Oncologic Meds General New Afib in cancer patients is associated with increased risk of HF and VTW Common Groups ABVD Adriamycin, Bleomycin, Vinblastine, Dacarbazine Hodgkin Lymphoma BEACOPP Bleomycin, Etoposide, Adriamycin/doxorubicin, Cyclophosphamide, Oncovorin/vincristine, Procarbazine, Prednisone Hodgkin Lymphoma FOLFOX Leucovorin, Fluorouracil, Oxaliplatin R-CHOP Rituximab, Cyclophosphamide, Hydroxy-doxorubicin, Oncovorin/Vincristine, Prednisone 5-Fluorouracil (5-FU) MOA: Direct Inhibitor of pyrimidine synthesis (blocks thymidylate synthase), thereby blocking protein and DNA synthesis Leucovorin increases 5-FU effectiveness Anti-metabolite Inflammation resolves about 2 weeks after treatment discontinuation SE: Myelosuppression and Photosensitivity, Palmar-plant erythrodysesthesia (hand-foot syndrome), cerebellar toxicity 6-Mercaptopurine (6-MP) Anti-metabolite, metabolized by xanthine oxidase (inhibited by allopurinol) Side effects are worse when on allopurinol (stop or reduce) Thiopurine SE: Myelosuppressive, Hepatotoxic, Interacts with allopurinol Azathioprine Converted to 6-MU and also metabolized by xanthine oxidase, also interacts with allopurinol Alemtuzumab (Lemtrada) All-Trans Retinoic Acid (ATRA) MOA: Inhibits transcriptional repression by PML-RARa Tretinoin Formulation of Vitamin A, targeted therapy for Acute Promyelocytic Leukemia (M3 variant) Causes immature myeloblasts to differentiate into mature myelocytes Combined with an Anthracycline (Daunorubicin, Idarubicin) for best results SE: Rashes, Teratogenic, DIC Aromatase Inhibitors Anastrozole, letrozole, and vorozole Block formation of new estrogen (good for metastatic disease) Give Calcium and Vitamin D supplements, Get DEXA Bisphosphonates or denosumab if osteoporotic Increased risk of osteoporosis and fracture SE: Arthralgia, joint stiffness and bone pain in 33%, Vaginal dryness, sexual dysfunction, CV events, hyperlipidemia, and higher risks of osteoporosis and fractures Axitinib (Inlyta) Bevacizumab (Avastin) Anti-VEGF Use: Colorectal cancer, renal cell carcinoma, non-small cell lung cancer SE: PRES syndrome Bleomycin Antitumor antibiotic used in testicular cancer and Hodgkin's Lymphoma No myelosuppression (vs. Busulfan) Induces free radical formation and cause breaks in DNA SE: Severe Pulmonary Fibrosis, Fever, and hypersensitivity Bortezomib (Velcade) MOA: Proteasome inhibitor SE: Peripheral Neuropathy, Herpes Reactivation Prophylactic acyclovir or valacyclovir Busulfan Alkylates DNA Pulmonary Fibrosis and myelosuppression Capecitabine (Xeloda) Adjuvant for colon cancer SE: Palmar-plant erythrodysesthesia (hand-foot syndrome) Caplacizumab (Cablivi) Monoclonal antibody Use: Severe TTP Cetuximab (Erbitux) Anti-EGFR Stage IV colorectal cancer, head and neck cancers SE: Pustular acneiform eruptions (severe), pulmonary toxicity Chemotherapy-Induced Cardiotoxicity Type I Associated with Anthracyclines Daunorubicin Doxorubicin (Adriamycin, Doxil) Idarubicin Generate free radicals to intercalate DNA Causes severe tissue necrosis Myocyte Necrosis and destruction w/fibrosis Progression to overt clinical heart failure Less likely to be reversible SE: Dilated Cardiomyopathy with chronic use Antitumor Antibiotic, myelosuppression, alopecia, severe gastric upset secondary to colonic mucositis Total cumulative dose is most strongly related to risk Antidote is Dexrazoxane Iron-chelating agent used for cardiac protection Type II Associated with Trastuzumab Myocardial stunning/hibernation w/o myocyte destruction Asymptomatic LV systolic dysfunction More likely to be reversible Cyclophosphamide (Cytoxan) Covalently links DNA at guanine N-7 SE: Hemorrhagic Cystitis, SIADH (hyponatremia), bladder carcinoma, myelosuppression, sterility (acrolein, metabolite causes all the damage) Cystitis can be treated with 2-Mercaptoethanesulfonate (Mensa) which binds the metabolite acrolein (bladder irritant), fluids Alkylating agents put patient at risk for developing secondary cancer (Acute Leukemia) Dactinomycin Intercalates DNA Used in Wilms' Tumor, Ewing Sarcoma, Rhabdomyosarcoma Dasatinib (Sprycel) Tyrosine Kinase Inhibitor Used in CML SE: pulmonary hypertension Daunorubicin (Cerubidine) Anthracyclines Generate free radicals to intercalate DNA Causes severe tissue necrosis SE: Dilated Cardiomyopathy with chronic use, Mucositis, stomatitis Antitumor Antibiotic, myelosuppression, alopecia, severe gastric upset secondary to colonic mucositis Total cumulative dose is most strongly related to risk Antidote is Dexrazoxane Iron-chelating agent used for cardiac protection Doxorubicin (Hydroxydaunomycin) SE: Mucositis, stomatitis Eculizumab MOA: Monoclonal antibody against C5, blocks cleavage and blocks formation of the C5-9 complex Used in Paroxysmal nocturnal hemoglobinuria Elotuzumab MOA: Activating NK cells to kill MM cells, Targets SLAMF7 Erlotinib SE: Pustular acneiform eruptions (weak), pulmonary toxicity Folinic Acid (Leucovorin) Gefitinib SE: Pustular acneiform eruptions (weak) Hydroxyurea MOA: Inhibits ribonucleotide reductase, decreasing DNA synthesis Use: Essential Thrombocytopenia, PCV Ibrutinib (Imbruvica) Tyrosine Kinase Inhibitor, binds BTK Metabolized by CYP3A4 Use: CLL, B-cell Lymphoma SE: Increased rates of Atrial Fibrillation (up to 16%) – Don't use CCBs Imatinib (Gleevec) MOA: Blocks ATP binding to tyrosine kinase active site Use: CML, GIST Can be held without significant change in labs, may hold for entire pregnancy without problems SE: Nausea Ifosfamide Lenalidomide (Revlimid) Methotrexate MOA: Folate Antagonist (Dihydrofolate Reductase Inhibitor) Converts oxidized folate back into its reduced form to be used in pyrimidine synthesis Can be bypassed/fixed by Leucovorin (N5-formyltetrahydrofolate) used in Rheumatoid Arthritis also Stops DNA and protein synthesis hindering S-phase SE: Myelosuppression and Abortifacient, Hepatotoxicity, stomatitis, cytopenia Microtubule Inhibitors Taxols/Taxanes MOA: Inhibit microtubule degradation Bind polymerized microtubules and stabilize the mitotic spindle so it can not break down Inhibiting dynein Cell phase: M phase SE: Some myelosuppression Paclitaxel (Taxol) Nab-paclitaxel (Abraxane) Docetaxel (Taxotere) Vinca Alkaloids MOA: Inhibits microtubule production and assembly Bind B-tubulin and block polymerization, therefore the mitotic spindle cannot form Inhibit kinesin Cell phase: M phase Use: Hematologic and solid malignancies SE: Alopecia, Paralytic ileus/constipation Vincristine: Use: Non-Hodgkin SE: Peripheral Neuropathies (Neurotoxic), Alopecia Stocking and glove distribution Areflexia, peripheral neuritis, motor symptoms less commonly Autonomic dysfunction Paralytic ileus/constipation Some myelosuppression usually mild Vinblastine Use: Hodgkin SE: Profound Bone Marrow Suppression, Alopecia Mitomycin Antitumor Antibiotic SE: Hemolytic Uremic Syndrome Nilotinib SE: Coronary insufficiency Nitrosoureas Can cross BBB to treat brain cancer SE: pulmonary fibrosis Carmustine Lomustine Semustine Streptozocin Panitumumab (Vectibix) SE: Pustular acneiform eruptions (severe) Platinum Drugs General Prevent nephrotoxicity with Amifostine Magnesium wasting (hypomagnesemia) Carboplatin Platinum Alkylating Agent Hydrate well to protect the kidneys, highly emetogenic (give something for vomiting) SE: Myelosuppression is main/dose limiting SE Less other SE than Cisplatin Ototoxicity and Nephrotoxicity Less nephrotoxic than Cisplatin Cisplatin Platinum Alkylating Agent Prevents replication of tumor cells by causing intra-stand links within DNA SE: Myelosuppression, Peripheral Neuropathies (stocking glove), Nephrotoxic (ATN), Ototoxic, electrolyte abnormalities, Tinnitus, N/V Less nephrotoxic with aggressive hydration Oxaliplatin SE: Peripheral Neuropathies (stocking glove), transient cold hypersensitivity No cold items for several days after infusions Ponatinib SE: Coronary insufficiency Purine Analogs MOA: Cytotoxic purine analog Inhibits DNA polymerase Alpha and Beta SE: Immunosuppression Cladribine/Pentostatin Used in symptomatic hairy cell leukemias Pyrimidine Analogs MOA: Cytotoxic pyrimidine analog Inhibits DNA polymerase Alpha and Beta SE: Immunosuppression/Myelosuppression Gemcitabine (Gemzar) Used in hematologic and solid tumors, small-cell SE: Severe Pulmonary Fibrosis, Hemolytic Uremic Syndrome Cytarabine (Ara-C) Aka Arabinofuranosyl Cytidine Used in Non-M3 AML, non-Hodgkin Lymphoma hematologic cancers only Cell Cycle: S phase SE: Megaloblastic Macrocytic anemia, cerebellar toxicity Radiation MOA: Damages DNA, preventing tumor cell division or directly killing the cells Can decrease the tumor size or kill any existing tumor cells SE: Slower wound healing, fibrosis, ulcerations, strictures, irritation, neurologic deficits, BM suppression, 2ndary cancers (sarcomas, thyroid cancer, CML) Goals: First line in some tumors Eradicate smaller tumors Sensitize cancer cells to radiation therapy Selective Estrogen Receptor Antagonist (SERM) Tamoxifen Antagonist in the breasts, Agonist in the Endometrium and bone SE: Deep Venous Thrombosis (DVT), hot flashes, endometrial cancer risk, teratogenic Raloxifene Antagonist in the breasts and endometrium, agonist in bone (osteoporosis treatment) No increased risk for cancer SE: Deep Venous Thrombosis (DVT), hot flashes Sunitinib (Sutent) Thalidomide (Thalomid) Topoisomerase Inhibitors Cell Cycles affected: S, G2 MOA: Eukaryotic Topoisomerase I Inhibitors Topotecan Used in ovarian and small cell lung cancer Irinotecan SE: Severe/Life-threatening Diarrhea MOA: Eukaryotic Topoisomerase II Inhibitors Etoposide Teniposide Inhibits relegation of double strand breaks caused by topoisomerase II Used in a regimen with bleomycin and cisplatin for testicular masses, small cell lung cancer, Hodgkin and non-Hodgkin Lymphoma SE: Alopecia, myelosuppression, Immunosuppression Trastuzumab MOA: Anti-HER2/neu antibody Binds HER2 on tumor surface and induces receptor internalization Use: HER2 (+) Breast cancer, Gastric cancer SE: Type II Cardiotoxicity, pulmonary toxicity, oligohydramnios Avoid pregnancy for 7 months last dose Tretinoin Formulation of Vitamin A, targeted therapy for Acute Promyelocytic Leukemia (M3 variant) SE: Rashes, Teratogenic Vincristine (Oncovorin) Hypercatabolic state characterized by appetite and weight loss with a disproportionate loss of skeletal muscle Treatment Progesterone analogs (Megestrol acetate, Medroxyprogesterone) and corticosteroids (Dexamethasone) PAs preferred in pts with longer life expectancies