Nitrofurantoin

By F. Stan. University of Maine. 2018.

Placebo-controlled trials of mitoxantrone Trial Patient characteristics Mitoxantrone dose Comparator Study duration RRMS or SPMS Edan order nitrofurantoin 50 mg overnight delivery bacteria helicobacter pylori sintomas, 94 Mean baseline EDSS: 4 buy nitrofurantoin 50 mg otc infection in lymph nodes. The study authors determined that the dose was too difficult to compare to the dosing schedules employed in the other studies. Effectiveness outcomes in trials of mitoxantrone compared with 92 placebo Outcome Time point Number Results a 68. Disease-modifying drugs for multiple sclerosis Page 45 of 120 Final Report Update 1 Drug Effectiveness Review Project Mixed populations: Primary and secondary progressive multiple sclerosis Glatiramer acetate ® An early, good-quality study of glatiramer acetate (Copaxone ) was conducted in a population of 106 patients described as chronic progressive (a chronic progressive course for at least 18 months, no more than 2 exacerbations in the past 2 years, Expanded Disability Status Scale ≥2 97 and ≤6. Many clinicians consider this group of patients to represent a mix of patients with what would now be called primary or secondary progressive multiple sclerosis. The drug used in this study was available from 2 laboratories in Israel and was not the commercially available glatiramer acetate (known as COP-1 at the time). The dosing of the drug was 15 mg subcutaneously twice daily, a dose that is higher than currently used (20 mg subcutaneously daily). The mean baseline Expanded Disability Status Scale was slightly higher in the glatiramer acetate group (5. Comparing time to sustained progression curves (the primary outcome) while the glatiramer acetate curve showed slower progression, no significant difference was found between the groups over a 2-year period. This study did not conduct a sample size calculation, and with 106 patients may have been underpowered to show a difference of this magnitude. Further, subgroup analyses indicated that patients enrolled at the 2 centers responded differently while on study, and that overall patient disease activity differed on trial compared with the pre-trial assessment period. Analysis of secondary outcomes indicated that statistically significant differences in proportions with progression (defined as an increase on Expanded Disability Status Scale of ≥ 1 if baseline ≥ 5, and 1. The authors also explored a definition of progression of an increase of only 0. Using this definition, the probability of progression was significantly lower with glatiramer acetate compared with placebo only at the 24-month time point (44. Do disease-modifying treatments for multiple sclerosis differ in their effects on the development or recurrence of interferon beta neutralizing antibodies? Summary of the Evidence ® • Interferon beta-1a IM (Avonex ) appeared to have the lowest immunogenicity, with rates of development of neutralizing antibodies of 2% to 8. Disease-modifying drugs for multiple sclerosis Page 46 of 120 Final Report Update 1 Drug Effectiveness Review Project Detailed Assessment Neutralizing antibodies are known to develop in some patients taking beta interferons, potentially interfering with effectiveness. Two systematic reviews summarized the current state of understanding about the impact 98, 99 of these antibodies on relapse and disease progression, and how the products differ. There were several factors that can impact the prevalence of such antibodies, including assay method (varying sensitivity/specificity), dose (conflicting evidence), host cell source (Escherichia coli more antigenic than mammalian source), definition of positive status, and route of administration (subcutaneous more antigenic than intramuscular). Because there is no standardized universal assay, comparisons across studies of the beta interferons is fraught with uncertainty. It appears that the rate of antibody development occurs earlier and in greater frequency with interferon ® beta-1b SC (Betaseron ), appearing as early as 3 months into treatment in approximately 30% to 99 40% of patients. Evidence reported in the Namaka review indicated that antibodies occur ® somewhat later (9 months) with interferon beta-1a SC (Rebif ), with rates as low as 12% and as ® high as 46% (see Table 18). Interferon beta-1a IM (Avonex ) appeared to have the lowest immunogenicity with rates of 2% to 8. Importantly, 40% to 50% of antibody-positive patients will become antibody-negative over time, while small numbers of patients will become antibody-positive into the second year of treatment. Comparison of neutralizing antibodies in beta interferon products Avonex Betaseron Rebif Percent developing neutralizing 2% to 6% 30% to 40% 12% to 25% antibodies First 3-6 months, can Time to appear First 9-15 months First 9-15 months occur up to month 18 Data from 9 comparative observational studies reporting the presence of neutralizing 100-108 antibodies in patients taking beta interferons are shown in Table 19 below. The proportion ® of patients developing antibodies was lower for interferon beta-1a IM (Avonex ), 0% to 14%, ® compared with 11% to 44% with interferon beta-1a SC (Rebif ) and 15% to 44% with interferon ® beta-1b SC (Betaseron ), consistent with findings from the Namaka systematic review. The usefulness of these studies in making comparisons across drugs was limited because most did not study patients on therapy for more than 2 years. Disease-modifying drugs for multiple sclerosis Page 47 of 120 Final Report Update 1 Drug Effectiveness Review Project Table 19. Proportion of patients testing neutralizing antibody-positive after beta interferon therapy reported in comparative observational studies Association of clinical Author, Duration of outcomes with neutralizing ® ® ® year treatment Avonex Betaseron Rebif antibody status More relapses in neutralizing 16/131 Boz, 2007 >3 years 0/12 (0%) 18/119 (15%) antibody-positive patients in (12. Relapse rates higher in Farrell, 24/292 neutralizing antibody-positive >3 years 4/242 (6%) 11/115 (28%) 2008 (30%) groups, risk greater in those with higher titres Median 26 No significant association Dubois, 10/23 months, range 0/18 (0%) 12/32 (38%) between antibody status and 2006 (44%) 2-85 months outcomes. Kivisakk, No effect of neutralizing 1-46 months 1/20 (5%) 21/48 (44%) 2000 antibodies on clinical outcome Koch- 21,963 Effect of neutralizing antibody N=417 N=892 Henriksen months of status on relapses did not differ 33.

Any drug therapy in pregnancy should way connector (Y-connector) 50 mg nitrofurantoin mastercard antibiotic resistance vets. To administer a be avoided if possible and should be given accord- second drug without the risk of an interaction buy nitrofurantoin 50 mg otc virus 5 cap, stop ingly only after establishing a strict indication for the infusion, rinse the connection with normal the therapy. Adverse effects can be caused by a 460 Management of Low-cost Drugs and Equipment direct effect on the fetus after crossing the placental Prescribing drugs in pregnancy barrier or they can occur in relation to physio- • Establish the need for drug therapy: is there an logical changes in the mother’s body. The follow- urgent indication for the treatment of the ing distinctions are made: mother? Do the benefits for the mother out- • Genotoxic drugs: these drugs affect embryonic weigh a potential risk for the fetus? However, the drug therapy the second and third trimester. CYP450 is a group of may have to be adapted, for example if possible key enzymes for the elimination of many drugs. Overview of effects of drugs in pregnancy and lactation What to do in cases of suspected exposure to a teratogenic drug • Drugs affecting the female reproductive system. Second establish as clearly as possible the time of • Drugs affecting labor. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer alternatives cannot be used or are ineffective X Adequate well-controlled or observational studies in animals or pregnant women have demonstrated a positive evidence of fetal abnormalities or risks. The use of the drug is contraindicated in women who are or may become pregnant. Do not use in 3rd products drugs trimester of pregnancy Analgesics Paracetamol Aminoglycoside Fetal toxicity Anti-histaminic Diphenhydramine, dimenhydrinate, antibiotics drugs clemastine Chloramphenicol Grey syndrome Antibiotics Penicillins, cephalosporins, clinda- Tetracyclines Affect bones and teeth mycin, erythromycin Carbamazepine Increased risk for spina bifida Anti-asthmatic Beta2-sympathomimetics drugs (e. If using a drug with known adverse effects on the infant is unavoidable, consider interrupting breastfeeding for the period of medication: show the mother risks for the fetus, i. Further action will depend on a thorough risk evaluation. The risk SAFE HANDLING OF CYTOTOXIC DRUGS level of drugs in pregnancy is commonly indicated using the system shown in Table 2. Examples of This section aims at providing some key elements drugs with established toxic effects for the embryo to ensure safe handling of cytotoxic drugs but or fetus are shown in Table 3 and drugs that can cannot replace the need for further guidance. It will be considered for use in pregnancy are listed in focus in particular on measures that can be used in Table 4. In order the drug preparation to be administered and on the to achieve suitable protection use of double- different steps of preparation and administration. Both pairs of gloves must products needs to be taken into account as well. The risk is highest for the preparation and adminis- • Eye protection: personnel should wear well- tration of injectable preparations because direct ex- fitting glasses for the preparation of cytotoxic posure is more likely, e. Special safety other activities such as dividing or crushing tablets equipment exists but is not widely available in result in high exposure as well. In the absence of such sure, keep in mind that patients’ excretions may equipment, surgical masks can be used as an contain unchanged cytotoxic drugs or active alternative to achieve a reasonable level of pro- metabolites as well. However, surgical masks do not provide In specialized hospitals and better-resourced complete protection against aerosols. Personnel should be knowledge- All preparations should be done in a designated able about the risks and must be trained for the safe room, separate from handling of other drugs and handling of these products. It is good practice to limit access to this room to trained personnel only. The room should have a sufficiently big working area and a Personnel washing facility. Beside medical staff, personnel to be items that are needed for the preparation are trained may also include, for example, cleaners. All procedures should be displayed in tion step by step. It is good prac- tice to use labels that clearly identify the product Personal protection measures as a cytotoxic drug.

Unlicensed NK in vivo suppression by CD4( )CD25( )Foxp3( ) regulatory cells target neuroblastoma following anti-GD2 antibody treat- T cells nitrofurantoin 50 mg with amex infection under tooth. Recognition of presentation promotes human NK cell development and differ- the nonclassical MHC class I molecule H2-M3 by the receptor entiation in vivo 50 mg nitrofurantoin visa treatment for dogs broken leg. Ly49A regulates the licensing and activation of NK cells. NKp46 is the major co-express major histocompatibility complex class I chain- triggering receptor involved in the natural cytotoxicity of fresh related protein A, 4-1BB ligand, and interleukin-15. Miller JS, Soignier Y, Panoskaltsis-Mortari A, et al. Contact- therapy with cytokine-induced killer cells for patients with dependent stimulation and inhibition of dendritic cells by relapsed hematologic malignancies after allogeneic hematopoi- natural killer cells. Up-regulation of a death activated natural killer cells after allogeneic bone marrow receptor renders antiviral T cells susceptible to NK cell- transplantation. Noone CM, Paget E, Lewis EA, Loetscher MR, Newman RW, make a natural killer? Dave1 1Department of Medicine, Duke University School of Medicine, Durham, NC The application of high-throughput genomic approaches in lymphomas has generated a wealth of data regarding the molecular underpinnings of these cancers. In this review, key findings from recent studies are discussed, as well as the genetic heterogeneity that underlies common lymphomas including diffuse large B-cell lymphoma, Burkitt lymphoma, and chronic lymphocytic leukemia, and the implications for identifying new therapeutic opportunities and personalized medicine. Introduction proposed, being used in several clinical trials and offering a simple Lymphomas represent a diverse group of malignancies comprising method for risk stratification of patients with the worst prognosis. However, even within an individual diagnosis, there is usually considerable Molecular approaches using gene expression profiling to subgroup heterogeneity2 with respect to clinical outcome, genetic alterations, DLBCLs have added considerably to our understanding of the and the expression of commonly assayed markers. For example, several gene expression discerning the correct diagnosis and prognosis for an individual profiling studies of patients with DLBCL demonstrated that the patient with lymphoma remains a daunting clinical challenge. One subgroup, new opportunities for understanding the molecular building blocks termed germinal center B-cell-like (GCB) DLBCL, shares character- of cancers. The 2 main tools of these technologies, microarrays and istics of normal germinal center B cells, including the expression of high-throughput sequencing, have led to a sea change in our genes such as BCL6 and CD10. The other subgroup, termed approach to tumor-based measurements. Rather than individual activated B-cell-like (ABC) DLBCL, expresses genes associated measurements of gene expression or genetic alteration, it is now with B-cell activation, including Pim-1 kinase and IRF4. Five-year possible to simultaneously assay these in a genome-wide fashion survival rates for patients with ABC and GCB are significantly using genomics technologies. The application of these powerful different, with a rate of nearly 75% for GCB patients but less than technologies has yielded several insights into the molecular pro- 30% for those with ABC DLBCL. Other approaches to subgrouping DLBCL using gene expression Although it is not practical to describe the findings in every profiling have also been proposed. In particular, another scheme lymphoma type in sufficient detail, we describe the application of uses gene expression profiling to identify 3 distinct subgroups of genomics in 3 separate lymphoid tumors, diffuse large B-cell DLBCL including those related to B-cell receptor (BCR) activation, lymphoma (DLBCL), Burkitt lymphoma (BL), and chronic lympho- host response, and oxidative phosphorylation. However, the biological mechanisms and genomic majority of the patients who fail to respond will succumb to the alterations that are responsible for these changes in gene expression disease. It has proved difficult to develop new therapies for patients are still poorly understood. An important reason for the failure of many clinical signatures have been derived from single studies using microarray- trials in DLBCL may be the approach to the disease as a single based gene expression. Evaluating and extending these signatures in entity, even though it is known to be molecularly and clinically RNA-sequencing-based gene expression measurements could illu- heterogeneous. The most widely adopted clinical risk stratification of DLBCL remains the International Prognostic Index (IPI),5 a multivariate Parallel efforts have attempted to integrate outcome associated gene score composed of age, stage, performance status, serum LDH, and expression into clinically useful prognostic panels with some extranodal disease sites. In particular, an assay based upon quantitative PCR of 6 standard for clinical stratification nearly 2 decades after it was genes (LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2)12 that Hematology 2013 331 Table 1. Summary of clinically relevant and molecular features of common lymphomas Common genetic aberrations Other useful clinical markers DLBCL Mutations in MLL2, MLL3, TP53, BCL6, SETD2, SGK1, MYD88, IPI is highly associated with survival. BL Translocation of MYC, mutations in ID3, TP53, GNA13, IPI is also predictive in BL.

C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating R esults Data givenas ond vs gran Com pleteresponse:acute:nonauseaandnovom iting discount nitrofurantoin 50mg with mastercard antibiotics enterococcus,andnonausea+novom iting N onausea:acute:72 discount nitrofurantoin 50mg on line antibiotic resistance data. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating A dverse events C om m ents 15m inafterstudydrug adm inistrationfinished,cisplatininfusionbeganand wasgivenover30m in. Theotherchem oagentsweregivenim m ediately aftertheendof thecisplatininfusion. G ranandO ndgiventopatientsonday1only;soday1wasthe DelF avero weakness:2. G ran:1ptdiedduring first24hours; 2ptsfailedtoreceiveantiem etic therapyafterrandom iz ation;1ptwaslostto Antiemetics Page 38 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear A ge Setting A llow oth er G ender H esketh rating Design Subpopulation Intervention m edication R un-in/W ash -out Eth nicity Yes;allreceived dex am ethasone10m g F ox-G eim an O ndansetronpo24m g (8m g Q 8) ivqdwhilereceiving the 47 2001 D BR CT BM T;TBI O ndansetroniv32m g qd 5-HT3antagonist;also, N R /N R 28%m ale SingleCenter Parallel G ranisetronpo2m g (1m g Q 12) benz odiaz epineswere N R 5 allowedasneededfor sleep. Antiemetics Page 39 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Screened/ W ith drawn/ Setting Eligible/ L ostto fu/ H esketh rating Enrolled A nalyz ed O th erpopulationch aracteristics M eanweight,kg:78kg allogenic transplant3% autologoustransplant97% Inpatienttreatm entsetting 73% O utpatienttreatm entsetting 27% Historyof m oderate/severenausea72% Historyof vom iting:57% Historyof anticipatorynausea/vom iting 12% Conditioning regim ens:TBI-containing 26% Conditioning regim ens:Chem oonly74% F ox-G eim an preparativeregim en: 2001 N R /N R /102 6/0/102 STAM P V:33% SingleCenter TBI/VP/CY:25% 5 TAN C:15%; BU /CY:11% BE AM :4%; BCN U /VP/CY:2% ICE :2% Carboplatin/VP:2% Carboplatin/M TZ/CY:2% M M T:2% Thiotepa/CY:1% TBI/CY:1% Antiemetics Page 40 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating R esults O ndpo24vsO ndiv32vsG ranpo2 Com pleteresponse(CR :noorm ildnausea(ptabletoeat;reasonableintake)andnorescueantiem eticsused) D ay1:95% vs92% vs92%,N S D ay2:69% vs69% vs77%,N S D ay3:73% vs75% vs81%,N S D ay4:35% vs32% vs45%,N S D ay5:27% vs30% vs25%,N S D ay6::32% vs32% vs25%,N S D ay7:45% vs31% vs15%,N S D ay8:35% vs10% vs8%,N S Com positescore(overall-D ays1-8):48% vs49% vs47%,N S M ajorR esponsescore(1vom iting episodeorif novom iting,m oderatenausea(intakesignificantlydecreased;ptcaneat)with rescueallowed: F ox-G eim an N orm aliz edfor8days:82% vs81% vs84%,N S 2001 M ajorresponse(M R ):1episodeof vom iting orm oderatenausea(intakesignificantlydecreased,butpatientcaneat)with rescueallowed SingleCenter D ay1:2% vs6% vs8%,N S 5 D ay2:31% vs24% vs17%,N S D ay3:21% vs19% vs11%,N S D ay4:42% vs42% vs47%,N S D ay5:58% vs47% vs55%,N S D ay6:46% vs41% vs60%,N S D ay7:28% vs54% vs57%,N S D ay8:44% vs65% vs70%,N S F ailure(>4episodesof nausearegardlessof nauseaorrescueantiem etic use) Com positescore:4. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating A dverse events C om m ents PatientswerestratifiedbygenderandbyTBI-containing vs. Ptpopulationweretoreceivechem oor chem oradiotherapytreatm entspriortostem celltransplantation. Chem o TotalpoptsvsO ndIV regim ens:Preparativeregim ensincludedSTAM P V;TBI/etoposide Totalwithdrawals:7. Theadditional5 totalAU C = 30;carboplatine/m itox antrone(M TZ)/CY;M M T (paclitax el150 withdrawals"refusedtocontinuetheprotocolduetopoornauseaand/or m g/m ^2perdaycontinuousIV infusion[CIV]over96hoursondays-6,-5,- em esiscontrol. Antiemetics Page 42 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear A ge Setting A llow oth er G ender H esketh rating Design Subpopulation Intervention m edication R un-in/W ash -out Eth nicity G ebbia 59 1994a O penR CT ondansetroniv24m g none N o N R /N R 64%m ale SingleCenter Parallel granisetroniv3m g N R 5 G ebbia 56 1994b O penR CT ondansetroniv16m g none N o N R /N R 21%m ale SingleCenter Parallel G ranisetroniv3m g N R 3 Antiemetics Page 43 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Screened/ W ith drawn/ Setting Eligible/ L ostto fu/ H esketh rating Enrolled A nalyz ed O th erpopulationch aracteristics D elayed:91% Prim arytum or: headandneck47% lung 16% G ebbia urinarybladder7% 1994a ovary7% N R /N R /182 16/0/166 SingleCenter stom ach 6% 5 endom etrium 6% vulva7% breast3% testis1% sarcom a1% Prim aryTum or: Breast60% G ebbia L ung 15% 1994b N R /N R /164 8/0/158 O vary8% SingleCenter Stom ach 6% 3 N on-Hodgkinlym phom a9% M elanom a1% Antiemetics Page 44 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating R esults O ndansetronvsG ranisetron Acuteem esisresponserates:com plete,m ajor,m inor,andfailure M ajorresponse:29% vs24%,N S M inorresponse:14% vs12%,N S F ailure:5% vs15%,N S Com pleteresponse:noem esis(acute):52% vs49%,N S G ebbia D elayedem esisresponserates:com plete,m ajor,m inor,andfailure 1994a Com pleteresponse :39% vs36%,N S SingleCenter M ajorresponse:24% vs22%,N S 5 M inorresponse:21% vs28%,N S F ailure:16% vs14%,N S N auseaseverity N onausea:acute:74% vs79%,N S N oorm ildnausea:delayed:53% vs45%,N S Com pleteresponseinptsundergoing fractionatedchem o N oem esisinptsundergoing fractionatedchem o:D ays2-5:43% vs35%,N S O ndansetronvsgranisetron Acuteem esisresponserates:Com plete,m ajor,m inor,failure F ailure:≥ 6em etic episodes:3% vs4%,N S M inorresponse:3-5em etic episodes:6% vs10%,N S G ebbia M ajorresponse:1-2em etic episodes:22% vs19%,N S 1994b Com pleteresponse:noem etic episodes:69% vs67%,N S SingleCenter D elayedem esisresponserates:Com plete,m ajor,m inor,failure 3 M ajorresponse,days2-5:15% vs20%,N S Com pleteresponse:noem esisdays2-5:45% vs52%,N S Ptsex periencing nonausea: Acute:50% vs45%,N S D elayed:31% vs37%,N S Antiemetics Page 45 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating A dverse events C om m ents G ebbia Ptsstratifiedaccording tolength of chem o(singledayvs. Ptswith fractionatedchem o Headache:9% vs4%,N S SingleCenter receivedO ndpo8m g bid(total= 16m g)orG raniv3m g onthedayswith Constipation:17% vs7%,N S 5 chem oafterday1. Allptswererequiredtoreceiveepidox orubicin ≥ 75m g/m 2,dox orubicin≥ 40m g/m 2,cyclophospham ide ≥ 600m g/m 2iv,IF X ≥ 3g/m 2(study2). In G ebbia Study2,m ostpatientsreceivedaCM F regim en(cyclophospham ide600 1994b m g/m 2,m ethotrex ate40m g/m 2,and5-fluorouracil[5-F U ]600m g/m 2), SingleCenter F AC/F E C regim en(5-F U 600m g/m 2,cyclophospham ide600m g/m 2, 3 epidox orubicin75-90m g/m 2ordox orubicin40-60m g/m 2),orifosfam ide3- 5g/m 2plusvinorelbine25-30m g/m 2. Antiemetics Page 46 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear A ge Setting A llow oth er G ender H esketh rating Design Subpopulation Intervention m edication R un-in/W ash -out Eth nicity Corticosteroids (dex am ethasoneor m ethylprednisolone) couldbegivenas replacem entor G ralla O ndansetroniv32m g +dex orm - m aintenancetherapy 61. Antiemetics Page 47 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Screened/ W ith drawn/ Setting Eligible/ L ostto fu/ H esketh rating Enrolled A nalyz ed O th erpopulationch aracteristics M eanbodyweight= 74kg G ralla M eanalcoholunits/week= 6. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating R esults O ndansetronvsG ranisetron Totalcontrol(noem esis,nonauseaof anyseverity,andnouseof antiem etic rescuem edication)over24h postcisplatinadm inistration) F orallpatients:58. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating A dverse events C om m ents PatientswererequiredtoreceiveIV cisplatinof ≥ 60m g/m 2overaperiod notex ceeding 3hours. N oadditionalcisplatinwasadm inistereduntil24 O ndansetronvsG ranisetron hourshadelapsed. Thetim ing of allpost-chem oassessm entsand Asthenia:18. Thisstudyonlyreportednum bersforAE s Patientsex periencing anyAE :85. Thetwom ostcom m onlyused Both drugs antiem etic rescuem edicationsusedwereprochlorperaz ineand W ithdrawalsduetoAE s:notstratifiedbydrug:0.