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Chapter 45: Cancer Chemotherapy and Cytotoxic Agents

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 ...

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