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
  • Cancer-related Cachexia
  • 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
  • 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)
  • Anti-CD52
  • Use: CLL, MS
  • 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)
  • Use: RCC
  • 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
    • Increases digoxin levels
  • 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
    • Blocks BCR-ABL fusion
  • Can be held without significant change in labs, may hold for entire pregnancy without problems
  • SE: Nausea
  • Ifosfamide
  • SE: hemorrhagic cystitis
  • 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)
    • SE: PRES syndroms
    • Thalidomide (Thalomid)
    • Topoisomerase Inhibitors
    • Cell Cycles affected: S, G2
    • MOA: Eukaryotic Topoisomerase I Inhibitors
    • Topotecan
    • Used in ovarian and small cell lung cancer
    • Irinotecan
    • Used in Colon cancer
    • 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)