conclusions Since in our patient the amino acid proved to be ineffective in the prevention of laryngeal paralysis relapse, we suggest that a dose reduction of vincristine should be preferred by oncologists as an initial approach after a case of drug-induced vocal cord palsy.

Cinnamic acid derivatives can be found in plant material, and they possess a remarkable variety of biological effects. In the present study, we have investigated the cytotoxic effects of representative cinnamic acid esters and amides. The cytotoxicity was determined by MTT test on human cervix adenocarcinoma (HeLa), myelogenous leukemia (K562), malignant melanoma (Fem-x), and estrogen-receptor-positive breast cancer (MCF-7) cells, versus peripheral blood mononuclear cells (PBMCs) without or with the addition of the plant lectin phytohemaglutinin (PHA). The compounds tested showed significant cytotoxicity (IC(50)s between 42 and 166 mu M) and furthermore selectivity of these cytotoxic effects on the malignant cell lines versus the PBMCs was also seen, especially when electron-withdrawing groups, such as a cyano group (compound 5), were present on the aromatic rings of the alcohol or amine parts of the cinnamic acid derivatives. The additional study on cell cycle phase distribution indicated that novel cinnamic acid derivatives inhibit cell growth by induction of cell death. Thus, cinnamic acids derivatives represent important lead compounds for further development of antineoplastic agents.

The chemical and pharmaceutical industry is under an accelerating pressure to find environmentally friendly organic reaction methodologies. Owing to the unique advantages of ionic liquids, the preparation and industrial applications of ionic liquids have attracted considerable interest. Herein we report novel synthesis of imidazolium based Room-Temperature Ionic Liquid (RTIL) using cheaper reagents which have been used for the synthesis of Antiandrogenic and Antineoplastic drug Bicalutamide and its impurities reported in US pharmacopoeia.

Molti dei farmaci antineoplastici utilizzati nelle terapie oncologiche mostrano cancerogenicità, mutagenicità o teratogenicità verso l'uomo. Dal momento che la gran parte dei citostatici non presenta un meccanismo di azione selettivo nei confronti delle sole cellule tumorali, il loro utilizzo è correlato all'insorgenza di tumori primari nei lavoratori preposti alla loro manipolazione, rischio professionale che va tutelato. Uno strumento imprescindibile per la riduzione del rischio di assorbimento dei chemioterapici antiblastici in ambito lavorativo è rappresentato dal Monitoraggio Ambientale, in grado di delineare in maniera puntuale il livello d'inquinamento presente nei locali preposti alla manipolazione/somministrazioneai pazienti dei preparati, ma anche di mettere in luce carenze organizzativo/strutturali critiche ai fini dell'abbattimento/riduzione dell'inquinamento. Il presente lavoro illustra i risultati di diverse campagne di Monitoraggio Ambientale condotte tra il 2004 ed il 2008 in ospedali dell’area campana. Gli analiti, scelti in base alla loro tossicità intrinseca e alla percentuale di utilizzo nelle terapie, erano ciclofosfamide (CP), ifosfamide (IF), 5-fluoruracile (5FU), doxorubicina (DOXO) ed epirubicina (EPI). Il monitoraggio ambientale è stato effettuato mediante tecnica del wipe-test; gli analiti sono stati purificati ed analizzati mediante metodi pienamente validati in accordo con le linee guida della FDA. In tutti i reparti oncologici esaminati è stata evidenziata una non aderenza alle indicazioni delle linee guida relative alla manipolazione dei chemioterapici antiblastici. Il grado di contaminazione riscontrato risultava 1000 volte superiore rispetto ai valori riportati nella letteratura internazionale. I dati suggeriscono una non adeguatezza delle modalità di lavoro e delle procedure di pulizia, evidenziando la necessità di procedere con campagne d’informazione/formazione degli addetti alla manipolazione, al fine di renderli pienamente consapevoli dei rischi connessi all’attività lavorativa. Appare, inoltre, di primaria importanza la pianificazione di campagne di monitoraggio su base annuale, quale strumento imprescindibile per verificare l’efficacia delle strategie di risk management adottate per diminuire i livelli di esposizione a chemioterapici antiblastici Background. Many antineoplastic drugs (AD) commonly used in therapies display cytotoxic activity and are classified as potentially carcinogen, mutagen or teratogen. Since antineoplastic drugs are not selective towards malignant cells, their use may derive in the development of primary tumours in healthy subjects occupationally exposed to such agents, an occupational risk against which workers must be defended. The Environmental Monitoring represents a valid instrument in risk reduction strategies, since it allows the definition of the pollution levels actually present in the whole working areas and at the same time it can point out eventual structural and/or organizational lacks to be improved for pollution reduction. Aim of the study. The present work reports results of Environmental Monitoring campaigns performed between 2004 and 2008 in oncology wards of different hospitals located in Campania area. Analytes were chosen considering both their intrinsic toxicity properties and the amount handled for therapies. In particular, cyclophosphamide (CP), ifosfamide (IF), 5-floruracil (5FU), doxorubicin (DOXO) and epirubicin (EPI) were considered. Methods. Environmental Monitoring was performed by wipe-test sampling of potentially contaminated surfaces, analytes purification and GC/MSMS (CP, IF), HPLC/UV (5FU) or HPLC/FL (DOXO, EPI) analysis. Analytical methods used were fully validated according to the Food and Drug Administration Guidelines. The descriptive analysis (concentration ranges, median or mean, dispersion indices etc.) was performed to give a global image of the pollution situation of the examined drug preparation rooms. Inferential analyses were applied to evaluate the correctness of working and cleaning modalities, i.e. the effectiveness of formation/information training courses, as well as the actual application of national/international directives about antineoplastic drugs handling. Results. In all examined oncology wards several discrepancies between actual working modalities/organization and Italian Guidelines for AD manipulation have been evidenced. Pollution levels found for the considered analytes varied in a wide concentration ranges, being almost 1000 times greater with respect to data reported in the international literature (µg dm-2 vs. ng dm-2). A diffuse contamination throughout the drug preparation rooms was found and analytes were found, even if in traces, in days when they were not used at all. Conclusions. Obtained data suggest the non-adequacy of both working modalities and cleaning procedures adopted, thus evidencing the need of new formation/information training courses for nurses devoted to AD manipulation. In fact, nurses of almost all examined wards seemed to be not consciousness of the risks related to their job activities. Results further highlighted the crucial role played by Environmental Monitoring campaigns, as unique tool for verifying the effectiveness of risk management strategies adopted for AD exposure reduction.

The pharmaceutical development of tablets of a 1,8 naphtalimide with antineoplastic activity is carried out in two steps. The preformulation step includes the study of those characteristics of the drug with special importance for the successful development of the formulation step. In this way, the low moisture, the low porosity and the good flowability of the drug as raw material allow direct compression to be taken into account, together with wet granulation as methods of tablet manufacture. As a result of the formulation studies, one formulation of tablets obtained by direct compression and another one obtained by wet granulation are selected. Both of them meet all the requirements imposed to a solid pharmaceutical form for oral administration.

A formal training program for technicians who prepare cytotoxic agents and pharmacists who check the doses is described. To handle an overwhelming workload in an oncology satellite pharmacy and to enable the pharmacists there to increase their clinical involvement, a program was developed to train technicians to prepare antineoplastic doses and pharmacists to check the technicians' work. The program consists of two days of classroom instruction, three weeks of hands-on training, and a written examination. In addition to handling and preparation of antineoplastic drugs, other topics related to oncology are covered to give the participants a better understanding of cancer and its treatment. The technicians must complete a refresher program annually. From 1991 to 1993, 15 pharmacists and 14 technicians and pharmacy students completed the program. The technicians have taken on additional responsibilities in the satellite pharmacy, including managing the inventory of oncology drugs. Implementation of a comprehensive cancer chemotherapy training class for technicians and pharmacists has benefited the pharmacy in terms of labor and inventory control.

Water and wastewater effluents contain a vast range of pharmaceutical chemicals. The present study aims to determine the potential of the advanced oxidation technology UV/H 2 O 2 /O 3 and its sub-processes (i.e. UV, UV/H 2 O 2 , UV/O 3 , O 3 and H 2 O 2 /O 3 ) for the degradation of the antibiotics ciprofloxacin (CIP) and trimethoprim (TMP), and the antineoplastic drug cyclophosphamide (CPD) from water. Creating AOP conditions improved in most cases the degradation rate of the target compounds (compared with O 3 and UV alone). H 2 O 2 concentration was found to be an important parameter in the UV/H 2 O 2 and H 2 O 2 /O 3 sub-processes, acting as • OH initiator as well as • OH scavenger. Out of the examined processes, O 3 had the highest degradation rate for TMP and H 2 O 2 /O 3 showed highest degradation rate for CIP and CPD. The electrical energy consumption for both CIP and CPD, as calculated using the E EO parameter, was in the following order: UV > UV/O 3 > UV/H 2 O 2 /O 3 > O 3 > H 2 O 2 /O 3 . Whereas for TMP O 3 was shown to be the most electrical energy efficient. Twelve degradation byproducts were identified following direct UV photolysis of CIP.