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Cancer Drug Pharmacology Table

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CANCER DRUG PHARMACOLOGY TABLE Cytotoxic Chemotherapy Drugs are classified according to the BC Cancer Drug Manual Monographs, unless otherwise specified (see asterisks). Subclassifications are in brackets where applicable. Alkylating Agents have reactive groups (usually alkyl) that attach to Antimetabolites are structural analogues of naturally occurring molecules DNA or RNA, leading to interruption in synthesis of DNA, RNA, or required for DNA and RNA synthesis. When substituted for the natural body proteins. substances, they disrupt DNA and RNA synthesis. bendamustine (nitrogen mustard) azacitidine (pyrimidine analogue) busulfan (alkyl sulfonate) capecitabine (pyrimidine analogue) carboplatin (platinum) cladribine (adenosine analogue) carmustine (nitrosurea) cytarabine (pyrimidine analogue) chlorambucil (nitrogen mustard) fludarabine (purine analogue) cisplatin (platinum) fluorouracil (pyrimidine analogue) cyclophosphamide (nitrogen mustard) gemcitabine (pyrimidine analogue) dacarbazine (triazine) mercaptopurine (purine analogue) estramustine (nitrogen mustard with 17-beta-estradiol) methotrexate (folate analogue) hydroxyurea pralatrexate (folate analogue) ifosfamide (nitrogen mustard) pemetrexed (folate analogue) lomustine (nitrosurea) pentostatin (purine analogue) mechlorethamine (nitrogen mustard) raltitrexed (folate analogue) melphalan (nitrogen mustard) thioguanine (purine analogue) oxaliplatin (platinum) trifluridine-tipiracil (pyrimidine analogue/thymidine phosphorylase procarbazine (triazine) inhibitor) streptozocin (nitrosurea) temozolomide (triazine) thiotepa (aziridine) treosulfan BC Cancer Pharmacy Education Program Cancer Drug Pharmacology Table 1/9 Author: Rhonda Kalyn, BC Cancer Reviewer: Mario de Lemos, BC Cancer Published: 2018-02-06 Updates: BC Cancer CON Pharmacy Educators Updated: 2021-06-02 Antimicrotubule Agents (Mitotic Inhibitors) inhibit cell mitosis by Topoisomerase Inhibitors (I and II) cause DNA strand breaks by disrupting the interfering with microtubule formation or function. function of topoisomerase enzymes, which are responsible for regulating the 3-D structure of DNA. cabazitaxel (taxane) docetaxel (taxane) eribulin Topoisomerase I ixabepilone paclitaxel (regular and nanoparticle, albumin-bound) (taxane) irinotecan vinblastine (vinca alkaloid) topotecan vincristine (vinca alkaloid) vinorelbine (vinca alkaloid) Topoisomerase II amsacrine Miscellaneous Antineoplastics - Refer to BC Cancer monographs for anthracyclines pharmacology. - daunorubicin dactinomycin - doxorubicin (regular and pegylated liposomal) arsenic trioxide mitotane iniparib - epirubicin asparaginase porfimer lurbinectedin - idarubicin bleomycin romidepsin mitomycin etoposide belinostat vorinostat mitoxantrone teniposide Hormonal Therapies Aromatase Inhibitors (AIs) prevent the final step in the conversion of Antiestrogens oppose the effects of estrogen. androgens to estrogens in peripheral tissues. tamoxifen – partial estrogen antagonist (antagonist on breast anastrozole tissue, agonist on endometrium, bone and lipids) exemestane fulvestrant – full estrogen antagonist (no agonist activity) letrozole Luteinizing Hormone Releasing Hormone (LHRH) Agonists (also known as Antiandrogens opposes the effects of androgens. gonadotropin releasing hormone analogues) initially stimulate the release of apalutamide luteinizing hormone, which leads to an increase in sex hormones BC Cancer Pharmacy Education Program Cancer Drug Pharmacology Table 2/9 Author: Rhonda Kalyn, BC Cancer Reviewer: Mario de Lemos, BC Cancer Published: 2018-02-06 Updates: BC Cancer CON Pharmacy Educators Updated: 2021-06-02 bicalutamide (testosterone, estradiol). Chronic use leads to down-regulation of the LHRH darolutamide receptors, leading to decreased testosterone in men and estrogen in women. enzalutamide – more affinity for androgen receptors and Plus buserelin inhibits more steps in the androgen inhibition than other agents goserelin in this class leuprolide flutamide nilutamide Luteinizing Hormone Releasing Hormone (LHRH) Antagonist (also known as gonadotropin releasing hormone antagonist) reduce the release of luteinizing Androgen Biosynthesis Inhibitors hormone, follicle-stimulating hormone, and consequently testosterone by the abiraterone - selectively inhibits the enzyme (CYP17) that testes. converts pregnenolone and progesterone into testosterone degarelix precursors. Progestins suppress the release of luteinizing hormone from the pituitary Androgens gland and subsequently decrease estrogen levels. Additional mechanisms testosterone - The exact mode of action for androgen therapy in include binding to progesterone, glucocorticoid, and androgen receptors, breast cancer is unclear. resulting in decreased number of estrogen receptors and decreased estrogen and progesterone levels peripherally in target tissues. Corticosteroids are thought to act via apoptosis induction. medroxyprogesterone dexamethasone megestrol prednisone Prolactin Lowering Agents are dopamine antagonists that decrease hormone Somatostatin Analogues inhibit exocrine and endocrine secretion of production and the size of prolactin-dependent pituitary adenomas by hormones, which is useful for hormone-secreting tumours (e.g., inhibiting the release and synthesis of prolactin from the anterior pituitary. neuroendocrine). Additional mechanisms include modulation of bromocriptine biliary/GI motility and apoptosis inductions. cabergoline lanreotide quinagolide octreotide Thyrotropin Stimulating Hormone Agonist is a recombinant thyrotropin used for serum thyroglobulin testing in thyroid cancer. BC Cancer Pharmacy Education Program Cancer Drug Pharmacology Table 3/9 Author: Rhonda Kalyn, BC Cancer Reviewer: Mario de Lemos, BC Cancer Published: 2018-02-06 Updates: BC Cancer CON Pharmacy Educators Updated: 2021-06-02 thyrotropin alpha Immunotherapies Cytokines are proteins that are involved in the cell signaling that Immunomodulatory Drugs (IMIDs) have multiple mechanisms of action, leads to immune responses at sites of inflammation, infection, and including inhibition of proliferation of certain hematopoietic tumour cells, trauma. They induce various cellular responses, such as suppression enhancing numbers and activity of T, NK, and NK T cells, and inhibition of of cell proliferation and augmentation of the cytotoxicity of angiogenesis. lymphocytes. lenalidomide aldesleukin pomalidomide interferon thalidomide peginterferon Differentiating Agents are vitamin A derivatives. Their proposed mechanism Vaccine Therapy of action is to overcome impaired cellular differentiation. bacillus calmette-guerin (BCG) acitretin - a live, attenuated bacteria (Mycobacterium bovis) that exerts bexarotene a variety of antitumour actions, including induction of a local tretinoin granulomatous reaction, activation of histiocytes, and other direct and indirect stimulation of immune responses. The result is a local inflammatory response that destroys tumour Other Immunotherapies cells. imiquimod – TLR7 agonist Monoclonal antibodies could also be considered immunotherapies, particularly those that inhibit CTLA-4, PD-1 or PD-L1 (Checkpoint Inhibitors), or IL-6. They are covered on the pages that follow. Targeted Therapies Targeted therapies target receptors, ligands, or intracellular molecules involved in the signal transduction of cancer cells. The following table is a listing of targeted therapies with the target(s) listed in brackets. See the following page for more information on targets. Note that the relative affinity to particular targets is not always clear for each agent, and may differ when used in different indications. Some of the available literature refer to drugs by their target, such as EGFR-inhibitors or multikinase inhibitors for oral drugs with multiple targets (e.g., pazopanib,sorafenib, sunitinib). BC Cancer Pharmacy Education Program Cancer Drug Pharmacology Table 4/9 Author: Rhonda Kalyn, BC Cancer Reviewer: Mario de Lemos, BC Cancer Published: 2018-02-06 Updates: BC Cancer CON Pharmacy Educators Updated: 2021-06-02 abemaciclib (CDK 4/6) dasatinib (BCR-ABL, LYN, HCK, c-kit, EPH, palbociclib (CDK 4/6) acalabrutinib (BTK) PDGFβ) pazopanib (VEGFR 1, 2, 3, c-KIT, PDGFR-α,-β, afatinib (EGFR, HER2, HER4) denosumab (RANKL) c-KIT,FGFR-1 and -3, IL-2, and c-Fms) AGS-16C3F (MMAF) (antibody conjugated dinutuximab (GD2) pembrolizumab (PD-1) with cytotoxic) durvalumab (PD-L1) pertuzumab (HER2) alectinib (ALK) erlotinib (EGFR) polatuzumab vedotin (CD79b) (antibody alemtuzumab (CD52) entrectinib (ROS1 and NTRK) conjugated with cytotoxic) atezolizumab (PD-L1) everolimus (MTOR) ramucirumab (VEGFR2 and VEGF A, C, and D) avelumab (PD-L1) gefitinib (EGFR) regorafenib (VEGFR-1, -2, & -3, TIE2, KIT, RET axitinib (VEGFR 1, 2, & 3) gemtuzumab ozogamicin (CD33) (antibody RAF-1, BRAF, BRAV600E, PDGFR, FGFR) bevacizumab (VEGF) conjugated with cytotoxic) ribociclib (CDK 4/6) belantamab mafodotin (IgG1) (antibody gilteritinib (FLT-3) rituximab (CD20) conjugated with cytotoxic) ibrutinib (BTK) ruxolitinib (JAK 1 & 2) blinatumomab (CD3 & CD19) idelalisib (PI3Kδ) sacituzumab govitecan (IgG1.k antibody bortezomib (26S proteosome) imatinib (BCR-ABL, PDGF, c-KIT) conjugated with cytotoxic) brentuximab vedotin (CD30) (antibody inotuzumab ozogamicin (CD22) (antibody siltuximab (IL-6) conjugated with cytotoxic) conjugated with cytotoxic) Sonidegib (Hh) cabozantinib (MET, VEGF, FLT3) ipilumumab (CTLA-4) sorafinib (c-Raf,b-Raf, V600E,b-Raf,KIT,FLT-3,
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  • In Vivo Characterization of Combination Antitumor Chemotherapy with Calcium Channel Blockers and Ci5-Diamminedichloroplatinum(II)1

    In Vivo Characterization of Combination Antitumor Chemotherapy with Calcium Channel Blockers and Ci5-Diamminedichloroplatinum(II)1

    (CANCER RESEARCH 49, 2844-2850. June 1, 1989] In Vivo Characterization of Combination Antitumor Chemotherapy with Calcium Channel Blockers and ci5-Diamminedichloroplatinum(II)1 James M. Onoda,2 Kevin K. Nelson, John D. Taylor, and Kenneth V. Honn Departments of Radiation Oncology [J. M. O., K. K. N., J. D. T., K. V. H.], Biological Sciences [J. D. T.], and Chemistry ¡K.V. H.], Wayne State University, Detroit, Michigan 48202; and the Cershenson Radiation Oncology Center [J. M. O., K. K. N., J. D. T., K. V. H.], Harper/Grace Hospitals, Detroit, Michigan 4820I ABSTRACT dulin antagonists to enhance the antitumor actions of the more We have examined nifedipine, a dihydropyridine class calcium channel commonly prescribed organic or natural product chemothera blocker, for ability to overcome m-diamminedichloroplatinum(II) (cis- peutic agents (3, 4). The ability of verapamil to reverse multi- platin) resistance in a murine tumor line variant, B16a-Pt, which we drug resistance or pleiotropic drug resistance correlates with developed for resistance to cisplatin. Nifedipine significantly enhanced the expression of a M, 170,000 glycoprotein in drug-resistant the antitumor actions of cisplatin against primary subcutaneous B16a-Pt tumor cell plasma membranes (5, 6). This glycoprotein is now tumors and their spontaneous pulmonary métastases.We have charac commonly referred to as the P-glycoprotein (7, 8) and is re terized, in vivo, the pharmacokinetics and dose-response interactions sponsible for the active efflux of many organic/natural product between nifedipine and cisplatin. We now report our studies designed to cytotoxic chemotherapeutic agents (9-11). The current hypoth compare, in vivo, the efficacy of nifedipine and other calcium active esis suggests that verapamil interacts with the P-glycoprotein compounds including: (a) structurally similar calcium channel blockers to block drug efflux (12, 13); and that its actions are independ (nimodipine, nicardipine) from the dihydropyridine class, (b) structurally ent of the classical slow-inward Ca2+ channel (14, 15).