Presentation on theme: "Side effects of Chemotherapy"— Presentation transcript:
1 Side effects of Chemotherapy Dr G SrinivasanLocum Cons OncologistBroomfield HospitalChelmsford
2 From inability to let well alone; from too much zeal for the new and contempt for what is old;from putting knowledge before wisdom, science before art, andcleverness before common sense;from treating patients as cases;and from making the cure of the disease more grievous than theendurance of the same, Good Lord, deliver us.Sir Robert Hutchison MD FRCP ( )
3 Paul EhrlichNobel Prize 1908, Medicine &PhysiologyFather of Chemotherapy
4 Serendipity Serendipity Chemical warfare - World War I 2nd December 1943105 German bombers – attacked 27 Allied ships in Bari Harbour‘John Harvey’ shells of mustard gasLouis Goodman & Alfred Gilman – injected Nitrogen mustard into patient with Hodgkin’s Lymphoma- 1942SerendipitySerendipity
5 Adapted from History of Cancer Chemotherapy, Cancer Research Nov 1 2008, 68, 8643
6 Adapted from History of Cancer Chemotherapy, Cancer Research Nov 1 2008, 68, 8643
16 ManagementPreventionTo be given within 6 hours – day 1, 2 and 3 ( £7000)Quick recognition – stop infusionCold packsDexrazoxane (Savene) – originally used to prevent cardiotoxicity ofanthracyclinesFe + anthracyclines → Oxygen free radicalsHyaluronidase infiltration - Vinca alkaloids, taxanesDimethyl sulfoxide (DMSO) – topical solvent
17 Assessment of VeinsRecognise need for central lines – PICC, Hickman, PortacathNational Extravasation Information Service, St Chad’s Unit, City Hospital, BirminghamGoolsby TV, Lombardo EA (2006) Extravasation of chemotherapeutic agents:Prevention and treatment. Semin.Oncol. 33,Over compliance
18 Chemotherapy Induced Nausea & Vomiting CINVVomiting CentreChemoreceptor Trigger Zone (CTZ) / Area Postrema (base of IV ventricle)Outside blood brain barrierReceptors – Dopamine D2, serotonin 5 HT-3, opioid, acetylcholine, Subst PAcute emesis - < 24 hoursDelayed emesis - > 24 hoursAnticipatory emesis – before chemotherapy
26 Haematological toxicity Marrow suppression - cytotoxicDepends onDrugs – single agent / combinationDoseSchedule - eg., 14 day CHOP vs 21 day CHOPPatient factor – bone mets, radiation, age, previous chemotherapy,3rd space collections
27 Neutropenia< 1.5 x 10⁹/ LFebrile (Temp > 37.5 C) + neutropeniaNeutropenic Sepsis – vasodilation, hypotension, end organ failureLow riskFit patient, no extremes of ageRegime not very marrow suppressiveNeutropenia not expected to be prolongedNo systemic symptomsSomeone at home, access to telephone, hospitalHigh riskMyelotoxic regimes – eg., lymphoma, leukaemiaImmunosuppression – HIV,
28 Awareness and AccessPatient / staff education24/7 access to specialist care , Acute Oncology ServiceOral antibiotics – Ciprofloxacin 750 mg bd + Co-amoxiclav 625 mg tds x 7 daysClarithromycin if allergic to PenicillinAdmission – do not wait for investigation resultPiperacillin IV 4.5 g tds + Gentamicin 6mg/Kg loading dose hrs, if afebrile 24 hrsmore followed by oral AntiBx for 5 daysTeicoplanin if allergic to PenicillinConsider removing central line if fever does not subside in hrsConsider Teicoplanin, antifungalsFollow local protocols, microbiology advice
30 Role for Prophylactic AntiBx Significant Trial - Quniolone AntiBx vs Placebo – small but definite roleProphylactic Septrin – for lymphomasAnaemiaRed cell transfusions – to improve quality of lifeErythropoietin – not routinely recommended, under NICE reviewThrombocytopaenia – Platinum compounds, bone marrow infiltration
31 MucositisStomatitisCould be isolated or part of neutropeniaHead & Neck radiotherapyMeticulous oral hygeine, rinses, anti thrush, analgesicsDiarrhoeaFlouropyrimidines, Irinotecan, small molecule targeted agentsSunitinib, Sorefanib, Erlotinib, GefitinibHydration, loperamide, severe cases Octreotide infusionDihydropyrimidine dehyrdrogenase (DPD) deficiency ~ 5 % of Caucasians
37 Cancer patient vs Cancer Survivor 58% of long term survivors of childhood cancer suffer one ongoing medicalproblem; 32% have two or more41% Endocrine disorder26% organ toxicity17% impaired mobility15% Neuropsychological14% infertility13% Sensory deficits10% Cosmetic problemsSecond cancersGonadal dysfunction(Stevens et al, Eur J Cancer, 1998)
38 Hormonal Therapies Breast cancer Tamoxifen – (SERM) - hot flushes, thrombosis, ↑endometrial cancers,visual problemsFulvestrant (ER antagonist)AnastrazoleLetrozole(Non steroidal aromatase inhibitor) - arthralgia, osteoporosisExemestane (steroidal AI)LHRH agonist implants
40 Nephro toxcity Cisplatin (also Ototoxcity) Assess Renal function including GFRCarboplatin- less nephrotoxicEDTA, 24 hour Creatinine clearanceF x (140- age in yrs) x weight (kg)Cockcroft- Gault formulaCrcl =Serum Creatinine (mmol/L)(GFR)F = 1.04 (females); 1.23 (males)Calvert’s formulaDose (mg) = desired AUC x (GFR + 25)AUC – Area under the curveAUC 8 for adjuvant Germ cell tumoursUsually 5 or 6
47 mTOR InhibitorsMammalian Target of RapamaycinRapamycin and RapaloguesTemsirolimusEverolimusHyperglycemia – due to ↑ gluconeogenesis ↓ peripheral gluc uptakeDyslipidemiaLung injury, mucositis, rash
48 £££ Big side effect Cetuximab – 8 wks - £20,000 Ipilimumab for melanoma - £ 20,000 per dose x 4Cancer Drug FundNICE
49 Professor Jane Maher, of Macmillan Cancer Support This report provides very disturbing information about the safety of treatment for incurable cancer Professor Jane Maher, of Macmillan Cancer SupportThis report provides very disturbing information about the safety of treatment for incurable cancer Professor Jane Maher, of Macmillan Cancer SupportProfessor Jane Maher, of Macmillan Cancer SupportThis report provides very disturbing information about the safety of treatment for incurable cancer Chemotherapy | National Cancer Action TeamThe National Cancer Action Team are leading a number of work streams to ensure that the recommendations of the NCAG report and the Cancer Reform ...Doctors 'rely on chemo too much'BBC NewsSome 80,000 patients undergo chemotherapy each yearDoctors are being urged to re-think their approach to giving chemotherapy during care at the end of life.A review of 600 cancer patients who died within 30 days of treatment found that in more than a quarter of cases it actually hastened or caused death.Professor Jane Maher, chief medical officer at Macmillan Cancer Support, said: "This report provides very disturbing information about the safety of treatment for incurable cancer.The report by the National Confidential Enquiry into Patient Outcome and Death said doctors should consider reducing doses or not using chemotherapy at all.
50 Cancer patients face the prospect of longer waits for chemotherapy because units are being “stretched to the limit” by ever-increasing demand, say specialists.Chemotherapy units 'stretched to the limit'Daily Telegraph, 7th July 2013BreachCancer waiting timesPatient / relatives demandsTargetsAlso, patients or their families may demand chemotherapy regardless of the patient's prognosis,
52 70 yr manCancer ascending colon – R hemicolectomyMultiple liver metastases – Mar 2013Current Rx – Palliative Oxaliplatin/ Capecitabine/ BevacizumabName the main side effect from OxaliplatinThe man complains of profuse diarrhoea – what could be responsible?Which agent is the targeted RX? What does it target? What will you monitor?He develops a massive PE – what could be responsible?
53 This man’s liver metastases progresses. He is KRAS wild type You commence him on a combination ofIrinotecan/ infusional 5 FU/ CetuximabWhat drug would you give as pre treatment before Irinotecan?Patient seeks advice for extensive skin rash/ acne – which agent isresponsible?
55 SummaryCancer incidence and people diagnosed with it is increasingMore patients and elderly patients are being treatedCancer treatment is advancing rapidlyLong term survival seen in some tumour typesMore and more combination treatmentsMore and unique side effectsLong term consequences of cancer therapy
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