Hematology and Oncology Principles of Cancer Therapy Modalities of Cancer Therapy
MERCK MANUALS
FOR HEALTHCARE ONLINE MEDICAL LIBRARY PROFESSIONALS
COMMONLY USED ANTINEOPLASTIC DRUGS
DRUG MECHANISM OF ACTION COMMONLY RESPONSIVE TUMORS TOXICITY AND COMMENTS
ANTIMETABOLITES: FOLATE Methotrexate
ANTAGONISTS
Binds to dihydrofolate Acute lymphocytic reductase and interleukemia feres with thymidyl- Choriocarcinoma ate synthesis (women) Head and neck cancer Malignant lymphoma Osteogenic sarcoma Ovarian cancer
Mucosal ulceration Bone marrow suppression Increased toxicity with impaired renal function or ascitic fluid (with pooling of drug) Reversal of toxicity with leucovorin rescue at 24 h (10–20 mg q 6 h 10 doses) Bone marrow suppression Mucosal ulceration
Pemetrexed
Inhibits thymidylate synthase
Lung cancer Mesothelioma Ovarian cancer
ANTIMETABOLITES: PURINE Cladribine Clofarabine
ANTAGONISTS
Inhibits ribonucleotide Leukemia reductase Lymphoma Inhibits DNA synthesis
Myelosuppression Immunosuppression
Myelosuppression Acute lymphocytic leukemia refractory to Immunosuppression at least 2 prior chemotherapy regimens Nausea Diarrhea Myelosuppression Immunosuppression Autoimmune reactions Myelosuppression Immunosuppression Myelosuppression Immunosuppression Myelosuppression Immunosuppression Nausea Vomiting
Fludarabine
6-Mercaptopurine Nelarabine Pentostatin
Leukemia Terminates DNA synthesis and Lymphoma inhibits ribonucleotide reductase Blocks de novo purine Acute leukemia synthesis Inhibits DNA synthesis Inhibits DNA synthesis Leukemia Lymphoma Leukemia
ANTIMETABOLITES: PYRIMIDINE Capecitabine
ANTAGONISTS
Inhibits thymidylate synthase
Breast cancer GI tumors
Mucositis Alopecia Myelosuppression Diarrhea Vomiting Hand or foot tenderness Ulceration
THE
SECTION SUBJECT TOPIC
Hematology and Oncology Principles of Cancer Therapy Modalities of Cancer Therapy
MERCK MANUALS
FOR HEALTHCARE ONLINE MEDICAL LIBRARY PROFESSIONALS
COMMONLY USED ANTINEOPLASTIC DRUGS—Continued
DRUG MECHANISM OF ACTION COMMONLY RESPONSIVE TUMORS TOXICITY AND COMMENTS
Cytarabine
Terminates chain when incorporated into DNA
Myelosuppression Acute leukemia (especially nonlymphocytic) Nausea Lymphoma Vomiting Cerebellar toxicity (at high doses) Conjunctival toxicity (at high doses) Rash Breast cancer GI tumors Mucositis Alopecia Myelosuppression Diarrhea Vomiting Myelosuppression Hemolytic-uremic syndrome Myelosuppression
5-Fluorouracil
Inhibits thymidylate synthase
Gemcitabine
Hydroxyurea BIOLOGIC
Terminates chain when incorporated into DNA and inhibits ribonucleotide reductase Inhibits ribonucleotide reductase
Bladder cancer Lung cancer Pancreatic cancer Chronic myelocytic leukemia
BLEOMYCINS Bleomycin Causes DNA strands to break Lymphoma Squamous cell cancer Testicular cancer Anaphylaxis Chills and fever Rash Pulmonary fibrosis at dosage > 200 mg/m2 Requires renal excretion Myelosuppression Pulmonary toxicity (fibrosis) Myelosuppression Pulmonary toxicity (delayed) Renal toxicity
DNA ALKYLATING AGENTS: NITROSOUREAS Carmustine Alkylates DNA with Brain tumors restricted uncoiling Lymphoma and replication of strands Lomustine Same as for carmustine Brain tumors (astrocytoma, glioblastoma)
THE
SECTION SUBJECT TOPIC
Hematology and Oncology Principles of Cancer Therapy Modalities of Cancer Therapy
MERCK MANUALS
FOR HEALTHCARE ONLINE MEDICAL LIBRARY PROFESSIONALS
COMMONLY USED ANTINEOPLASTIC DRUGS—Continued
DRUG MECHANISM OF ACTION COMMONLY RESPONSIVE TUMORS TOXICITY AND COMMENTS
DNA CROSS-LINKING DRUGS AND ALKYLATING AGENTS Breast cancer Bendamustine Form adducts with DNA, causing DNA Chronic lymphocytic Chlorambucil strands to break leukemia CyclophosphaGliomas mide Hodgkin lymphoma Ifosfamide Lymphoma Mechlorethamine Multiple myeloma (nitrogen Small cell lung cancer mustard) Testicular cancer Melphalan
Alopecia with high IV dosage Nausea Vomiting Myelosuppression Hemorrhagic cystitis (especially with cyclophosphamide and ifosfamide), which can be ameliorated with mesna Mutagenesis Secondary leukemias Aspermia Permanent sterility (possible) Neutropenia Nausea Vomiting Secondary leukemias Neutropenia Nausea Vomiting Secondary leukemias Acute anaphylaxis Hyperthermia Pancreatitis Hyperglycemia Hypofibrinogenemia Decreased libido Hot flushes Gynecomastia Nausea Vomiting Constipation Diarrhea Abdominal pain Headache Back pain Hot flushes Pharyngitis
Dacarbazine Form adducts with DNA Temozolomide
Melanoma Malignant glioma
Procarbazine
Unclear
Hodgkin lymphoma
ENZYMES Asparaginase
Depletes asparagine, on which leukemic cells depend
Acute lymphocytic leukemia
HORMONES Bicalutamide Flutamide Fulvestrant
Bind to androgen receptor
Prostate cancer
Binds to estrogen receptor
Metastatic breast cancer
THE
SECTION SUBJECT TOPIC
Hematology and Oncology Principles of Cancer Therapy Modalities of Cancer Therapy
MERCK MANUALS
FOR HEALTHCARE ONLINE MEDICAL LIBRARY PROFESSIONALS
COMMONLY USED ANTINEOPLASTIC DRUGS—Continued
DRUG MECHANISM OF ACTION COMMONLY RESPONSIVE TUMORS TOXICITY AND COMMENTS
Leuprolide acetate
Inhibits gonadotropin secretion
Prostate cancer
Hot flushes Decreased libido Irritation at injection site Weight gain Fluid retention Hot flushes Hypercalcemia Deep venous thrombosis Osteoporosis Hot flushes
Megestrol acetate Tamoxifen
Progesterone agonist Binds to estrogen receptor
Breast cancer Endometrial cancer Breast cancer
HORMONES: AROMATASE INHIBITORS Anastrozole Block conversion of Breast cancer androgen to estrogen Exemestane Letrozole MONOCLONAL Alemtuzumab Bevacizumab
ANTIBODIES
Binds to B and T cells Lymphomas Binds to vascular endothelial growth factor Binds to CD33 on leukemic cells Binds to CD20 on lymphoid cells Colon cancer Renal cancer Acute myelocytic leukemia Lymphomas Lymphomas
Immunosuppression Hypersensitivity Bleeding Hypertension Myelosuppression Delivers radiation to cancer cells Myelosuppression Fever Rash Hypersensitivity Immunosuppression Hypersensitivity Cardiac toxicity Local extravasation causing tissue necrosis Myelosuppression, with leukopenia and thrombocytopenia 4 to 6 wk after treatment Alopecia Lethargy Fever Hemolytic-uremic syndrome
Gemtuzumab Ibritumomab tiuxetan
Binds to CD20 on Iodine-131 lymphoid cells tositumomab Tositumomab Rituximab Trastuzumab Binds to CD20 on B cells Binds to HER2/neu receptor
B-cell lymphoma Breast cancer
OTHER ANTIBIOTICS Mitomycin Inhibits DNA synthe- Breast cancer sis by acting as Colon cancer a bifunctional Gastric adenocarcinoma alkylator Lung cancer Transitional cell cancer of the bladder
THE
SECTION SUBJECT TOPIC
Hematology and Oncology Principles of Cancer Therapy Modalities of Cancer Therapy
MERCK MANUALS
FOR HEALTHCARE ONLINE MEDICAL LIBRARY PROFESSIONALS
COMMONLY USED ANTINEOPLASTIC DRUGS—Continued
DRUG MECHANISM OF ACTION COMMONLY RESPONSIVE TUMORS TOXICITY AND COMMENTS
PLATINUM COMPLEXES Carboplatin Establishes cross links Breast cancer within and between Lung cancer DNA strands Ovarian cancer Cisplatin Same as for carboplatin Bladder cancer Breast cancer Head and neck cancer Gastric cancer Lung cancer (especially small cell) Testicular cancer Colon cancer
SPIDLE POISON (FROM PLANTS): TAXANES Docetaxel Promotes assembly of Breast cancer microtubules Head and neck cancer Lung cancer Ovarian cancer Paclitaxel Same as for docetaxel Bladder cancer Breast cancer Head and neck cancer Lung cancer Ovarian cancer
SPIDLE POISON (FROM PLANTS): VINCAS Breast cancer Vinblastine Arrests mitosis by inhibiting polymer- Ewing’s sarcoma ization of microLeukemia tubules Lymphomas Testicular cancer Vincristine Same as for vinblastine Acute leukemia Lymphoma
Hematology and Oncology Principles of Cancer Therapy Modalities of Cancer Therapy
MERCK MANUALS
FOR HEALTHCARE ONLINE MEDICAL LIBRARY PROFESSIONALS
COMMONLY USED ANTINEOPLASTIC DRUGS—Continued
DRUG MECHANISM OF ACTION COMMONLY RESPONSIVE TUMORS TOXICITY AND COMMENTS
TOPOISOMERASE INHIBITORS: ANTHRACYCLINES Daunorubicin Inhibits topoisomerase Leukemia (daunoII and causes DNA mycin) strands to break Doxorubicin Same as for daunorubicin Acute leukemia Breast cancer Lung cancer Lymphoma
Myelosuppression Cardiac toxicity at cumulative dosage > 1000 mg/m2 Nausea Vomiting Alopecia Myelosuppression Cardiac toxicity at cumulative dosage > 550 mg/m2 Myelosuppression Cardiac toxicity at cumulative dosage > 1000 mg/m2
Epirubicin
Same as for daunorubicin
Acute myelocytic leukemia Breast cancer Gastric cancer
TOPOISOMERASE INHIBITORS: CAMPTOTHECINS Irinotecan Inhibits Colon cancer topoisomerase I Lung cancer Rectal cancer Topotecan Same as for irinotecan Ovarian cancer Small cell lung cancer
TOPOISOMERASE INHIBITORS: PODOPHYLLOTOXINS Inhibit topoisomerase Acute leukemia Etoposide II and cause DNA Hodgkin lymphoma Teniposide strands to break Lymphoma Lung cancer (especially small cell) Testicular cancer
Nausea Vomiting Myelosuppression Peripheral neuropathy Increased toxicity in renal failure Neutropenia Cleared by liver and kidneys Neutropenia Nausea Vomiting Acne Diarrhea Leukopenia Hepatocellular toxicity Edema
Hepatocellular cancer Inhibits intracellular and cell surface Renal cancer kinases (eg, vascular endothelial growth factor receptors) Inhibits receptor tyrosine kinases GI stromal tumors Renal cancer