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Chapter 45: Cancer Chemotherapy and Cytotoxic Agents

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    AMA Citation
    Cancer Chemotherapy and Cytotoxic Agents. In: Rollins DE, Blumenthal DK. Rollins D.E., Blumenthal D.K. Eds. Douglas E. Rollins, and Donald K. Blumenthal.eds. Workbook and Casebook for Goodman and Gilman's The Pharmacological Basis of Therapeutics New York, NY: McGraw-Hill; . http://accesspharmacy.mhmedical.com/content.aspx?bookid=1697&sectionid=111006088. Accessed April 10, 2020.
    MLA Citation
    . "Cancer Chemotherapy and Cytotoxic Agents." Workbook and Casebook for Goodman and Gilman's The Pharmacological Basis of Therapeutics Rollins DE, Blumenthal DK. Rollins D.E., Blumenthal D.K. Eds. Douglas E. Rollins, and Donald K. Blumenthal. New York, NY: McGraw-Hill, , http://accesspharmacy.mhmedical.com/content.aspx?bookid=1697&sectionid=111006088.

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INTRODUCTION

This chapter will be most useful after having a basic understanding of the material in Chapter 60 General Principles of Cancer Chemotherapy and Chapter 61 Cytotoxic Agents in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th Edition. In addition to the material presented here, Chapters 60 and 61 of the 12th Edition contain:

  • A description of the cell cycle, and cell cycle checkpoints and regulation

  • The clinical pharmacology and toxicities of specific agents

  • The molecular structures of cytotoxic agents used to treat cancer and other diseases such as immune disorders

LEARNING OBJECTIVES

  • Understand the mechanisms of action of cytotoxic antineoplastic agents on tumor cells (see Figure 45-1).

  • Understand the mechanisms of toxicity of cytotoxic antineoplastic agents on normal cells and strategies for reducing toxic effects.

  • Understand the mechanisms of drug resistance to individual agents and strategies to avoid resistance.

  • Know how pharmacogenetics can impact tumor sensitivity and toxicities of specific agents.

  • Know the signs of acute toxicity and when chemotherapy should be altered or discontinued.

  • Know the risk of long-term toxicities that can occur with individual chemotherapeutic agents.

  • Know the therapeutic strategies that can reduce acute and chronic toxicities.

  • Know which classes of agents are typically used in treating specific cancers.

  • Know which drugs are used in combination to improve tumor cell killing and reduce the risk of resistance development.

DRUGS INCLUDED IN THIS CHAPTER

  • 2-Mercaptoethanesulfonate (mesna; MESNEX)—reacts with acrolein in urine and protects against severe hemorrhagic cystitis in high-dose cyclophosphamide regimens

  • 5-Fluorouracil (5-FU)

  • 6-Mercaptopurine (6-MP; PURINETHOL, others)

  • 6-Thioguanine (6-TG)

  • Altretamine (hexamethylmelamine; HEXALEN)

  • Amifostine (WR-2721; ETHYOL, others)—thiophosphate cytoprotective agent (see cisplatin clinical toxicities)

  • Arsenic trioxide (ATO; TRISENOX)

  • Azacytidine (5-azacytidine)

  • Bendamustine (TREANDA, others)

  • Bleomycin (BLENOXANE, others)

  • Busulfan (MYLERAN, BUSULFEX)

  • Carmustine (BCNU; BICNU, GLIADEL)

  • Capecitabine (XELODA)

  • Carboplatin (CBDCA, JM-8; PARAPLATIN)

  • Carboxypeptidase G2 (a methotrexate-cleaving enzyme used to reduce methotrexate in plasma)

  • Chlorambucil (LEUKERAN)

  • Cisplatin (PLATINOL, others)

  • Cladribine (2-chlorodeoxyadenosine, 2-CdA; LEUSTATIN, others)

  • Clofarabine (2-chloro-2′-fluoro-arabinosyladenine)

  • Cyclophosphamide (LYOPHILIZED CYTOXAN, others)

  • Cytarabine (1-β-D-arabinofuranosylcytosine, cytosine arabinoside, Ara-C; CYTOSAR-U, TARABINE PFS, DEPOCYT, others)

  • Dacarbazine (DTIC; DTIC-DOME)

  • Dactinomycin (actinomycin D; COSMEGEN)

  • Daunorubicin (daunomycin, rubidomycin; CERUBIDINE, others)

  • Decitabine (2′-deoxy-5-azacytidine)

  • Docetaxel (TAXOTERE)

  • Doxorubicin (ADRIAMYCIN)

  • Epirubicin (ELLENCE, others)

  • Estramustine (EMCYT)

  • Etoposide (VP-16-213; VEPESID, others)

  • Floxuridine (FUdR, fluorodeoxyuridine; FUDR, others)

  • Fludarabine phosphate (FLUDARA, OFORTA)

  • Gemcitabine (2′,2′-difluorodeoxycytidine; dFdC, GEMZAR)

  • High-dose methotrexate with leucovorin rescue (HDM-L)

  • Hydroxyurea (HU; HYDREA, DROXIA, others)

  • Idarubicin (IDAMYCIN PFS)

  • Ifosfamide (IFEX, others)

  • Irinotecan (CPT-11; CAMPTOSAR, others)

  • Ixabepilone (IXEMPRA)

  • L-asparaginase (L-ASP; ELSPAR)

  • Leucovorin (folinic acid, citrovorum factor, 5-formyltetrahydrofolate, N5-formyl FH4)

  • Lometrexol

  • Lomustine (CCNU; CeeNU)

  • Mechlorethamine HCl (MUSTARGEN)

  • Melphalan (ALKERAN)

  • Methotrexate (amethopterin; RHEUMATREX, TREXALL, others)

  • Mitomycin (mitomycin-C; MUTAMYCIN, others)

  • Mitotane (o,p’-DDD)

  • Mitoxantrone (NOVANTRONE, others)

  • Nab-paclitaxel (ABRAXANE)

  • Nelarabine (6-methoxy-arabinosyl-guanine)

  • Oxaliplatin (ELOXATIN)

  • Paclitaxel (TAXOL, others)

  • Pegaspargase (PEG-l-Asparaginase; ONCASPAR)

  • Pemetrexed (MTA; ALIMTA)

  • Pentostatin (2’-deoxycoformycin)

  • Pralatrexate (FOLOTYN)

  • Procarbazine (MATULANE)

  • Raltitrexed (TOMUDEX)

  • Romidepsin (depsipeptide, FK228; ISTODAX)

  • Semustine (methyl-CCNU)

  • Streptozocin (streptozotocin; ZANOSAR)

  • Temozolomide (TEMODAR)

  • Teniposide (VM-26; VUMON)

  • Thiotepa (triethylenethiophosphoramide; THIOPLEX, others)

  • Topotecan (HYCAMTIN)

  • Trabectedin (YONDELIS)—not currently ...

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