II. Medications: Traditional Chemotherapy
- Background
- Traditional Chemotherapy targets cells that divide frequently
- Cancer cells typically divide more rapidly than normal cells
- Limits cell proliferation
- However, normal cells (e.g. gastrointestinal mucosa) also divide frequently, resulting in adverse effects
- Mechanisms of traditional Chemotherapy activity
- DNA cross-linking
- Alkylating DNA bases
- DNA or RNA base analog mimics
- Intercalation between DNA base pairs
- Traditional Chemotherapy targets cells that divide frequently
- Traditional Chemotherapy Drug Classes
- Alkylating Agent
- Replicating cells and rapidly growing cells are most susceptible to agents (rbc, GI cells, hair cells)
- Exert cytotoxic effects via transfer of unstable alkyl group
- DNA alkylation (key to cellular lethality, esp. DNA cross linking)
- Chemically react with other cellular constituents (e.g. Proteins)
- Not Cell Cycle specific
- Alkylating Agent sub-classes
- Nitrogen Mustard Antineoplastic Compounds (e.g. Bendamustine, Chlorambucil, Cyclophosphamide)
- Nitrosourea Compounds (e.g. Carmustine, Lomustine, Semustine, Streptozocin)
- Aziridines (e.g. Thiotepa, Triethylenemelamine)
- Mesylate (e.g. Busulfan)
- Triazene Antineoplastic (e.g. Procarbazine, Dacarbazine, Temozolamide)
- Platinum Analogs (e.g. Carboplatin, Cisplatin, Oxaliplatin)
- Miscellaneous Alkylating Agents (e.g. Hexamethylmelamine, Trabectedin)
- Antimetabolite Chemotherapy
- Analogs block DNA, RNA or Protein synthesis, suppressing cancer cell expression, growth and replication
- Purine Analogs (e.g. Azathioprine, Cladribine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine)
- Purine Analogs, resembling adenine or guanine, and incorporate into DNA
- Result in DNA cross-linking and inhibition of synthesis and repair of DNA
- Pyrimidine Analogs (e.g. Capecitabine, Floxuridine, Fluorouracil, Trifluridine)
- Pyrimidine Analogs, resembling cytosine, uracil or thymine, and incorporate into DNA and RNA
- Inhibits DNA and RNA synthesis
- Cytidine Analogs (e.g. Azacitidine, Cytarabine, Decitabine, Gemcitabine)
- Antineoplastic, PyrimidineNucleoside analogs of cytidine
- By binding DNA at cytidine binding sites, these analogs block DNA methylation
- Folic Acid Antagonist (e.g. Methotrexate, Pemetrexed, Pralatrexate)
- Folic Acid analogs that resemble its structure, binding Folate-dependent enzymes, and block their activity
- As an example, inhibition of dihydrofolate reductase results in a failed synthesis of Tetrahydrofolate (FH4)
- Result in decreased DNA, RNA and Protein synthesis
- Histone Deacetylase Inhibitor (e.g. Belinostat, Romidepsin, Panobinostat, Vorinostat)
- Histones are the spools around which DNA are wrapped, and which play a role in gene expression
- Cancers may be facilitated by abnormally expressed genes in specific histone regions
- HDAC Inhibitors block histone deacetylase
- Histone deacetylase is an enzyme that catalyzes removal of acetyl groups from core histones
- Results in hyperacetylation of histones, suppressing gene expression and cell differentiation
- Histones are the spools around which DNA are wrapped, and which play a role in gene expression
- Hormonally Active Chemotherapy
- Hormone Analogs (naturally occurring or derivatives)
- Corticosteroids
- Indicated in lymphoid malignancy
- Somatostatin Analogs (e.g. Octreotide, Lanreotide)
- Indicated in GI neuroendocrine tumors, Carcinoid Syndrome, Merkel Cell carcinoma
- Progestins (e.g. Megestrol acetate, Medroxyprogesterone acetate)
- Conjugates (novel, hormonal agents conjugated to a cytotoxic agent, e.g. Estramustine)
- Corticosteroids
- Hormone Synthesis Inhibitors
- Used in Prostate Cancer or Breast Cancer
- Gonadotropin-Releasing Hormone Agonists (e.g. Leuprolide, Goserelin, Histrelin)
- Gonadotropin-Releasing Hormone Antagonists (e.g. Degarelix, Relugolix)
- Androgen Synthesis Inhibitor (e.g. Abiraterone)
- Aromatase Inhibitors (e.g. Letrozole, Anastrozole, Exemestane, Aminoglutethimide)
- Hormone Receptor Inhibitors
- Used in Prostate Cancer or Breast Cancer
- Selective Estrogen Receptor Modulators (e.g. Tamoxifen, Raloxifene, Toremifene, Fulvestrant)
- Antiandrogens - Non-Steroidal Testosterone Receptor Antagonists (for Prostate Cancer)
- First Generation (e.g. Flutamide, Bicalutamide, Nilutamide)
- Second Generation (e.g. Apalutamide, Darolutamide, Enzalutamide, Proxalutamide)
- Hormone Analogs (naturally occurring or derivatives)
- Mitotic Inhibitor Chemotherapy (block Mitosis)
- Includes Plant Alkaloid Chemotherapy (e.g. Vinca Alkaloids, Podophyllotoxins)
- Vinca Alkaloids (e.g. Vinblastine, Vincristine, Vinorelbine)
- Taxanes (Paclitaxel, Taxotere, Cabazitaxel)
- Topoisomerase 1 Inhibitors (e.g. Topotecan, Irinotecan)
- Topoisomerase 2 Inhibitors (e.g. Anthracyclines, Etoposide, Teniposide)
- Antibiotic Chemotherapy
- S-Phase Specific (Synthesis Phase)
- Dactinomycin (Actinomycin D, Cosmegen)
- Anthracyclines (e.g. Daunorubicin, Doxorubicin, Idarubicin, Epirubicin, Valrubicin)
- G2 Cell Phase and M-Phase (Mitosis Phase) Specific
- Not Cell Phase Specific
- Plicamycin (Mithramycin)
- Mitomycin (Mitomycin C, Mitocin-C, Mutamycin)
- Mitoxantrone (Novantrone)
- S-Phase Specific (Synthesis Phase)
- Alkylating Agent
- Miscellaneous Traditional Chemotherapy
- Amsacrine
- Arsenic Trioxide
- Asparaginase
- Hydoxyurea
- Mitoxantrone
- Mitotane (Lysodren)
- Quinacrine
- Tretinoin
III. Medications: Targeted Cancer Therapy
- See Targeted Cancer Therapy
- See Immuno-Chemotherapy
- See Monoclonal Antibody-Mediated Chemotherapy
- See Immune Checkpoint Inhibitor
- See CAR T-Cell Therapy
- See Small Molecule Inhibitor-Mediated Chemotherapy
-
Monoclonal Antibody-Mediated Chemotherapy
- Example: Rituximab (Rituxan), used in Non-Hodgkin's Lymphoma and Rheumatoid Arthritis
- Monoclonal antibodies act at targeted cells via oncogene downregulation or tumor cell flagging for destruction
- Initially targeted to CD20 on immune cells to treat Lymphoma and Leukemia, later for Autoimmune Disease
- Targeted to solid tumors (e.g. Breast Cancer, Lung Cancer, Colon Cancer) , binding extracellular Ligands and receptors
- xHER2 (e.g. Trastuzumab) have been very effective in HER2 positive Breast Cancer
- xEGFR (e.g. Cetuximab) have been effective in metastatic Colorectal Cancer (without RAS mutation)
-
Small Molecule Inhibitor-Mediated Chemotherapy
- Example: Imatinib (Gleevec)
- Primarily oral agents (contrast with other Chemotherapy which is primarily intravenous)
- Targeted to Protein kinases (esp. Tyrosine Kinase), interfering with EGFR, HER2-neu and VEGF
- Small molecules that principally act intracellularly, with less Specificity than monoclonal antibodies
- Small molecules also effect healthy tissue, and therefore have systemic effects
- Widely variable efficacy depending on tumor type
-
Antibody-Drug Conjugates (ADC)
- Example: Trastuzumab emtansine (T-DM1, trade name: Kadcyla) for refractory, advanced HER2+ Breast Cancer
- Monoclonal Antibody bound to cytotoxic Chemotherapy is specifically directed at tumor cells
- Local destruction of normal cells in vicinity of tageted tumor cells
- Systemic effects include Fatigue, Nausea, Peripheral Neuropathy and Thrombocytopenia
- Active Immunotherapy (tumor cell specific targeting)
- Monoclonal Antibody-Mediated Chemotherapy
- CAR T-Cell Therapy
- Oncologic Vaccines (e.g. sipuleucel-T, Prostate Cancer)
- Passive Immunotherapy (Immuno-modulators)
- Cytokines
- Immune Checkpoint Inhibitors
- Counter tumor cell generated Immune Suppression by blocking their activity on T-Cells
- Immune Checkpoint Inhibitors are very effective in mestatatic Non-Small Cell Lung Cancer
- Example: Pembrolizumab (Keytruda) targets Programmed Cell Death Protein 1 (PD-1)
- Example: Atezolizumab (Tecentriq) targets Programmed Death Ligand-1 (PDL-1)
- Example: Ipilimumab (Yervoy) targets Cytotoxic T Lymphocyte Associated-4 (CTLA-4)
IV. Adverse Effects
- See specific drugs and their classes
- See Cancer Symptom (includes Oncologic Emergencies)
- See Cytokine Release Syndrome
- See Tumor Lysis Syndrome
- See Neutropenic Fever
V. Management: General
- See Cancer Symptom
-
Exercise encouraged following high dose Chemotherapy
- Safe
- Prevents deconditioning
- Decreases toxic side effects of Chemotherapy
- Dimeo (1997) Blood 90:3390-4 [PubMed]
VI. Management: Extravasation of agents from IV
- Practice vigilent prevention
- Findings: Onset with hours of Chemotherapy
- Early: Pain, local erythema and swelling
- Later: Blanching, Blistering, discoloration and tissue necrosis
- Management: Early recognition and treatment is critical
- Immediately stop any infusion
- Leave cannula in place until management plan is established
- Apply ice to area
- Do not compress area
- Use antidotes if available
- Urgent Consultations with Oncology and Surgery
- Debridement with skin grafting may be needed
- Complications
- Scarring
- Contractures
- Amputation
- References
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Related Studies
| Definition (NDFRT) | NOTE: Includes hormones (AN500) which are exclusively used as antineoplastics (e.g.,tamoxifen). Excludes other hormones (HS000). |
| Definition (NCI) | A substance that inhibits the maturation, growth or spread of tumor cells. |
| Definition (NCI_NCI-GLOSS) | A drug used to treat cancer. |
| Definition (MSH) | Substances that inhibit or prevent the proliferation of NEOPLASMS. |
| Definition (PSY) | Drugs used in the prevention of the development, maturation, or spread of neoplastic cells. |
| Definition (CSP) | agent that inhibits or prevents the development or proliferation of neoplasms. |
| Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
| MSH | D000970 |
| SnomedCT | 327392000, 27867009, 372688009 |
| English | Antineoplastic Drugs, Agents, Antineoplastic, Antineoplastics, Drugs, Antineoplastic, ANTINEOPL AGENTS, ANTINEOPLASTICS, Antitumor Agents, Agents, Antitumor, Antitumor Drugs, Drugs, Antitumor, chemotherapeutics (medication), antineoplastic agents, chemotherapeutics, chemotherapeutic agents, Other antineoplastic agents, Antineoplastic Agent [TC], Antineoplastic Agent, [AN000] ANTINEOPLASTICS, agents antineoplastics, antineoplastic agent, agents antineoplastic, antineoplastics, antineoplastic drug, anti-neoplastic agents, antineoplastic drugs, Drug, Chemotherapeutic Anticancer, Agents, Chemotherapeutic Anticancer, Chemotherapy Agents, Cancer, Drugs, Cancer Chemotherapy, Chemotherapeutic Anticancer Drug, Agents, Cancer Chemotherapy, Chemotherapy Drugs, Cancer, Chemotherapeutic Anticancer Agents, Cancer Chemotherapy Agents, Agents, Anticancer, Cancer Chemotherapy Drugs, Anticancer Agents, ANTINEOPLASTIC AGENTS, Other antineoplastic agents (product), Antineoplastic agents, chemotherapeutic agent, Antineoplastic, Antineoplastic agent (product), Antineoplastic agent (substance), Antineoplastic agent, antineoplastic, miscellaneous antineoplastic, antitumor agent, Antineoplastic agent, NOS, Other antineoplastic agents (substance), Cancer Drug, Chemotherapeutic Agents, Neoplastic Disease, Anti-Cancer Agents, Anti-Tumor Agents, Anti-Tumor Drugs, Tumor-Specific Treatment Agents, Antiproliferative Agents, Antiproliferative Drugs, Antineoplastic Agents |
| French | Agents anticancéreux, Médicaments antinéoplasiques, Agents antinéoplasiques, Agents antitumoraux, Antitumoraux, Médicaments antitumoraux, Anticancéreux, Antinéoplasiques, Médicaments anticancéreux |
| Swedish | Cellgifter |
| Czech | antitumorózní látky, protinádorové látky |
| Finnish | Antineoplastiset aineet |
| Italian | Farmaci antineoplastici, Antineoplastici |
| Russian | PROTIVOOPUKHOLEVYE SREDSTVA IMMUNODEPRESSIVNYE, PROTIVOOPUKHOLEVYE I IMMUNODEPRESSIVNYE SREDSTVA, PROTIVOOPUKHOLEVYE SREDSTVA, ПРОТИВООПУХОЛЕВЫЕ СРЕДСТВА, ПРОТИВООПУХОЛЕВЫЕ И ИММУНОДЕПРЕССИВНЫЕ СРЕДСТВА, ПРОТИВООПУХОЛЕВЫЕ СРЕДСТВА ИММУНОДЕПРЕССИВНЫЕ |
| Japanese | 白血病治療剤, 抗癌剤, 抗癌薬, 抗腫瘍物質, 癌化学療法薬, 抗悪性腫瘍薬, 癌化学療法薬剤, 抗新生物薬, 抗白血病剤, 制癌剤, 制がん剤, 制癌物質, 癌治療剤, 抗がん薬, 抗癌薬剤, 抗白血病薬, 白血病治療薬, 抗がん剤, 制癌薬, 抗悪性腫瘍剤, 抗腫瘍性物質, 抗腫瘍薬, 癌化学療法剤, 抗腫瘍剤 |
| Croatian | ANTITUMORSKA SREDSTVA |
| Polish | Cytostatyki przeciwnowotworowe, Leki przeciwnowotworowe |
| Spanish | Antineoplásicos, otros agentes antineoplásicos (producto), otros agentes antineoplásicos, Fármacos Antineoplásicos, Agentes Antineoplásicos, agente antineoplásico (producto), agente antineoplásico (sustancia), agente antineoplásico |
| Portuguese | Agentes Antineoplásicos, Fármacos Antineoplásicos, Antineoplásicos |
| German | Antitumormittel, Antineoplastika |
Ontology: Pharmacotherapy (C0013216)
| Definition (MSH) | The use of DRUGS to treat a DISEASE or its symptoms. One example is the use of ANTINEOPLASTIC AGENTS to treat CANCER. |
| Definition (NCI) | Treatment of disease through the use of drugs. |
| Definition (NCI_NCI-GLOSS) | Treatment with any substance, other than food, that is used to prevent, diagnose, treat, or relieve symptoms of a disease or abnormal condition. |
| Definition (PSY) | Mandatory term applied to studies dealing with the use of drugs in the clinical treatment of diseases or psychological disorders. Used for human or animal populations. For the use of drugs in non-clinical contexts, use PHARMACOLOGY or PSYCHOPHARMACOLOGY. |
| Definition (HL7V3.0) | <p>The introduction of a drug into a subject with the intention of altering its biologic state with the intent of improving its health status.</p> |
| Concepts | Therapeutic or Preventive Procedure (T061) |
| MSH | D004358 |
| SnomedCT | 416608005, 182915007, 182831000, 266814004, 151196004 |
| HL7 | DRUG |
| English | Drug Therapies, Drug Therapy, Pharmacotherapies, Pharmacotherapy, Therapies, Drug, Therapy, Drug, pharmacotherapy, Drug therapy NOS, Pharmacological Treatment, Treatment With Medication, PHARMACOTHER, DRUG THER, THER DRUG, DT - Drug therapy, drug treatment (drug therapy), drugs therapies, medication therapy, drug therapies, pharmacotherapies, therapy medication, drug therapy, medications therapy, pharmacotherapeutics, drug therapy treatment, Medication therapy, Drug therapy NOS (procedure), Therapy (Drug), Pharmacological Treatments, Drug therapy, Drug therapy (procedure) |
| French | Chimiothérapie, Traitement médicamenteux, Traitement par des médicaments, Thérapie médicamenteuse, Thérapie par des médicaments, Pharmacothérapie |
| Swedish | Läkemedelsterapi |
| Japanese | ﾔｸﾌﾞﾂﾘｮｳﾎｳ, 化学療法, 薬物療法, 投薬, 薬物治療 |
| Czech | farmakoterapie, Léková terapie, chemoterapie, terapie léky |
| Finnish | Lääkehoito |
| Italian | Chemioterapia, Farmacoterapia, Terapia farmacologica |
| Russian | KHIMIOTERAPIIA, FARMAKOTERAPIIA, LEKARSTVENNAIA TERAPIIA, ЛЕКАРСТВЕННАЯ ТЕРАПИЯ, ФАРМАКОТЕРАПИЯ, ХИМИОТЕРАПИЯ |
| Croatian | FARMAKOTERAPIJA |
| Spanish | tratamiento farmacológico, tratamiento farmacológico (procedimiento), farmacoterapia, farmacoterapia, SAI (procedimiento), farmacoterapia, SAI, quimioterapia, farmacoterapia (procedimiento), Drug therapy NOS, Tratamiento farmacológico, Farmacoterapia, Quimioterapia |
| Polish | Farmakoterapia, Leczenie farmakologiczne |
| Hungarian | Gyógyszeres kezelés |
| Norwegian | Kjemoterapi, Farmakoterapi, Medikamentell behandling |
| Portuguese | Tratamento Medicamentoso, Tratamento farmacológico, Farmacoterapia, Quimioterapia |
| Dutch | geneesmiddelentherapie, Chemotherapie, Farmacotherapie, Therapie, medicamenteuze |
| German | Therapie mit Medikamenten, Arzneimitteltherapie, Chemotherapie, Pharmakotherapie, Medikamentöse Therapie, Therapie, medikamentöse |
Ontology: Chemotherapeutic agent (C0729502)
| Concepts | Pharmacologic Substance (T121) |
| SnomedCT | 312059006 |
| English | chemotherapeutic agent, agents chemotherapeutic, Chemotherapeutic agent (product), Chemotherapeutic agent (substance), Chemotherapeutic agent |
| Spanish | agente quimioterapéutico (producto), agente quimioterapéutico |
