<prompt> Most important adverse effect of Bleomycin is?MyelosuppressionHeaptotoxicityPulmonary fibrosisPeripheral neuropathy  <response>: ANSWER: C Pulmonary fibrosisREF: KDT 6 b edition page No: 827, Harrison 17th ed chapter 81See APPENDIX-37 below for CLASSIFICATION OF CANCER CHEMOTHERAPY AGENTSThe most feared and most common complication of bleomycin treatment is pulmonary fibrosis, which increases in incidence at 300 cumulative units administered and is minimally responsive to treatment e.g., glucocorticoids.The most common early symptoms of bleomycin-induced pulmonary toxicity are cough and dyspneaThe earliest indicator of an adverse effect is a decline in the DLCO, although cessation of drug immediately upon documentation of a decrease in DLCO may not prevent further decline in pulmonary function.Risk factors of developing Bleomycin induced pulmonary fibrosis are:Elderly patientsCo existing lung diseasePrevious radiation therapyHigh doses of bleomycin 150mgm2 APPENDIX - 37Classification of Cancer Chemotherapy Agents:GroupSubgroups AgentsAcute ToxicityDelayed ToxicityUsesAlkylatingAgentsNitrogen Mustard Alkylation of DNA at N7 06 position of Guanine -DNA crosslinking I; bn 2 strands - prevents duplication1 MechiorethamineFirst anticancer drugCINV-chemo induced nausea vomiting 4hr- 48hrsMyelosuppressionMyelosuppression delayed type-onset 7d, Nadir 10-14d, recorerv 21-28dAlopeciaMOPP-HodgkinslymphomaAA are commonly used in chronic leukemia2 Cyclophosphamide1CP - 4hydroxyCP -aldophosphamide- Acrolein toxic phosphamide mustard activeCINVMyelosuppressionCPIfoMyelosuppression CPIfo Alopecia, SIADHHemorrhagic cystitis IfoCPSec cancer-transitional cell cancer of bladderWagnersgranulomatosis DOC CMF-Breast, small cell lung ca Broad spectrumAA are nonphase specific3 Ifosfamide 4hydroxy ifosfamide activeCINVMyelosuppressionCPIfoMyelosuppressionCPIfoAlopeciaHemorrhagic cystitis IfoCPBroad spectrum Lung, breast, ovary, sarcoma, testis, germ cell tumorAA causes secondary leukemia in 4-5 years4 Melphanamino acid derivative ofmechloretamineCINVMyelosuppressionMyelosuppression No alopeciaMultiple myeloma DOCCan replace C in CMF 5 ChlorambucilMyelosuppression CINV is rareMyelosuppression No alopeciaCLL, Hodgkins Nitrosoureaslipophilic-crosses BBB Nitrosoureas causes delayedMyelosuppression onset-15d, Nadir-4wks, recovery-6wks 1 Carmustine BCNU- bis chloro nitroso ureaCINV severe-2hrsMyelosuppression, male infertility,Pulmonary fibrosisBrain tumors DOCGlioblastomamultiforme.Astrocytoma,Medulloblastoma 2 Lomustine CCNUCINV severe-2hrsMyelosuppression Interstitial lung diseasedo 3 Semustine methyl CCNUCINV severe-2hrsMyelosuppressiondo 4 Streptozocin methylation of protein nucleic acidCINV severe-2 hrsNo MyelosuppressionPancreatic islet cell tumorCarcinoid tumor Alkyl SulfonatesIntra strand cross linking of DNA by 2 N7 Guanine BUSULFAN Dealkylating agentHyperuricemiaMCSterility, gynecomastia, seizures, Skin pigmentation, Adrenal insufficiency Pulmonary fibrosis specificCM L-DOC until imatinibConditioning of BM transplant Ethyl Enimines ThiotepaOrganophosphorousCINVMyelosuppressionSeldom used nowNon ClassicalAlkylatingAgentsTriazenes Acts on RNA Protein synthesis not mild DNADacarbazine Active- methyl carbonium ionCINV-severePermanent sterility Myelos uppre ssion earlyclassicalMAID-sarcoma, ABVD-Hodgkins Malignant melanoma most active agent Procarbazine autoxidize spontaneously, Active- Azoprocarbazine, crosses BBBCINV, MAO inhibitor Disulfiram like reactionMyelosuppression,DermatitisLeukenogenic,teratogenicMOPP-HodgkinsPCV-Glioblastoma AltretamineCINV-severe HypotensionNeuro toxic NephrotoxicRefractory ovarian cancerAlkylating Like AgentsPlatinum Compounds 1st gen platinum Inactivated by aluminumCisplatinCINV most emitogenicHypo Mg, K, Ca sec to hypo MgMyelosuppression N ephrotoxicity, Ototoxicity Secondary leukemiaCMF-Solidmalignancies2nc generation platinum, Cross resistance- cisplatinCarboplatinCINV ciscarboMyelosuppressioncarbodsNo nephrotoxicityLess potent than cisplatin 1:4 GemCarco-Iung cancer3rd generation platinum No cross resistanceOxaliplatinPSN pathy reversible hand foot, temp lossNeurotoxicity dose limitingNo nephrotoxicity PSN pathyflrreversible, hand, foot, leg, arm, temp loss, propio lossFOLFOX- colon cancerCiscarboplatin resistance AntimetabolitesFolate Antagonists S phase specificMethotrexate HepatotoxicityMyelosuppressionMucositisChoriocarcinoma DOC, ALL, Osteosarcoma. RA, ectopic Myasthenia, psoriasis, meningeal leukemia intrathecal routeInhibits DMA syn thesisPemetrexed : Mesothelioma, nonsmall cell lungNo acute toxicidesPurine Analogue Commonly used in acute leukemias6 THIO Guanine MyelosuppressionHepatotoxicityAdult acute leukemia 6 Mercapto Purine Myelosupp ression, hepatotoxicityChildhood acute leukemia Fludrabine Myelosuppression, Flu like symptom fever, myalgia, arthralgia Cladribine Myelosuppression, Nephrotoxic, ClXVHairy cell leukemia Pentostatin NephrotoxicHairy cell leukemia Pyrimidine Analogue 5 Fluorouracil 5-FU GI upset-diarrhea MC Hand foot syndrome, CINVMyelosuppression, neurotoxicity Cerebellar ataxia Cytrabine Stomatitis, CINV, Cerebellar ataxia MyelosuppressionAML Capecitabine CINV, Diarrhea, Hand foot syndrome Myelosupp ression 5FUMetastatic breast cancer, Metastatic colorectal cancer Gamecitabine CINV, Myelosuppression dose limitingPancreatic cancer DOC Bladder Nonsmall cell lung CaAntibioticsAnthracyclinsTopoisomerase 2 inhibitor meQuinone Free radical injury intercalation bn DNA strandsMembrane binding responsible for cardiotoxicity Doxorubicin AdriamycinCINV, AlopeciaMyelosuppression dose limiting, neutropenia th rombocytopenia Cardiotoxicitycardiomy opathy, CHFRadiation recall Hand foot syndromeBroad spectrum Solid tumors sarcomas rhabdo leiomyosarcoma, Kaposi sarcoma DaunorubcinCl MV, AlopeciaMyelosuppression, cardiotoxicity, radiation recallNarrow spectrum AML Idarubcin synthetic Daunorubicin analogueCINV, Alopecia, Red urine not hematuriaMyelosuppression, cardiotoxicity, radiation recallAML more efficacious than daunorubicin MitoxantroneCINV, Bluish discoloration of nailsMyelosuppression dose limitingLower cardiotoxicity? Other Antibiotics BleomycinGlyco peptide Antibiotic Free radical injury - ds- ss DMA breaks, have both DNA Fe binding domainAllergic reaction HypotensionPulmonary fibrosis dose limitingMucocutaneous toxicity? Marrow sparingHL, NHL, SCC Malignant pleural effusionAscitis sclerosing agent Mitomycin- CActs as alkylating agentCINVHemolytic uremic syndrome. Pulmonary- fibrosis, 8th nerve damageRadiosensitizer- DOC, SCC Dactinomycin Inhibits all forms of DMA dependent RMA synthesis, r-RNA most sensitiveCINVMyelosupp ression Alopecia Radiation recallPediatric tumors Ewings, witms, Rhabdomyosarcoma Radiosensitizer ActinomycinCINVDesquamationMyelosuppressionAlopeciaPediatric tumors Ewings, wilms, Rhab domyosarcoma Radiosensitizer PlicamycinCINV EnzymeL-ASPARGINASE inhibits protein synthesis of tumor cell by depletion of L-AspargineAnaphylaxis hyper sensitivity- fever, chills, rash, urticaria brochospasm, hypotension if severeHypercoagulable state Pancreatitis, Hepatotoxicity Marrow sparing, no alopeciaALLIneffective in solid tumorsnormal cells sparedPlant DerivedVinca AlkaloidsM phase specificInhibits tubulin polymerizationMitotic inhibitors VincristineAlopeciaPSNpathySIADH, Marrow sparingLymphosarcoma, wilms, Ewings Remission of childhood acute leukemia. VinblastineAlopecia Vc VbPSNpathy Vc Vb MyelosuppressionHodgkin s, testicular carcinoma EpipodophylotoxinsTopoisomerase 2 inhibitor Etopside VP-16CINV, HypotensionMyelosuppression, early onset secondary leukemia 1-3 years alopecia Teniposide VP-26 TaxansM phase specificEnhance tubulin polymerizationSpindle poison PaclitaxelHypersensitivityPSNpathy stocking glove type Myelosuppression,Cisplatin resistance Relapse resistant breastovary ca Docetaxel more potentHypersensitivityMyelosuppression, PSNpathy is less frequentCisplatin resistance, Relapse-resistant brovary ca CamptothecinTopoisomerase 1 inhibitorss DNA breaks TopothecanCINVMyelosuppression dose limiting Irinothecan active SN-38CINV, Cholinergic syndrome SLUDGE including early diarrhea-24hrsMyelosuppression, cholinergic syndrome SLUDGE including late diarrhea 3-10d dose limitingAdvanced colorectal ca- DOCMiscellaneousArsenic Trioxide degradation of PM LI RARa proteinHeadache, lightheadednessCINVCardiotoxicity QT prolongation, arrhythmias, Myelosuppression Syndrome-fever, fluid retention, wt gain, rashAPL-induction in tretinoin relapse and refractoryHydroxyurea has 100 oral bioavailabilityHydroxyurea inhibits ribonucleotide reductase - inhibits DMA synthesisCINVMyelosuppression dose limitingHyperpigmentationCMLAML-blast crisis Imatinib Bcr-Abl Tyrosine kinase inhibitorCINVFluid retention, Ankle perioral edemaCML-chronic phase GIST with Ckit tyrosine kinase Dasatinib Nilotinib novel agents- TK inhibitors CML- imatinibresistanceintoleranceAnticancer Drug Toxicities:MYELOSUPPRESSIONAll except Asparginase, Vincristine, BleomycinCARDIOTONICAnthracyclins, arsenic trioxideNEPHROTOXICPlatinum compounds cisplatincarboplatinoxaliplatinPULMONARY FIBROSISBleomycin. Busulfan, CarmustinePERIPHERAL NEUROPATHYGxaliplatin, vincristine Taxans stoking glove typeHAEMORRHAGIC CYSTITISCyclophosphamide, IfosfamideHAND FOOT SYNDROME5FU, Capecitabine, DoxorubicinCEREBELLAR ATAXIAPyrimidine analogs like Cytrabine 5FUSIADHCyclophosphamide, VincristineSECONDARY LEUKEMIAAll alkylating agents alkylating like agents in 4-5 years E topside in 1-3 yearsSTERLITYAlkylating agentsDISULFIRAM LIKE REACTIONProcarbazineCHOLINERGIC SYNDROMEIrinitecanRADIATION RECALL SYNDROMEAnthracydinsAnticancer Drugs Toxic Amelioration:ToxicityMeasuresMethotrexateFolinic acidAlkalization of urine Mtz is weak acid reabsorbed in acidic urineHemorrhagic cystitis cyclophosphamide, ifosfamideME SNA 2 mercapto ethyl sulfonyl sodium systemic ACETYLCYSTEINE irrigation of bladderHigh fluid intakeFrequent voidingCINV Cytotoxic drug induced nausea Stvomiting Ondansetron 5HT3 AntagonistCytotoxic drug induced MucositisPabfermin human recombinant keratinocyte growth factorTUMOR LYSIS SYNDROME hyperkalemia, hypophosphatemia, hyperuricemia, hypemricosuria, hypocalcaemia, acute renal failureprophylactic ALLOPURINOL xanthine oxidase inhibitoralternatively RASBURICASE urkaseAggressive hydrationHigh urine outputAlkalization of urine not recommendedcontroversialDiuresis is reserved for well hydrated patientsHEMODIALYSIS if above fails MYE LOS OPPRESSIONFor AnemiaERYTHROPOIETIN recombinantFor NeutropeniaFILGRASTIM- Granulocyte colony-stimulating factor G-CSF analogSARGRAMOSTTM - Recombinant granulocyte macrophage colony stimulating factor GM-CSFFor ThrombocytopeniaOPRELVEKIN IL-11BONE MARROW TRANSPLANT for extreme suppressionCANCER CACHEXIATHALIDOMIDECYTOPROTECTION of normal tissueAMIFOSTINE WTR-2721prodrugactive free thiolWR-1065. activation normal tissueUSEScispIatin based chemotherapy radiation therapyAnthracyclins induced CARDIOTOXICITYDEXRAZOXAXE ICRF-187 Iron chelating agent Cardio protective agent, derivative of EDTA 