Drug | Pharmacologic Features | Major Indications | Associated Toxicoses | Route of Administration |
---|---|---|---|---|
Alkylating Agents | ||||
Cyclophosphamide | Prodrug requiring hepatic metabolism for activation, relatively sparing of megakaryocytes and hematopoietic stem cells; bifunctional alkylator, nitrogen mustard class | Lymphoma, mammary adenocarcinoma and other carcinomas, sarcomas, lymphoid leukemias, metronomic chemotherapy | Nausea, vomiting, moderate to severe myelosuppression, sterile hemorrhagic cystitis | PO, IV |
Ifosfamide | Analogue of cyclophosphamide; requires hepatic biotransformation for activation; bifunctional alkylator, nitrogen mustard class | Various sarcomas, particularly leiomyosarcoma | Nausea, vomiting, myelosuppression, sterile hemorrhagic cystitis, possible nephrotoxicosis | IV with saline diuresis and mesna to prevent hemorrhagic cystitis |
Chlorambucil | Does not require hepatic metabolism for activation; bifunctional alkylator; considered slow-acting alkylating agent, nitrogen mustard class | Chronic lymphocytic leukemia, small-cell lymphoma, metronomic chemotherapy | Nausea, vomiting, diarrhea, mild to moderate myelosuppression, cumulative thrombocytopenia | PO |
Melphalan | Does not require biotransformation for activation; bifunctional alkylator, nitrogen mustard class | Multiple myeloma, anal gland carcinoma | Nausea, vomiting, diarrhea, anorexia, moderate myelosuppression (may be more myelosuppressive in cats) | PO, IV |
Lomustine (CCNUa) | Highly lipid soluble and able to cross blood-brain barrier; bifunctional alkylating agent, nitrosourea class | Lymphoma, mast cell tumors, histiocytic sarcomas, CNS neoplasms, multiple myeloma | Nausea, vomiting, diarrhea, moderate to severe myelosuppression (may be delayed for 4–6 wk, particularly in cats), hepatotoxicosis (dogs), nephrotoxicosis, cumulative pulmonary toxicosis | PO |
Streptozotocin | High affinity for pancreatic beta cells; nitrosourea class; also classified as antitumor antimicrobial (Streptomyces product) | Insulinoma | Severe, potentially fatal nephrotoxicosis (if administered without diuresis) and hepatotoxicosis, nausea (immediate and delayed), vomiting, diarrhea, mild myelosuppression, diabetes mellitus | IV infusion with diuresis |
Dacarbazine | Requires hepatic biotransformation for activation; monofunctional alkylator, nonclassical class | Lymphoma, sarcomas, melanoma (often combined with anthracycline) | Severe acute nausea, vomiting, diarrhea, phlebitis, moderate myelosuppression, hepatotoxicosis, pleural effusion in cats (anecdotal) | IV infusion |
Temozolomide | Imidazotetrazine derivative of dacarbazine; able to cross blood-brain barrier; monofunctional alkylator, nonclassical class | Lymphoma, sarcomas, melanoma, gliomas and other brain tumors | Nausea, vomiting, diarrhea, mild to moderate myelosuppression | PO |
Cisplatin | Platinum molecule with two chloride ligands and two ammonium ions; causes methylation with some bifunctional alkylating activity; nonclassical alkylator class | Osteosarcoma, carcinomas, mesothelioma, malignant effusions (intracavitary) | Intense nausea, vomiting, diarrhea, mild to moderate myelosuppression, potentially fatal nephrotoxicosis if administered without diuresis, anaphylaxis, ototoxicosis, peripheral neuropathy; cannot be administered to cats (fulminant pulmonary edema) | IV or intracavitary, with vigorous saline diuresis; intralesional (including beads in horses) |
Carboplatin | Analogue of cisplatin; monofunctional and bifunctional alkylator, nonclassical alkylator class | Osteosarcoma, carcinomas | Mild nausea, vomiting, diarrhea, moderate to severe myelosuppression, rare ototoxicosis/deafness; safe for cats | IV |
Antimetabolites | ||||
Rabacfosadine | Guanine analogue; inhibits DNA polymerases and thereby DNA synthesis | Lymphoma (FDA approved for dogs) | Nausea, vomiting, mild to moderate myelosuppression, hepatoxicosis and possibly nephrotoxicosis, dermatopathy, cumulative pulmonary fibrosis (may be idiosyncratic) | IV infusion |
Cytarabine | Pyrimidine analogue; incorporates into DNA, resulting in steric hindrance and inhibition of DNA synthesis | Lymphoma (including CNS), leukemias, CNS inflammatory disease; no activity in solid tumors | Nausea, vomiting, moderate myelosuppression, nephrotoxicosis, hepatotoxicosis | IV infusion, SC |
5-Fluorouracil | Pyrimidine analogue; interferes with DNA synthesis and incorporates into RNA; binds thymidylate synthase | Carcinomas, particularly GI and cutaneous (systemic); cutaneous carcinomas, particularly squamous cell carcinomas (topical) | Systemic: nausea, vomiting, moderate myelosuppression, GI ulceration, neurotoxicosis, hepatotoxicosis Topical: local irritation, pain, hyperpigmentation Cannot be administered to cats (fatal neurotoxicosis) | IV; topical (horses) |
Gemcitabine | Pyrimidine analogue; incorporates into DNA, resulting in steric hindrance and inhibition of DNA synthesis | Limited efficacy observed in lymphoma and various carcinomas | Mild nausea, vomiting, mild to moderate myelosuppression, pulmonary toxicosis, nephrotoxicosis | IV |
Methotrexate | Folic acid analogue; inhibits DNA synthesis and repair by blocking the formation of tetrahydrofolate | Lymphoma, immune disorders | Nausea, vomiting, moderate myelosuppression, GI ulceration, hepatotoxicosis, pulmonary toxicosis | IV, PO, intrathecal |
Antineoplastic Antimicrobials | ||||
Doxorubicin | Disrupts DNA helical structure and template function: directly alkylates DNA; inhibits DNA and RNA polymerases and helicase, promotes cleavage of DNA by topoisomerase II beta, generates reactive oxygen species, and interacts with the plasma membrane; anthracycline antimicrobial | Lymphoma, leukemias, multiple myeloma, osteosarcoma, hemangiosarcoma, and various other sarcomas and carcinomas | Nausea, vomiting, moderate myelosuppression, hemorrhagic colitis, severe cutaneous reactions if extravasated; red urine (not hematuria), transient ECG changes and arrhythmias, nephrotoxicosis, anaphylactoid reactions; cumulative dose-related cardiomyopathy in dogs; cumulative nephrotoxicosis in cats | IV infusion over 15–30 min |
Mitoxantrone | Synthetic anthracenedione derivative of doxorubicin; promotes cleavage, aggregation, oxidation, and strand breakage of DNA | Lymphoma, various carcinomas; often substituted for doxorubicin when risk of cardiotoxicosis is a concern | Nausea, vomiting, moderate to severe myelosuppression, diarrhea, bluish discoloration to sclera; adverse effects less severe than for others in this group | IV |
Bleomycin | Mixture of glycopeptides; generates oxygen radicals that cause cleavage and fragmentation of DNA | Carcinomas, acanthomatous ameloblastoma, malignant effusions | Nausea, vomiting, myelosuppression, fever, allergic reactions including anaphylaxis, hyperpigmentation, skin ulceration, pneumonitis, pulmonary fibrosis | SC, intralesions (odontogenic tumors), intracavitary |
Mitotic Inhibitors | ||||
Vinblastine | Vinca alkaloid | Lymphoma and leukemias, mast cell tumors, transitional cell carcinoma | Mild nausea, vomiting, moderate to severe myelosuppression, neurotoxicosis with high doses, extravasation reactions, inappropriate secretion of antidiuretic hormone | IV |
Vincristine | Vinca alkaloid derived from periwinkle plant | Lymphoma and leukemias, transmissible venereal cell tumors, various sarcomas | Mild to moderate nausea, vomiting, mild to moderate myelosuppression, severe tissue reaction if extravasated, cumulative peripheral neuropathy, constipation, paralytic ileus, inappropriate secretion of antidiuretic hormone | IV |
Vinorelbine | Synthetic vinca alkaloid | Primary lung tumors, limited efficacy in mast cell tumors | Mild nausea, vomiting, myelosuppression | IV |
Paclitaxel | Taxane | Mammary carcinomas, squamous cell carcinomas | Myelosuppression, nausea, vomiting, hypersensitivity (when polyethoxylated castor oil base is used as vehicle) requiring prophylaxis and often dose limiting | IV |
Hormones | ||||
Prednisone | Glucocorticoid steroid; lympholytic: induces apoptosis and inhibits mitosis in lymphocytes | Lymphoid malignancies (lymphoma, leukemias, plasmacytoma, multiple myeloma), mast cell tumors; palliative treatment of brain tumors | Polyuria/polydipsia, polyphagia, GI ulceration, protein catabolism, delayed wound healing, suppression of hypothalamic-pituitary-adrenal axis, immunosuppression, peripheral insulin resistance | PO |
Miscellaneous | ||||
l-Asparaginase | Enzyme that cleaves asparagine to deplete circulating concentrations of this amino acid; G1 phase–specific drug based on inhibition of protein synthesis in cells lacking sufficient concentrations of asparagine synthetase (eg, malignant immature lymphocytes) | Acute lymphoid leukemias and lymphoma | Hypersensitivity reactions, anaphylaxis especially after repeated doses, alteration in coagulation parameters, hepatotoxicosis, potential inhibition of immune responsiveness (B and T cells) | SC, IM |
Mitotane (o,p′DDD) | Derivative of the pesticide DDT; has selective direct cytotoxic effects on adrenal cortical cells; inhibits steroid production | Pituitary-dependent hyperadrenocorticism, adrenal cortical tumors | Nausea, vomiting, anorexia, diarrhea, adrenal insufficiency, CNS depression, dermatitis | PO |
Hydroxyurea | Inhibits conversion of ribonucleotides to deoxyribonucleotides by inhibiting ribonucleoside diphosphate reductase | Polycythemia vera, granulocytic and basophilic leukemia, essential thrombocythemia; investigational for meningiomas | Nausea, vomiting, myelosuppression, alopecia, sloughing of claws, dysuria, potential hepatotoxicosis | PO |
Procarbazine | Mechanism is unclear; inhibits DNA, RNA, and protein synthesis, likely through alkylation; crosses blood-brain barrier | Lymphoma, as part of MOPPb chemotherapy protocol; brain tumors and inflammatory lesions | Nausea, vomiting, myelosuppression, diarrhea | PO |
aCCNU stands for the chemical name of lomustine: 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. | ||||
bThe acronym MOPP is derived from the drug names Mustargen (chlormethine), Oncovin (vincristine), procarbazine, and prednisone. |