Presentation on theme: "Sponsored by Chemotherapy SIG Session Coordinator/Speaker"— Presentation transcript:
1 Sponsored by Chemotherapy SIG Session Coordinator/Speaker Institute of Learning 2011Sponsored by Chemotherapy SIGSession Coordinator/SpeakerMillie Toth, MS, RN, AOCNSpeakersMyra Davis-AlstonNousheen Samad, PharmD, BCOP
2 HOT TOPICS IN CHEMOTHERAPY 2011 ObjectivesDiscuss best practice in chemotherapy administration, including sequencing of drugs and patient support in chemotherapy drug shortage situations.Describe appropriate steps to address environmental monitoring and employee medical surveillance when working with hazardous drugs.HOT TOPICS IN CHEMOTHERAPY 2011
3 Chemotherapy administration HOT TOPICS IN CHEMOTHERAPY 2011“Best Practice”InChemotherapy administrationMyra Davis-Alston, RN,MSN/Ed, OCN,CRNIOncology Staff NurseLas Vegas, NV.November 5, 2011
4 HOT TOPICS IN CHEMOTHERAPY 2011 OBJECTIVESReview Expert Opinions on “Best Practice” for administration of Cancer ChemotherapyDevelop an action plan for integrating “Best Practice” guidelines in your clinical practice.Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important.Introduce each of the major topics.To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next.“Best Practice” in chemotherapy administration
5 HOT TOPICS IN CHEMOTHERAPY 2011 American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards“Best Practice” in chemotherapy administration
6 Develop Chemotherapy Safety Standards HOT TOPICS IN CHEMOTHERAPY 2011Goals:Develop Chemotherapy Safety StandardsStandardization of careReduce risk of errorsIncrease efficiencyProvide a framework for “Best Practice”“Best Practice” in chemotherapy administration
7 Requirements for ASCO/ONS Chemotherapy Administration Standards CRITERIAApplicable to diverse outpatient hematology/oncology practice settingsUnderstandable and clinically intuitiveRealistic to achieve with existing or reasonable resource expectationsValid, based on scientific evidence or strong expert consensusJacobson, J., et al. (2009) American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards“Best Practice” in chemotherapy administration
8 Requirements for ASCO/ONS Chemotherapy Administration Standards CRITERIA – continuedReliable, allowing consistent implementation and assessment over time and across sitesMeasureable, allowing performance according to the standard to be assessed for both internal quality assessment and external quality monitoringActionable, informing practice processes, policies or proceduresJacobson, J., et al. (2009) American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards“Best Practice” in chemotherapy administration
9 Definitions for ASCO/ONS Chemotherapy Administration Safety Standards HOT TOPICS IN CHEMOTHERAPY 2011Definitions for ASCO/ONS Chemotherapy Administration Safety StandardsCHEMOTHERAPY“all antineoplastic agents used to treat cancer, given through oral and parenteral routes or other routes as specified in the standard.Types include targeted agents, alkylating agents, antimetabolites, plant alkaloids and terpenoids, topoisomerase inhibitors, antitumor antibiotics, monoclonal antibodies, and biologic and related agents. Hormonal therapies are not included in the definition of chemotherapy for the standards.”Jacobson, J., et al. (2009) American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards“Best Practice” in chemotherapy administration
10 Multidisciplinary consensus-building process HOT TOPICS IN CHEMOTHERAPY 2011Multidisciplinary consensus-building process“Best Practice” in chemotherapy administration
11 Overview 1 2 3 HOT TOPICS IN CHEMOTHERAPY 2011 Familiarize yourself with ASCO/ONS Chemotherapy Administration safety standards2Explore how the standards apply to individual practice settings3Develop strategies to integrate “Best Practice” to individual work settings“Best Practice” in chemotherapy administration
12 A QUESTION FOR YOU HOT TOPICS IN CHEMOTHERAPY 2011 “Best Practice” in chemotherapy administration
13 Staffing-Related Standards Patient consent and Education HOT TOPICS IN CHEMOTHERAPY 2011Which of the following are not included in ASCO/ONS Chemotherapy Administration Safety StandardsStaffing-Related StandardsPatient consent and EducationSequencing of Drug AdministrationGuidelines on use of Personal Protective Equipment (PPE)Jacobson, J., et al. (2009) American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards“Best Practice” in chemotherapy administration
14 ASCO/ONS Chemotherapy Administration Safety Standards HOT TOPICS IN CHEMOTHERAPY 2011ASCO/ONS Chemotherapy Administration Safety StandardsStaffing Related StandardsChemotherapy Planning: Chart Documentation StandardsGeneral Chemotherapy Practice StandardsChemotherapy Order StandardsDrug PreparationPatient Consent and EducationChemotherapy AdministrationMonitoring and Assessment“Best Practice” in chemotherapy administration
15 A QUESTION FOR YOU HOT TOPICS IN CHEMOTHERAPY 2011 “Best Practice” in chemotherapy administration
16 Nurse-Patient staffing ratio HOT TOPICS IN CHEMOTHERAPY 2011Which of the following guidelines are not identified in Staffing Related Standards in ASCO/ONS Chemotherapy Administration Safety StandardsPolicies, procedures, and or guidelines for verification of training and continuing education for clinical staff.Nurse-Patient staffing ratioCurrent certification in basic life supportWritten Orders for parenteral and oral chemotherapyKeep it brief. Make your text as brief as possible to maintain a larger font size.Jacobson, J., et al. (2009) American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards“Best Practice” in chemotherapy administration
17 Staffing-Related Standards HOT TOPICS IN CHEMOTHERAPY 2011Staffing-Related StandardsPolicies, Procedures and/or guidelines for verification of trainingChemotherapy Drug Preparation prepared by qualified staffComprehensive education program for new staff-including competency assessmentStandard mechanism for monitoring competency at specified intervalCurrent Certification in basic life support“Best Practice” in chemotherapy administration
18 A question for you HOT TOPICS IN CHEMOTHERAPY 2011 “Best Practice” in chemotherapy administration
19 HOT TOPICS IN CHEMOTHERAPY 2011 Which of the following guidelines are NOT included in the ASCO/ONS Chemotherapy Administration Safety Standards?1. Alternative and or drug substitution for standard drugs during national drug shortages2. Confirm with the patient his/her planned treatment, drug route, and symptom management3. Verify accuracy of the drug including sign in record to indicate verification was done4. A licensed Independent practitioner is on site and immediately available during all chemotherapy administration.“Best Practice” in chemotherapy administration
20 Working Toward Best Practice Microsoft Engineering ExcellenceHOT TOPICS IN CHEMOTHERAPY 2011Working Toward Best PracticeApply ASCO/ONS ChemotherapySafety StandardsInvolve all stake holderProjects Worked OnGet Familiar with Safety StandardsTime Spent“Best Practice” in chemotherapy administrationMicrosoft Confidential
21 Summary Define your challenges Set realistic expectation HOT TOPICS IN CHEMOTHERAPY 2011SummaryDefine your challengesTechnological as well as personalSet realistic expectationMastery is not achieved overnightKeep your eye on the goalMentorship programs“Best Practice” in chemotherapy administration
22 Microsoft Engineering Excellence HOT TOPICS IN CHEMOTHERAPY 2011ResourcesAmerican Society Of Clinical OncologyOncology Nursing Society“Best Practice” in chemotherapy administrationMicrosoft Confidential
23 Chemotherapy Drug Shortage HOT TOPICS IN CHEMOTHERAPY 2011Chemotherapy Drug ShortageNousheen Samad, PharmD, BCOPMD Anderson Cancer Center, Houston, TXNovember 5, 2011
24 A QUESTION FOR YOU HOT TOPICS IN CHEMOTHERAPY 2011 Chemotherapy Drug Shortage
25 A drug shortage may occur due to: Lack of drug discovery by pharmaceutical companiesOutsourcing of drug manufacturing outside the United StatesContamination of a drug during manufacturing resulting in a large-scale recallFDA regulations on drug marketing and distributionChemotherapy Drug Shortage
26 Drug shortages can result in: Significant delays in patient careSubsequent shortage of alternate drug within the same classLarge upsurge in drug priceAll of the aboveChemotherapy Drug Shortage
27 The Past and the Present HOT TOPICS IN CHEMOTHERAPY 2011The Past and the Present1982: Johnson & Johnson recall - Tylenol®2008: Baxter recall – heparin2010: Amgen recall – Procrit®Currently: one of the most severe shortages for cancer treatment in last few decades74% involving sterile injectables11% of drugs on shortage list are oncologic agentsWhile shortages include a variety of drugs (such as antimicrobials and anesthetics), the FDA reports that about 74% of shortages involve sterile injectablesInjectables: More issues with stability than oral dosage formsMany are the result of quality issues - Injectables take longer to manufactureChemotherapy Drug Shortage
28 Complex Manufacturing Process HOT TOPICS IN CHEMOTHERAPY 2011Complex Manufacturing ProcessMore resource-intensive processOne production line used for multiple agentsFocused on productions of items with high profit marginsLack of available medically acceptable alternativesIncrease in government control: “Red tape”Transition: so why now? Why are we facing this issue so acutely now?Today’s drug manufacturing is a more resource-intensive processEach production line used for multiple agentsProblem with one batch can effects several drugs at onceFocus on productions of items with high profit marginsOlder products get less precedent in production line-upLack of available medically acceptable alternativesMany novel agents with unique mechanisms and narrow spectrum of activity (eg MoAbs)Increase in government control: “Red tape”“red tape” increased oversight by FDA has helped shrink the profit margin so much that some manuf have had to shut down their plantsChemotherapy Drug Shortage
29 HOT TOPICS IN CHEMOTHERAPY 2011 Drug RecallProduct is removed from the market due to a defect or has the potential to cause harmManufacturing issuesMisbranding, contamination, adulterationOverseen by Food and Drug Administration (FDA)Can be initiated by company or FDAIncreasing in number and frequencyChemotherapy Drug Shortage
30 HOT TOPICS IN CHEMOTHERAPY 2011 Drug ShortageA period of time when the total supply of all versions of a drug available at the user level will not meet the current demand for the drug at the user levelRecall of raw materials used in formulating agentIssues relating to manufacturingUsually no advance warningOccurs over short period of time (acute)Chemotherapy Drug Shortage
31 Top Oncologic Agents in Shortage HOT TOPICS IN CHEMOTHERAPY 2011Top Oncologic Agents in ShortageDrug name# of manufacturersReason for shortageBleomycin4Manufacturing delays, increased demandCarmustine1Manufacturing delaysCisplatin3CytarabineManufacturing delays, raw material issuesDoxorubicinEtoposideLeucovorinMechlorethamineTransfer to new manufacturing plantYou may or may not have felt the effects of these shortages based on your hospital’s supply of these agents – and there usage.Most problematic aspect of the drug shortage is that many of these agents are the standard of care in oncology – Matthew Farber qoute (not direct)Just about every cancer has been affected by these shortages (Matthre Farber): colorectal, leukemia, breast, Hodgkin, Lung, testicular, prostate, esophageal, ovarian, pancreaticChemotherapy Drug Shortage
32 Impact of Shortages on Healthcare HOT TOPICS IN CHEMOTHERAPY 2011Impact of Shortages on HealthcareDisproportionate effect on smaller facilitiesAdded staff time dealing with shortageIncreased cost per item due to short supplyRipple effect: increased demand on alternative agentsStockpiling/hoarding by some institutionsInterruption in clinical trialsMedications errorsDealing with patients’ frustrations and blameDisproportionate effect on smaller facilitiesOrder on “as needed” basisMay not have the buying power of larger institutionsLarger hospitals: Carry stock items & use multiple suppliersMedication errors: dosage errors can occur when the doctors are forced to switch patients to unfamiliar agents (not standard of care)Chemotherapy Drug Shortage
33 Impact of Shortages on Patient Care HOT TOPICS IN CHEMOTHERAPY 2011Impact of Shortages on Patient CareDelay in drug therapyUse of less effective alternate therapyProlonged hospital staysIncrease cost to patientInsurance coverageTraveling to alternate treatment centerEmotional impactEmergence of “grey market”Delay in drug therapy: anecdotal reports that some patients are not getting the drugs they should be, that they are not getting all the drugs they need, or are not getting any drugs at all for a time (Bona E Benjamin) - cont. qoute – that means they are not getting the best outcome that they should.Insurance coverage: alternative agent not reimbursed by insurance companiesEmotional impact – difficult to measureGrey market: imported drugs that are of unknown purity and available typically on at high markups (10 to 1,000 times)“grey” market vendors: Create artificial shortages, Re-sell the product back to users at inflated prices- The profitability of pharmaceuticals and the pharmaceutical industry attracts vendors who may create artificial shortages by selectively purchasing excessive quantities of products and thereby depleting the available stock. These vendors then re-sell the products back to the users at inflated prices.Chemotherapy Drug Shortage
34 Causes of Drug Shortages HOT TOPICS IN CHEMOTHERAPY 2011Causes of Drug ShortagesInterruption in drug supply infrastructureShortage of raw materialManufacturing issuesNatural disasterVoluntary recall of already manufactured itemsCauses….”MULTIFACTORIAL”Drug supply infrastructure – aka supply chain?Shortage of raw materialShortage of natural source to extract fromInterruption of importation from sources outside USMultiple drug manufacturer using same raw materialManufacturing issuesMachinery, staffing, citationsNatural disasterUnexpected damage to facilities interrupt operationsRaw material shortages may have a profound impact on drug supply. This is especially true when multiple manufacturers are producing a drug product from which there is only one source of raw materials.Problems can also arise when the raw materials are difficult to process (eg, the raw material must be extracted froma natural source, such as a tree bark)An estimated 80% of the raw materials used in pharmaceuticals comes from outside the US (ASHP report 2009). Availability problems can arise when armed conflict or political upheaval disrupts trade, animal diseases contaminate tissue from which raw materials are extracted, climatic and other environmental conditions depress the growth of plants used to product raw materials, or raw materials are degraded or contaminated during transport.80% from outside USConflictDiseaseClimate changesMachinery: antiquated equipmentStaffing: lack of experienced manufacturing personnelCitations: production halted by FDAVoluntary recall of already manufactured items due to Production issuesChemotherapy Drug Shortage
35 Causes of Drug Shortages (cont.) HOT TOPICS IN CHEMOTHERAPY 2011Causes of Drug Shortages (cont.)Manufacturer discontinuationManufacturer rationingRestricted distributionIndustry consolidationManufacturer discontinuationLack of financial incentive or demandManufacturer rationingTemporary or permanent reduction in production to shift production or re-allocate resourcesRestricted distributionLimits supplies to select patient populations for which benefits outweigh risksIndustry consolidationCompany mergers result in discontinuations in order to narrow product lineChemotherapy Drug Shortage
36 Causes of Drug Shortages (cont.) HOT TOPICS IN CHEMOTHERAPY 2011Causes of Drug Shortages (cont.)Market shiftBrand to genericUnexpected demandNew indication or change in prescribingDisease outbreakJust-in-time inventoriesMarket shiftShift from brand to generic product may cause a decrease in manufacturing of the innovator productUnexpected demandNew indication or unlabeled usesChange in prescribing or clinical practiceDisease outbreak (eg. anthrax)Just-in-time inventoriesIncreased risk for sudden changes in supply or demandChanges in product form or formulation: Sustained release productShifts in demand may be further complicated when the manufacturing process for the product is time consuming or raw materials needed to produce it are limited (blood-based products)Prime Vendors & Just-in-Time Inventories: Reduces amount of product in supply chain, Removes “buffer” provided by stockpiles- The increased use of prime vendors may have contributed to the drug shortage situation by reducing the amount of product available in the supply chain. It is no longer easy to weather shortages by relying on stockpiled inventories because both wholesalers and health systems maintain a minimum levels of stock. As a result, manufacturer supply issues are transmitted directly to the user without the benefit of an inventory buffer, thereby increasing the number of short-term shortages that may impact institutions.Chemotherapy Drug Shortage
37 Drug Shortage Oversight HOT TOPICS IN CHEMOTHERAPY 2011Drug Shortage OversightDepartment of Health and Human ServicesThe Food and Drug AdministrationProtect the public health by ensuring safety, effectiveness, and security of drugs, vaccines, and other biologic products.Regulates medical devices, the food supply, cosmetics, dietary supplements, and products that emit radiation.Can allow drug importation outside of normal channels to respond to a crisis.Center for Drug Evaluation & Research (CDER)Drug Shortage Program:Facilitate prevention and resolution of shortages by collaborating with FDA experts, industry, and external stakeholdersProvide drug shortage information to the public, healthcare professional organizations, patient groups, and other stakeholdersCDER: Center for Drug Evaluation and Research oversees the DSPDrug Shortage Program (DSP) began in 1999Mission: to address potential and actual drugshortages*Currently 4 full time staff and CoordinatorWithin FDA/CDER• DSP works with– Review division(s) in OND that regulates thetherapeutic areas for the drug– Office of Generic Drug Products– Office of New Drug Quality Assessment– Office of Biotechnology Products– Office of Compliance (Office of Regulatory Affairs)– OtherChemotherapy Drug Shortage
38 Drug Shortage Oversight HOT TOPICS IN CHEMOTHERAPY 2011Drug Shortage OversightVery limited authorities directly related to drug shortagesLimited notification requirementResponse from FDA is usually secondaryMitigate a problem that has already occurredNo consequence for failure to notifyVoluntary participation of industryFDA cannot dictate the production quantityLimited notification requirementOnly requirement is notification of sole source discontinuationChemotherapy Drug Shortage
39 FDA / CDER / DSP Work with manufacturer to address issues HOT TOPICS IN CHEMOTHERAPY 2011FDA / CDER / DSPWork with manufacturer to address issuesEncourage other firms to increase productionExpedite resolving issues related to shortagesAllow release of medically necessary productsTemporarily import drug from unapproved sources“Flexibity” Allow release of medically necessary products with extra oversight and alerts for healthcare professionals and patientsChemotherapy Drug Shortage
40 Drug Shortages Summit November 2010 – Bethesda, Maryland HOT TOPICS IN CHEMOTHERAPY 2011Drug Shortages SummitNovember 2010 – Bethesda, MarylandAmerican Society of AnesthesiologistsAmerican Society of Clinical Oncology (ASCO)American Society of Health-System Pharmacists (ASHP)Institute for Safe Medication Practices (ISMP)Chemotherapy Drug Shortage
41 Drug Shortages Summit Identified major cause of shortages: HOT TOPICS IN CHEMOTHERAPY 2011Drug Shortages SummitIdentified major cause of shortages:Fewer manufacturers producing sterile injectablesProduction-line problems, delays, discontinuationsIncreased FDA inspections of injectablesRising worldwide demand for chemotherapyNo law requiring manufacturers to report to FDAThe summit found that a major cause of shortages is that fewer manufacturers are producing the sterile injectables (most of which are generic) thereby limiting contributors to the supply chain --- not enough resiliency in the supply chainFewer manufacturers producing sterile injectablesThe ones who are making them have limited capacity, they often discontinue these older agents in favor of newer/more profitable agents, when shortage occurs – limited ability of remaining firms to meet the shortfallProduction-line problems, delays, discontinuationsEx: Teva Pharmaceuticals & Hospira Inc. -- >Shut down some production lines after not meeting quality control standardsIncreased FDA inspections of injectable products to meet GMP - based on “higher likelihood of harm” to patientsRising worldwide demand is also putting pressure on the system (due to globalization of drugs)Manuf are not required by law to alert the FDA when they d/c a product or when the production process is interrupted – this often leaves medical centers “off-guard” – frantically searching for new sources to obtain the drug* the FDA cannot force a manuf to produce a product and there is no penalty for not notifying the FDA when a product is d/c’d.Chemotherapy Drug Shortage
42 Drug Shortages Summit Recommendations: HOT TOPICS IN CHEMOTHERAPY 2011 FDA be given the statutory authority to require manufacturers toReport any disruption in supply chainInterruption in supply of raw materialsInterruption in manufacturing processProvide notification 9 to 12 months before a drug is pulled off the marketHave more than one production site for a sole, essential drugReport any disruption in supply chainInterruption in supply of raw materialsInterruption in manufacturing processInterruption in active pharmaceutical ingredientsChemotherapy Drug Shortage
43 Legislative Action Preserving Access to Life-Saving Medications Act HOT TOPICS IN CHEMOTHERAPY 2011Legislative ActionPreserving Access to Life-Saving Medications ActNew bill proposed February 2011Amendment to Federal Food, Drug, and Cosmetic ActWill provide FDA with better capacity to prevent drug shortagesStatus: Currently in the first step in the legislative processGOAL: To increase transparency within the entire supply processSponsor: Sen. Amy Klobuchar [D-MN]Senate bill: gives the FDA the authority to require early notification from pharmaceutical companies when they decide to limit or discontinue production of prescription drugs Increase transparency of the entire supply processChemotherapy Drug Shortage
44 Preserving Access to Life-Saving Medications Act HOT TOPICS IN CHEMOTHERAPY 2011Preserving Access to Life-Saving Medications ActPreserving Access to Life-Saving Medications ActManufacturer shall notify FDARegarding manufacturing interruptions that could result in drug shortages at least 6 months in advanceCivil monetary penalties for lack of reportingFDA shall publish informationRegarding manufacturing delays and actual shortages on their websiteDistribute this information to health care providers and patient organizationsExpand current statutory language related to reporting of information to FDA regarding manufacturing interruptions that could result in drug shortagesIncreased communication from FDA regarding drug shortages, including providing shortage information to healthcare providersCalls for FDA to develop evidence-based criteria for identification of agents vulnerable to shortageCalls for FDA to work with manufacturers to create “continuity of supply” plans that include processes to address drug shortagesReporting: In real time and describe plans to address the shortageChemotherapy Drug Shortage
45 Preserving Access to Life-Saving Medications Act HOT TOPICS IN CHEMOTHERAPY 2011Preserving Access to Life-Saving Medications ActFDA shall develop criteriaFor identification of drugs susceptible to shortageFDA shall collaborate with manufacturersTo create plans for continued supply of medically necessary drugsFDA shall report to CongressOn an annual basis describing the actions taken to address drug shortagesChemotherapy Drug Shortage
46 Other Possible Solutions HOT TOPICS IN CHEMOTHERAPY 2011Other Possible SolutionsASHP: Implement government incentive programHOPA: Implement system for emergency importation of drugsManufacturers: implement strategies to ensure uninterrupted supply schedulesHealthcare institutions: proactive in obtaining stock by anticipating needs of patients without hoardingHealthcare Distribution Management Association (HDMA)McKesson Specialty Care Solutions + FDAIn a recent survey, HOPA members recommended that the association lobby the FDA for allowance of emergency importing of drugs to deal with unanticipated shortages.HDMA: Collaborative advocacy effort with other associations to discuss causes/trends of shortages and explore mitigation strategiesManufacturers: Should plan ahead!! by adding redundancy to manufacturing & raw material supply to prevent shortages of medicallynecessary drugs• Commitment to quality: proactively identify & promptly correct issues• Prevent sudden lack of lifesaving medications for consumer• Notify FDA as soon as aware of an issue that could impact supply. Contact Drug Shortage Program at– 38 shortages prevented in 2010 due to early notification by firms– 99 shortages prevented in 2011 so far due to early notificationWhat can we do as Healthcare professionals: support current bills!Chemotherapy Drug Shortage
47 Other Possible Solutions HOT TOPICS IN CHEMOTHERAPY 2011Other Possible SolutionsPartnering with other hospitals/practice sitesShare drug supplyShare patient loadRegular communication with vendorsCollaborate with more than one vendorHonest communication with patientsExpectations for shortageFacilitating change in plan of careChemotherapy Drug Shortage
48 Information on Drug Shortages HOT TOPICS IN CHEMOTHERAPY 2011Information on Drug ShortagesUS Food and Drug Administration (FDA)American Society of Health-System Pharmacists (ASHP)Drug Product Shortages Management Resource CenterOther organizations: ASCO, ISMPIndividual hospital shortage listSpecific to each institutionASCO: American Society of Clinical OncologyISMP: Institute for Safe Medication PracticesFDA Webinar on Prescription Drug ShortagesSept. 30, 2011, 11:00 a.m.Chemotherapy Drug Shortage
49 Sequencing of Chemotherapy HOT TOPICS IN CHEMOTHERAPY 2011Sequencing of Chemotherapy… does it really matter??Nousheen Samad, PharmD, BCOPMD Anderson Cancer Center, Houston, TXNovember 5, 2011
50 A QUESTION FOR YOU HOT TOPICS IN CHEMOTHERAPY 2011 sequencing of chemotherapy … Does it really matter ??
51 The appropriate sequencing of chemotherapy agents: Can decrease the toxicity of a chemo regimenCan increase the efficacy of a chemo regimenIs not clear for many chemo regimensAll of the abovesequencing of chemotherapy … Does it really matter ??
52 Combination Chemotherapy HOT TOPICS IN CHEMOTHERAPY 2011Combination ChemotherapyIncrease cytotoxic effectAttack different biochemical targetsOvercome drug resistanceOptimize dose of each agentTake advantage of kinetics of tumor growthBiochemical synergyMaintain acceptable level of toxicitysequencing of chemotherapy … Does it really matter ??
53 Combination Chemotherapy HOT TOPICS IN CHEMOTHERAPY 2011Combination ChemotherapyIncreased risk of drug interactionsPhysiologic effects of each agent on cell cyclePharmacodynamic/pharmacokinetic interactions between the agentsIn vitro versus in vivoClinically relevant versus non-relevantSequencingOrder of administrationSame day versus next day administrationExample: Cisplatin and paclitaxelCan this be extrapolated?sequencing of chemotherapy … Does it really matter ??
54 Cell Cycle HOT TOPICS IN CHEMOTHERAPY 2011 Mitosis and the Cell Division CycleCells that are growing and dividing go through a repeating series of events called the cell division cycle (or cell cycle). During the first phase (G1), the cell grows and prepares for DNA replication, which occurs in the subsequent S phase. Further growth takes place in the G2 phase, and finally mitosis occurs in the M phase.• G1, S, and G2 are collectively called interphase.• G1 stands for gap 1, or presynthesis; S for synthesis; G2for gap 2, or postsynthesis.• M is the mitotic division phase.sequencing of chemotherapy … Does it really matter ??
55 Synergism versus Antagonism HOT TOPICS IN CHEMOTHERAPY 2011Synergism versus AntagonismSynergism:Exerting a greater than the expected additive effect when using drugs in combinationAntagonism:Observing a less than expected additive effectsequencing of chemotherapy … Does it really matter ??
56 Chemotherapy Sequencing HOT TOPICS IN CHEMOTHERAPY 2011Chemotherapy SequencingVery little objective data publishedLaboratory dataAnimal studiesExtrapolation of data to other agents in same classDrug databases may not have most accurate dataMay be synergistic or antagonisticsequencing of chemotherapy … Does it really matter ??
57 Leucovorin Leucovorin BEFORE 5-fluorouracil HOT TOPICS IN CHEMOTHERAPY 2011LeucovorinLeucovorin BEFORE 5-fluorouracilIncreased cytotoxicity and efficacy of 5-fluorouracil by stabilizing thymidylate synthaseLeucovorin AFTER MethotrexateDecreased toxicity from methotrexate by rescuing normal cellsIf reversed: efficacy of methotrexate is decreasedsequencing of chemotherapy … Does it really matter ??
58 Sequencing Resulting in Lower Toxicity HOT TOPICS IN CHEMOTHERAPY 2011Sequencing Resulting in Lower ToxicityPaclitaxel → Cisplatin↓ neutropeniaGemcitabine → CisplatinDocetaxel → VinorelbineDocetaxel → TopotecanDoxorubicin → DocetaxelDoxorubicin/Epirubicin → Paclitaxel↓ myelosuppression + mucositisLiposomal doxorubicin → VinorelbineTopotecan → Cisplatin/Carboplatin↓ neutropenia + thrombocytopeniaTopotecan → CisplatinCyclophosphamide → Paclitaxel↓ cytopeniasIfosfamide → Docetaxel↓myelosuppressionIrinotecan → 5-fluorouracil↓neutropenia + diarrheasequencing of chemotherapy … Does it really matter ??
59 Sequencing Resulting in Higher Efficacy HOT TOPICS IN CHEMOTHERAPY 2011Sequencing Resulting in Higher EfficacyIrinotecan → 5-fluorouracil↑ EfficacyFludarabine → CytarabinePemetrexed → GemcitabinePaclitaxel → Gemcitabine↑ SynergyCisplatin → Irinotecan↑ Response rate5-fluorouracil → MethotrexateLiposomal doxorubicin → Docetaxel↑ TolerabilityGemcitabine → Cisplatin↑ Increase platinum-DNA adductssequencing of chemotherapy … Does it really matter ??
60 Clinical Application of Sequencing HOT TOPICS IN CHEMOTHERAPY 2011Clinical Application of SequencingSequence of agents used in clinical trialFor regimens with no specified sequenceAdminister based on patient needsBolus followed by continuous infusion (outpatient)Develop institutional standards based on the clinical information that is knownDevelop order sets with built-in sequence to ensure correct sequencing“Best Practice” in chemotherapy administration
61 Environmental monitoring In your work environment HOT TOPICS IN CHEMOTHERAPY 2011Environmental monitoringandMedical SurveillanceIn your work environmentMille A. Toth, MS, RN, AOCNSenior Nursing InstructorM. D. Anderson Cancer CenterHouston, TexasNovember 5, 2011
62 A QUESTION FOR YOU HOT TOPICS IN CHEMOTHERAPY 2011 Environmental monitoring and Medical Surveillance
63 HOT TOPICS IN CHEMOTHERAPY 2011 NIOSH and OSHA guidelines recommend that institutions provide a medical surveillance program. How does your institution support this?My institution provides “base-line” initial employment physical and annual / periodical laboratory evaluationsMy institution states the use of closed systems, PPE and education provided to staff eliminates the need for medical surveillance programMy institution offers no established form of medical surveillance and does not provide NIOSH recommended closed systemsI don’t know how my institution addresses the NIOSH and OSHA guidelines for Medical SurveillanceEnvironmental monitoring and Medical Surveillance
64 History of Safe Handling Advent of Modern day chemotherapyLoius Goodman and Alfred Gillmon use nitrogen mustard to treat non-Hodgkin’s LymphomaFirst review of carcinogenic potential of anticancer drugs“The carcinogencity of anticancer drugs: A Hazard in Man”First case report of occupational exposure risk with HDs“Mutagenicity in the urine of nurses handling cytostatic agents”1981First published guidelines for handling HDs“Developing guide-lines for working with antineoplastic drugs”19421983American Medical Association guidelines for HDs“Guidelines for handling parenteral antineoplastics”1985Risk defined for occupational exposure to HDs“Risk of handling injectable antineoplastic agents”American Society of Hospital Pharmacists Technical advisory bulletin (TAB) on handling cytotoxic and hazardous drugsOSHA Technical Manual: Control-ling occupational exposure to HDs Chapter 21. (OSHA instruction CPL B CH4)OSHA Technical Manual Update: Controlling occupational exposure to HDsOSHA instruction TED A Section VI. Chapter 2First US evaluation of PhaSeal “Evaluation of the PhaSeal hazardous drug containment system”USP <797> ”Pharmaceutical compounding-Sterile preparations”American Society of Health-System Pharmacists Guidelines on handling hazardous drugs1990199519991976197920042006NIOSH Alert Preventing occupational exposure to antineoplastic and other HDs in healthcare settings2007DHHS NIOSH “Medical Surveillance for health care workers exposed to HDs”Source: Massoomi, 2007
65 Environmental Monitoring HOT TOPICS IN CHEMOTHERAPY 2011Environmental MonitoringWARNING: Working with or near hazardous drugs in healthcare settings may cause:Skin rashesInfertilityMiscarriageBirth defectsPossibly leukemia or other cancersTHERE IS NO SHORTAGE OF GUIDELINES. They have been arount a LONG TIME …Have you examined your work practice and identified risks of exposure to HDs?Environmental monitoring and Medical Surveillance
66 HOT TOPICS IN CHEMOTHERAPY 2011 Perhaps, when we are fully aware of the potential danger… we will be better able to “Control” survival?It is estimated that 5.5 million health care workers are potentially exposed to hazardous drugs or drug waste at their worksites.American Journal of Nursing. November 2010.Volume 110, No.11, pg. 20Environmental monitoring and Medical Surveillance
67 Environmental Monitoring HOT TOPICS IN CHEMOTHERAPY 2011Environmental MonitoringOver the years environmental monitoring has continued to reflect challenging organizational issues.Tom Connor, a research biologist with NIOSH, studied surface contamination in 1999 and 2010, with similar results of widespread contamination on countertops, carts, trays and surfaces where IV bags were placed.75 % of wipe samples were positive in drug preparation area65% of wipe samples were positive in drug administration areasOften, because the side effects are not acute, personnel have a reduced perception of the risk. Many deny the potential problem.ALWAYS BE COMPETENT … NEVER BE “COMFORTABLE.”Environmental monitoring and Medical Surveillance
68 Environmental Monitoring HOT TOPICS IN CHEMOTHERAPY 2011Environmental MonitoringMonitoring studies are now even more sophisticated, addressing cytogenetics: chromosomes 5, 7, and 11, which are signature markers for therapy related MDS and AML.Melissa McDiarmid, Professor and Director of Occupational Health Program at the University of Maryland School of Medicine states, “Recognition of the hazard is lagging behind the science. We haven’t caught up with this yet.”In her study of 63 healthy volunteers from three university hospitals, more chromosomal damage was found in participants who had been exposed and experienced increased events with handling chemotherapy. Please know that these individuals work routinely with chemotherapy and state that they follow NIOSH Guidelines.“Chromosome 5 and 7 Abnormalities in Oncology Personnel Handling Anticancer Drugs.” Journal of Occupational & Environmental Medicine. Volume 52, Number 10, October 2010, Pages 1028 – 1034.These findings raise questions regarding individual and/or facility compliance with safe-handling guidelines, Institutions MUST effectively monitor and ensure work practices are consistent with NIOSH recommendations and provide up to date education regarding exposure risk.Environmental monitoring and Medical Surveillance
69 HOT TOPICS IN CHEMOTHERAPY 2011 ARE WE “OUT OF CONTROL?”Occupational Safety and Health Administration (OSHA) indicates that safe levels of occupational exposure to hazardous agents cannot be determined and there is no reliable method of monitoring work-related exposure. Therefore, it is vital that those who work with HDs are adherent to standards of practice (SOP) designed to minimize occupational exposure.CHAMPION the “ALARA” approach to handling and preparing drugs. That is, “as low as reasonably achievable.”Environmental monitoring and Medical Surveillance
71 State of Washington: Senate Bills 5149 and 5594 Passed 2011, Regular Session of 62nd Legislature Legislature declared that health care personnel who work with or near hazardous drugs are provided with appropriate regulation of the handling of hazardous drugs, regardless of setting, to protect health care personnel from exposureAn ACT requiring the department of health to collect current and past employment information in the cancer registry programThis legislation was spearheaded / supported by Seth Eisenberg, a pastChemotherapy SIG Coordinator and current SIG Webmaster, in response to thedeath of Sue Crump, a hospital pharmacist, who died from pancreatic cancerafter 23 years of mixing chemotherapy agents and years of toxic exposure.
72 Medical Screening / Surveillance HOT TOPICS IN CHEMOTHERAPY 2011Medical Screening / SurveillanceMedical Screening is, in essence, only one component of a comprehensive medical surveillance program. It has a Clinical Focus on early diagnosis and treatment.Medical Surveillance is to detect and eliminate any underlying causes, such as hazards or exposures of any trends, thus a Prevention Focus.Environmental monitoring and Medical Surveillance
73 OSHA Recommendations for Medical Surveillance * For detection and control of work-related health effects, job-specific medical evaluations should be performed as follows:Prior to job placementPeriodically during employmentFollowing acute exposuresAt time of termination or transfer (exit exam)* The concept of a Medical Surveillance Program is only a NIOSH and OSHA recommendation and is not mandated.Environmental monitoring and Medical Surveillance
74 Elements of a Medical Surveillance Program for HDs should include: HOT TOPICS IN CHEMOTHERAPY 2011Elements of a Medical Surveillance Program for HDs should include:Reproductive and general health questionnaires completed at time of hire and periodically thereafterLaboratory work, including CBC and urinalysis completed at time of hire and periodically thereafter. (LFT and transaminase tests may also be considered)Physical examination completed at time of hire and as needed when health questionnaire or blood work indicates abnormal findingsFollow-up for workers who have shown health changes or who have had significant exposure to HD.Track trends with questionnaires and sick-callsEnvironmental monitoring and Medical Surveillance
75 Nebraska Methodist Hospital (NMH) HOT TOPICS IN CHEMOTHERAPY 2011Nebraska Methodist Hospital (NMH)Has established a 4-tier formal Surveillance Program for Hazardous Drugs, including:Self-SurveillanceEmployer/Supervisor SurveillanceComprehensive Medical SurveillancePost-Exposure Surveillance (known or suspected), April 2008Environmental monitoring and Medical Surveillance
76 Many Institutions Starting to Support Medical Surveillance HOT TOPICS IN CHEMOTHERAPY 2011Many Institutions Starting to Support Medical SurveillanceNebraska Methodist HospitalIntermountain Healthcare, UtahDuke University, North CarolinaStanford University, CaliforniaColumbia UniversityEnvironmental monitoring and Medical Surveillance
77 Employee Health and Well-Being HOT TOPICS IN CHEMOTHERAPY 2011Employee Health and Well-BeingThe topic of Medical Surveillance has been discussed for many years among comprehensive cancer centers.“We depend on meticulous engineering controls, such as PhaSeal closed system and use of PPE, such as chemotherapy gowns, gloves and goggles … With these precautions there should not be any significant exposure.”“There is no scientific evidence to show that routine laboratory testing is of use in detecting potential health effects from handling and administration of hazardous drugs.”“In event of accidental exposure due to tubing disconnection or faulty equipment, Employee Health and Well-Being should be notified immediately. Exposure follow-up is handled on a case by case basis.” Elizabeth Hudson,MSN, RN, FNP-BC, CCM, COHN-SEmployee Health and Well-Being at MDACCEnvironmental monitoring and Medical Surveillance
78 Nebraska Methodist Hospital (NMH) HOT TOPICS IN CHEMOTHERAPY 2011Nebraska Methodist Hospital (NMH)Conclusions:“…costs associated with protecting health care workers from exposure to hazardous chemicals is incalculable, in terms of mortality and morbidity of health care personnel.”“We do not fully understand the magnitude of hospital personnel’s continuous exposure to HDs, but because we are aware of the potential for risk, it is our obligation to prevent harm to our employees.”, April 2008Environmental monitoring and Medical Surveillance
79 Administrative Controls HOT TOPICS IN CHEMOTHERAPY 2011National Institute for Occupational Safety and Health (NIOSH) Recommends Primary Prevention to ProtectEngineering ControlsBiological Safety Cabinets (BSC)Compounding aseptic containment isolatorsClosed System Transfer Devices (CSTD)Needleless systemsLuer-Lock connectorsAdministrative ControlsManagement Policies / ProceduresEducation and TrainingMedical Surveillance (Form of secondary prevention)Personal Protective Equipment (PPE)Environmental monitoring and Medical Surveillance
80 HOT TOPICS IN CHEMOTHERAPY 2011 SummaryLeave today INSPIRED to work on a “Control Plan” regarding Environment Monitoring and Medical Surveillance for Hazardous Agents at your institution.”Environmental monitoring and Medical Surveillance
81 Questions/Comments/Discussion Microsoft Engineering ExcellenceQuestions/Comments/DiscussionHOT TOPICS IN CHEMOTHERAPY 2011Please plan to attend our follow-upRound Table SessionTODAY ( 2:30 pm – 4:00 pm )Ballroom HMicrosoft Confidential