Cancer Drug Table 2024 PDF

PHRM311 Oncology - Drug Lists Dr. Judy Wong Cell Cycle Specific Agents Drug Mechanism of Activation Pharmcokinetics Toxicities Resistance Notes...

PHRM311 Oncology - Drug Lists Dr. Judy Wong Cell Cycle Specific Agents Drug Mechanism of Activation Pharmcokinetics Toxicities Resistance Notes Action Anti-metabolite: Folate analogs Methotrexate Inhibition of Parent drug and Well absorbed GI disturbances. 1. Impaired Folinic acid dihydrofolate metabolite orally, also Myelosuppression cellular uptake rescue allow Rheumatrexâ reductase, inhibit competitively bind administered IV Nephropathy lethal dose of the generation of to DHFR and IT. 50% Teratogenic 2. DHFR MTX be used tetrahydrofolate plasma protein Pulmonary toxicity mutation or in aggressive and downstream binding. Excreted gene chemo- purine and thymine principally by the High amplification therapy synthesis. kidney. emetogenicity is dose-related 3. Increase Activity is S-phase MRP drug specific export Leucovorin 1. protection of Rapidly converted Orally absorbed. Toxicity mainly (Folinic Acids) normal cells in into 5- Excretion through related to the co- high dose MTX methyltetrahydrofol renal elimination administered Wellcovorin â therapy ate derivatives in compounds the intestine 2. synergistic with Non-emetogenic 5-FU to increase formation of TS- 5dUMP-MTHR ternary complex. Raltitrexed Competitive Polyglutamated by IV infusion. GI disturbances. 1. Increase TS inhibition of cellular Myelosuppression levels Tomudex â thymidylate folylpolyglutamate Hepatic 2.Decrease synthase synthase (FPGS). disturbances are poly- Polyglutamation rare but could be glutamation Activity is S-phase increase the binding fatal specific affinity of 3.Impaired Raltitrexed to TS. Low to moderate intra-cellular emetogenicity uptake Page 1 of 13 PHRM311 Oncology - Drug Lists Dr. Judy Wong Anti-Metabolites: pyrimidine analogs Fluorouracil Inhibits DNA Activated in target Variable oral GI disturbances 1. Decreased Active drug is (5-FU) synthesis by (tumor) cells to absorption. Myelosuppression level of metabolized inhibiting FdUMP by various Usually Cardio-toxicity thymidylate by dihydro- Adrucil â thymidine metabolic pathways administered IP or Palmar-plantar synthase pyrimidine Fluoroplex â synthesis. IV (bolus, erythro- (target) dehydro- FdUMP forms a infusions). 80% dysesthesia genase (DPD) ternary complex catabolized by liver 2. Decreased to inactive with thymidylate and excreted as Rarely emetogenic concentration metabolites. synthase and respiratory CO2. Mild nausea and of MTHF Deficiency of methylene vomiting. (cofactor for DPD cause tetrahydrofolate ternary severe Capecitabine Metabolized to Oral administration, complex) toxicities. Activity is S-phase 5’deoxy-5- recommended after Xeloda â specific fluorocytidine in food. 3. increase liver, and activated Capecitabine is an expression of to FdUMP in target orally available anti-apoptotic cells prodrug of 5-FU proteins Cytarabine As an analog to Activated Low oral Cerebellar toxicity 1. Increased (Cytosine cytidine, Ara-C is intracellularly to bioavailability. IV, Myelosuppression metabolism by Arabinoside, incorporated into cytosine SC and IT Ocular toxicity cytidine Ara-C) DNA. arabinoside administered. Pulmonary edema deaminase Incorporation triphosphate Rapid and Fever, Flu-like Cytosar â causes chain extensively symptoms 2. decreased termination. Also metabolized by import of inhibits DNA cytidine deaminase High drugs polymerase in to inactive emetogenicity is replication and metabolites. dose-related 3. increase repair functions Excretion of Ara-C survival and metabolite pathway Activity is S-phase chiefly through proteins specific renal elimination expression Page 2 of 13 PHRM311 Oncology - Drug Lists Dr. Judy Wong Gemcitabine Analog to cytidine, Activated IV infusion. Rapid Myelosuppression see above for Gemzar is intracellularly to and extensively Hemolytic uremic Ara-C Gemzar â incorporated into dFdCTP metabolized by syndrome DNA. cytidine deaminase Pulmonary toxicity Incorporation to inactive is rare but could be causes chain metabolites. severe. termination. Also Elevated hepatic inhibits DNA Elimination mainly enzyme with polymerase in through renal unclear clinical replication and clearance. significance. repair functions Low to moderate Activity is S-phase emetogenicity specific Topoisomerases Enzyme Inhibitors Irinotecan Inhibition of Prodrug, activate IV infusion, GI , life- 1. Over- UGT enzyme Topoisomerase I by irinotecan is rapidly threatening expression of (glucuronidat Camptosar â Carboxy-esterase converted to its diarrhea. MRP drug ion) poly- Cytotoxicity is S- active metabolite Cholinergic efflux pump. morphism phase specific SN-38. Syndrome determines Both parent drug induced 2. mutations in the clinical and SN-38 are abdominal pain. Topo I use of highly protein- irinotecan bound. Myelosuppression 3. Increased Hepatic metabolism DNA repair by CYP3A and the activities glucuronidation of High-moderate SN-38 are clinically emetogenicity important. Page 3 of 13 PHRM311 Oncology - Drug Lists Dr. Judy Wong Etoposide Inhibition of Oral or IV Myelosuppression 1. P- Secondary Topoisomerase II (preferred). Congested heart glycoprotein leukemia due Vepesid â by formation of a 40% of failure/myocardial over- to drug Etopophos â ternary complex administered dose infarction expression treatment seen between Topo II, is excreted intact. in childhood drug and DNA. Extensively bound Induces Type I 2. mutation or acute lympho- to plasma proteins. Hypersensitivity reduced blastic Activity is S and Reduction in serum Reactions expression of leukemia G2 phase specific. albumin will Topo II (ALL) increase toxicities Low to moderate patients of etoposide. emetogenicity 3. mutation or loss of function of p53 Microtubule Inhibitors Vinblastine Bind to specific IV infusion. Myelosuppression 1. Increase Vinblastine is site of b-tubulin, Variable plasma GI disturbances expression of lethal if Velbe â preventing the protein binding. Peripheral P-glycoprotein injected IT polymerizaton of Drug is excreted in neuropathy and/or the tubulins to form both urine and Brochospasm MRP drug microtubule. feces. Tissue necrosis due efflux pumps to extravasation Cells are arrested 2. mutations in in mitosis. rarely emetogenic b-tubulin binding sites Vincristine Activity specific IV infusion. Neurotoxicity. Vincristine is for M-phase Vincristine is Peripheral lethal if Oncovin â metabolized by neuropathy. injected IT Vincasar â CYP3A and alopecia excreted primarily Myelosuppression in feces less common than in vinblastine non-emetogenic Page 4 of 13 PHRM311 Oncology - Drug Lists Dr. Judy Wong Paclitaxel Binds to b-tubulin Not absorbed Myelosuppression 1. Increased Severe hyper- and promote the orally. Administer Peripheral expression of sensitivity to Taxol â stability of by IV infusion, or neuropathy P-glycoprotein paclitaxel microtubule by IP. Hepatic could be polymers. Cells metabolism Hypersensitivity 2. Mutations in minimized by are arrested in (CYP2C8) and Reactions b-tubulin pretreatment metaphase of biliary secretion with cortico- mitosis. account for CVS toxicity: 3. increase steroid majority of Bradycardia and expression of Activity is specific elimination hypotension survivin, an for M-phase anti-apoptotic Low-moderate factor emetogenicity Docetaxel Higher affinity to Administer by IV Myelosuppression Wide inter- b-tubulin than infusion. Pulmonary patient Taxotere â paclitaxel. Clearance by toxicity variability Stabilized CYPA4/5. due to microtubule Excretion through Less incidences of CYP3A4 formation, arrested biliary/fecal hypersensitivity poly- cells in mitosis. elimination than paclitaxel morphism Activity is M- Low emetogenicity phase specific Genotoxic Agents Drug Mechanism of Action Activation Pharmacokinetics Toxicities Resistance Notes Alkylating Agents: Nitrogen Mustards Cyclophosphamide Alkylation of Prodrug, Absorption: Bone marrow, 1. increased Inter- nucleophilic activated oral or IV neurotoxicity glutathione patient Cytoxanâ moieties on DNA by mucosal, GI , conjugation variability Procytoxâ and protein CYP2B6 Elimination: genitourinary tract of hepatic epithelium, hair 2. increased activation metabolism follicles metabolism by Page 5 of 13 PHRM311 Oncology - Drug Lists Dr. Judy Wong (CY3A4, ADH, Cardio-toxicity at aldehyde and GSH and others), high doses dehydrogenase toxicity half-life of parent Hemorrhagic drug ~7hours cystitis can be 3. increase Secondary relieved by DNA repair by urinary High coadministration MGMT bladder emetogenicity is of mesna and dose related hemato- logical cancers Ifosfamide Oxazophosphorine Prodrug, Administered Bone marrow, 1. increased different alkylating agent. activation by oral or IV neurotoxicity, glutathione pharmaco- Ifex â Ifosfamide in the liver infusion. urotoxicity and conjugation kinetics interferes with DNA by hepatic Elimination: nephro-toxicity parameters metabolism through enzyme, renal (up to 50% hemorrhagic 2. increased from formation of DNA- mainly unchanged drug) cystitis metabolism by cyclo- DNA crosslinks CYP3A4, and through aldehyde phosph- and also hepatic low-moderate dehydrogenase amide CYP2C9 metabolism. emetogenicity may Ifosfamide is a 3. increase explain its major substrate coadministration DNA repair by altered of CYP3A4. of mesna MGMT efficacy half-life of parent and drug ~8hours toxicity profiles Mesna Prevention of 50% oral Mild at clinical Half-life of hemorrhagic cystitis bioavailability; doses mesna is Uromitexan â by reacting with drug is rapidly shorter acrolein (a cleared from not emetogenic than cyclo- metabolite of plasma and phosphami cyclophosphamide) converted back to de; needs to form stable, non- parent drug in continuous urotoxic compounds renal tubules infusion or Page 6 of 13 PHRM311 Oncology - Drug Lists Dr. Judy Wong before secretion multiple into urine for its doses for protective protective function effects Platinum Compounds Cisplatin Inter and intra- Parent mainly IV and Myelosuppression 1. reduced Synergy strand DNA drug is IP in special nephrotoxicity, intracellular with Platinolâ crosslinking; activated applications; peripheral sensory drug etoposide Platinol-AQâ N7 of guanine is a by cisplatin is 90% neuropathy, concentration particularly active hydrolysis. protein bound; ototoxicity with site Quick unbound drug is cumulative drug kinetics. rapidly cleared dose and is 2. increased from plasma and irreversible, nerve capacity of excreted by the dysfunction glutathione kidney Highly emetic and/or other Carboplatin Activated IV infusion. Carboplatin is less sulfhydryls to Effective by Majority of nephrotoxic and inactivate alternative Paraplatin â hydrolysis parent drug in ototoxic than drugs to cisplatin ParaplatinAQ â to form unbound form; cisplatin; in patients reactive reactive platinum myelosuppression, with platinum metabolite is nausea and 3.over- impaired compound. 90% protein vomiting expression of renal Conversion bound; majority High-moderate nucleotide function. is much of drug is emetic excision repair slower than eliminated by (NER) genes cisplatin renal excretion Oxaliplatin Parent IV only; short Peripheral Synergy drug is half-life in sensory with 5-FU Eloxatin â activated plasma and neuropathy, and by rapidly anemia, diarrhea, irinotecan. hydrolysis redistributed; myelosuppression, to form renal excretion and renal toxicity reactive Pt compound. Page 7 of 13 PHRM311 Oncology - Drug Lists Dr. Judy Wong High-moderate emetic Anthracyclines Antibiotics Doxorubicin 1. Formation of IV bolus and IP Myelosuppression, 1. over- Con- tripartite complex in special congestive heart expression of comitant Adriamycin â with Topo II and applications; failure P-glycoprotein administr DNA excreted by a drug efflux ation of combination of dose-related high pump. dexrazo- 2. Intercalates DNA hepatic moderate xane may and inhibits metabolism emetogenicity 2. decreased reduce transcription and (aldo-keto Topo II cardiac replication reductase) and activity damage biliary excretion 3. Formation of free mechanism. 3. increased radicals and glutathione induced oxidative peroxidase Epirubicin stress IV bolus Reduced cardiac metabolism administered. toxicity compared Pharmorubicin â Extensive hepatic to doxorubicin; Ellence â metabolism Myelosuppression dose-related high moderate emetogenicity Page 8 of 13  PHRM311 Oncology - Drug Lists Dr. Judy Wong Poly-ADP-Ribose Polymerase Inhibitors Drug Mechanism of Action ADME Toxicities Resistance Notes Olaparib PARP1 and 2 orally administered. Does not Myleosuppression 1. Increase Inter- Inhibitors: cross BBB drug efflux by patient Lynoparza â 1) inhibits single Rare pneumonitis PgP variability stranded DNA breaks Metabolized by CYP3A4 can be fatal and drug repair by BER 2. restoration inter- Eliminate by renal and GI of HR repair actions 2) cause routes due to accumulations of 3. increase CYP3A4 ssDSB that change to DNA involve- DSB during DNA replication ment. replication à fork repair specific toxicities to Niraparib HR-negative cancers orally administered. Cross Myleosuppression Pre- BBB. existing Zejula â 3) impaired CVS toxicities hyper- replication fork Metabolise by carboxyl- Hypertension and tension repair esterase hypertensive crisis needed to be well- Eliminate by renal Rare intestinal controlled hepatobiliary and GI routes perforations can be prior to Rx fatal Molecular Targeted Anti-Cancer Chemotherapeutic Agents Small Molecule Tyrosine Kinase Inhibitor Agents Mechanism of Action ADME Toxicities Resistances NOTES Palbociclib Inhibits CDK4/6 and arrest cell Orally Myelosuppression. For all 3 Interpatient cycle at G1/S and apoptosis. administered. 46% Low but recognized agents variability and Ibranceâ Competitive binding at the ATP bioavailability risk of pulmonary drug binding site leads to inhibition of metabolized by embolism. 1. Loss of Rb1 interaction downstream phosphorylation of CYP3A and Teratogenic. must be protein targets. sulfotransferase 2A. considered due Page 9 of 13  PHRM311 Oncology - Drug Lists Dr. Judy Wong Excreted mainly as 2. E2F to CYP3A4 metabolites by fecal amplification involvement. route. Ribociclib Orally Myelosuppression. 3. aberrant administered. QT prolongation, cyclin E Kisqaliâ Extensively rare hepatotoxicity signaling metabolized by (2%) but therapeutic CYP3A4. excreted monitoring required, 4. Increase in mainly as pulmonary drug efflux metabolites by fecal embolism. via ABC- route. transporters counter-indicated in untreated congenital long QT syndrome cases Abemaciclib Orally Myelosuppression. administered. 45% Diarrhea (90%, Verzenioâ bioavailability severe in less than metabolized by 1%) CYP3A4. Excreted psychiatric (anxiety mainly as and insomnia), rare metabolites by fecal interstitial lung route. diseases but could be fatal Imatinib Inhibits BCR-Abl tyrosine kinase. Orally Myelosuppression 1. mutation in Interpatient Competitive binding at the ATP administered. 98% Edema tyrosine variability and Gleevecâ binding site leads to inhibition of bioavailability Hepatic kinase drug downstream phosphorylation of 75% oxidized by disturbances, (particularly interaction protein targets. Also inhibits CYP3A4/5; severe skin reactions T315I) must be tyrosine kinase for platelet-derived excreted by both considered due growth factor and c-Kit. renal and fecal HBV reactivation 2. amplifi- to CYP3A4 New congeners to overcome TKI routes cation of involvement. resistance include nilotinib, BCR-Ab dasatinib, bosatinib and ponatinib Page 10 of 13  PHRM311 Oncology - Drug Lists Dr. Judy Wong (only congener active against 3. increase T315I-TK mutation) drug efflux Gefitinib Epidermal growth factor (EGFR) Orally Diarrhea, 1. KRAS Low response tyrosine kinase inhibitor, administered. 60% nausea and mutations rate in clinical Iressaâ competitively inhibits ATP bioavailability vomiting; use to date; binding 90% plasma protein interstitial lung 2. HER-1-TK perhaps EGFR bound; extensive disease is rare but mutations is not hepatic metabolism fatal; (particularly indispensable via CYP3A4; QT prolongation; T790M) for tumor excreted via both infusion-related survival renal and fecal toxicity; skin rash 3. drug efflux routes. increase Monoclonal Antibodies against EGFR Cetuximab Recombinant, chimeric monoclonal IV infusion. Half Acne-like rash that Increase KRAS and antibody (IgG1) directed against the life ranges from 2.6 could lead to Rx signal BRAF Erbituxâ epidermal growth factor (EGFR, to 9.5 days termination. May transduction (oncogenes) HER1). cause cardio- through the mutational Activates the complement-mediated low emetogenicity pulmonary arrest increase of status impacts cell toxicity, and prevents the and interstitial lung EGFR1 copy therapeutic activation of EGFR, lead to its anti- disease in small number, or usefulness of cancer effects. percent of patients switch to the these Pani- Fully humanized monoclonal IV infusion. Half Acne-like rash that alternate monoclonal tumumab antibody (IgG2) directed against the life ranges from 3.6 could lead to HER2/neu antibodies epidermal growth factor (EGFR, to 10.9 days termination of protein signal Vectibixâ HER1). therapy. Acute transduction Receptor target-mediated saturable low emetogenicity renal failure may pathway binding to EGFR and subsequent present in patients internalization and degradation. with dehydration from severe diarrhea Page 11 of 13  PHRM311 Oncology - Drug Lists Dr. Judy Wong Other Signal Transduction Disruptive Monoclonal Antibodies Trastuzumab Recombinant DNA-derived IV infusion; Cardiomyopathy Increases humanized monoclonal antibody degradation through (especially in EGFR Herceptinâ (IgG1); it binds to the epidermal irreversible receptor combination with dependent growth factor receptor 2 (HER2); binding. Half-life is anthracyclines), signal HER2 is over-expressed in 25-30% 5.8-21 days infusion-related transduction of cases of Breast Cancers toxicity(fever, activity low emetogenicity chills, nausea, dyspnea, rashes) Bevacizumab Monoclonal antibody (IgG1) that IV infusion; GI perforations, Increased Adverse drug binds to the vascular endothelial administered every hemorrhage, activities of reaction are Avastinâ growth factor (VEGF) and prevents two weeks and has impaired wound alternate unique for mAb the activation of VEGF receptor- an estimated half- healing, severe angiogenesis and potentially mediated endothelial cell life of 20 days dose-dependent pathways, serious. proliferation; inhibition of hypertension, bypassing angiogenesis will delay tumor rare emetogenicity proteinuria VEGF growth and prevent metastatic disease progression Monoclonal antibodies in Immune Checkpoint therapies Ipilimumab Fully humanized monoclonal IV infusion over a Immune–mediated mutations and Signs and antibody (IgG2) directed against period from 30-90 adverse reactions, disruptions of symptoms Yervoyâ CTLA4 min sometimes fatal, can tumor IFN-g suggestive of involve any organ pathway immune-related CTLA4 are found on T-cells system. GI tract, reactions may Nivolumab Fully humanized monoclonal IV infusion over 60 liver, skin, Reduction in be nonspecific. antibody (IgG2) directed against min endocrine, and tumor Opdivoâ PD-1 nervous systems are neoantigen Immune- most commonly presentation mediated PD-1 are found on T-cells and other involved. Diarrhea, toxicities have immune cells bloody stool, liver been reported, enzyme elevations, even after Page 12 of 13  PHRM311 Oncology - Drug Lists Dr. Judy Wong rash, and endocrino- Changes in discontinuation pathologies must be tumor of the drug. considered immune- microenvirone mediated. ment Pembroli- Fully humanized monoclonal IV infusion over 30 severe infusion- zumab antibody (IgG4) directed against min related reactions in Upregulation PD-1 addition to immune- of other Keytrudaâ mediated adverse checkpoint PD-1 are found on T-cells and other reactions inhibitors immune cells Atezoli- All three are fully humanized IV infusion over a irAEs and infusion zumab monoclonal antibody (IgG1) period from 30-60 related reactions directed against PD-L1 min Tecentriqâ PD-L1 are found on tumor cells and Avelumab normally in a range of immune and IV infusion over 60 parenchymal tissues min Bavencioâ Durvalumab IV infusion over 60 min Imfinziâ Page 13 of 13