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(1) CYTOTOXIC DRUGS
DRUG MOA CLINICAL USE TOXICITY ANTIDOTE
ALKYLATING AGENTS
Mechlorethamine
Bifunctional alkylation “Nitrogen Mustard” MOPP regimen for
HODGKIN’S LYMPHOMA
Tissue necrosis
Cyclophosphamide
“Phosphoramide Mustard” Hemorrhagic cystitis
Ifosfamide
Monofunctional alkylation Sarcomas Hemorrhagic cystitis Mesna
Melphalan Prior to Bone Marrow transplantation
Chlorambucil Chronic B-cell lymphocytic leukemia and lymphoma
Immunosuppressive therapy (SLE/ Rheumatoid therapy)
Busulfan Prior to Bone Marrow transplantation
Venoocclusive disease of the liver
Nitrosoureas
Penetrates the CSF “Carmustine” / BCNU
Gliomas; Brain tumors Multiple myeloma Bone marrow transplant
Phenobarbital
Dacarbazine Generates active metabolite: MTIC (Monomethyl triazenoimidazole carboxamide)
ABVD regimen for HODGKIN’S LYMPHOMA
Flu-like syndrome of fever malaise, myalgias
Acetaminophen predication
Temozolomide
Dacarbazine analog Gliomas Radiation therapy
ANTIMETABOLITES
(1) FOLIC ACID ANALOGS
Methotrexate
Permetrexed
Inhibits DHFR enzyme (DIHYDROFOLATE REDUCTASE)
S-phase specific
Unable to polyglutamate methotrexate Multifolate antagonist Inhibits tumor enzymes
Intrathecal prophylaxis in
lymphomas & leukemias Choriocarcinoma
NON-HODGKIN’S
LYMPHOMA Osteosarcoma Leukemia Urine alkalinization
1
st line metastatic
mesethelioma 2
nd line metastatic non-
small cell lung cancer
Accumulation in 3rd
spaces (Ascites, Pleural effusion) Bone marrow suppression
Leucovorin Vitamin B and Folic acid
(2) PYRIMIDINE ANALOGS
5-FU
Capecitabine (prodrug of 5-FU)
Cytarabine
Inhibits Thymidilate Synthase Inactivated by Dihydropyrimidine Dehydrogenase enzyme in the liver Converted by Thymidine Phosphorylase to 5-FU Analog of 2-deoxycytidine Converted by Deoxycytidine kinase to an active for of 5-
Colorectal cancer Breast cancer
----
Induction of remission to
ALL
Hand-foot syndrome Myelosuppression GI disturbances Conjunctivitis
Leucovorin
Gemcitabine monophosphate nucleotide
----
Only drug effective for
pancreatic cancer Mild therapy; no alopecia
Myelosuppresion
(3) PURINE ANALOGS – inhibits HGPRT enzymes
Mercaptopurine Guanine analog Induction of remission to ALL Myelosuppression
Thioguanine
Guanine analog Induction of remission to AML
Myelosuppression
Fludarabine Adenosine analog Chronic lymphocytic leukemia
CD4 T-cells depletion
Cladribine Adenosine analog Hairy cell leukemia
CD4-Tcells depletion
ANTIMITOTIC
(1) VINCA ALKALOIDS –
Vincristine
M-phase specific; Binds to tubulin causing microtubule dissollution
NON-HODGKIN’S
LYMPHOMA together with CHOP (Cyclo, Prednisone, Doxorubicin)
HODKIN’S LYMPHOMA together with MOPP (Meclorethamine, Prednisone, Procarbazine)
Neurotoxicity, numbness, tingling, loss of DTR
Vinblastine
HODGKIN’S LYMPHOMA together with ABVD (Doxorubicin, dacarbazine, bleomycin)
Myelosuppression
Vinorelbine
Adjuvant and metastatic NSCLCA Myelosuppression
(2) TAXANE
Paclitaxel
Promotes, rather than inhibits microtubule formation Prevents microtubule destabilization
Breast cancer Lung cancer Ovarian cancer
Neutropenia Neuropathy
Cromophore vehicle
Docetaxel
More pronounced neutropenia than paclitaxel Metabolized in the liver by CYT p450
(3) EPOTHILONES
Ixabepilone Similar to taxanesbut MORE POTENT!
Metastatic Breast cancer
Metabolized in the liver by CYT p450
TOPOISOMERASE- INTERACTIVE AGENTS
(1) CAMPHOTERICIN
Irinotecan Major excretion pathway is GLUCORONIDATION by UGT1A1
s Patients with CRIGGLER NAJAR/ GILBERT’S SYNDROME are more affected Delayed & Acute diarrhea
TOPOTECAN
Metastatic ovarian cancer
Neutropenia
(2) EPIPODOPHYLLOTOXINS
Etoposide Conditions lowering albumin levels will lead to increased free fraction, increasing toxicities
Acute non-lymphocytic leukemia
TUMOR ANTIBIOTICS
(1) ANTHRACYCLINES
Doxorubicin Binds with Topoisomerase-II Generates free radicals Intercalates DNA Promotes apoptosis
Tumor antibiotic from
streptococcus spp.
Lymphomas, Leukemia, Breast cancer, Sarcoma, SCLCA
Cardiotoxicity due to free radicals generated
Daunorubicin ALL and AML
Epirubicin Breast Cancer Less cardiotoxic
Mitoxantrone Acute non-lymphocytic leukemia, hormone-resistant prostate cancer
Liposomal doxorubicin Ovarian cancer Lymphomas
Less cardiotoxic, less neutropenia
(2) BLEOMYCIN Oxidative DNA damage Pulmonary fibrosis
Decline in CO2 diffusion capacity
Cutaneous toxicity
(3) MITOMYCIN ANAL CANCER! HUS
PLATINUM COMPOUNDS – forms DNA ‘ADDUCTS’ which are recognized by MMR, that will promote apoptosis
Cisplatin Germ cell tumor Lung cancer Head and neck cancer Ovarian cancer
Nephrotoxicity Most emetogenic
Renal toxicity Ototoxicity Myelosuppression
Carboplatin Ovarian cancer Lung cancer
Less reactive than cisplatin, better tolerated
Oxaliplatin GI cancer, Ovarian cancer Germ cell cancer Cervical cancer Pancreatic cancer
Less neutropenia Less nephrotoxic, more neuropathic
L-asparaginase ALL Hypersenistivity reactions Mimimal Bone marrow and GI toxicity Hyperglycemia, Hypoalbuminemia, protein C and S deficiency
Mitotane Adrenocortical carcinoma
(2) HORMONAL TREATMENT DRUG MOA CLINICAL USE TOXICITY
Adrenocorticosteroids Promote apoptosis Immunosuppresion Glucose intolerance Osteoporosis Water retention GI ulcers
Aromatase Inhibitors Prevent formation of estrogen from adrenal gland and adipose tissue by inhibiting AROMATASE
Bone mineral density, bone pains, increased fracture rates Musculoskeletal problems!
For post-menopausal ER/PR+ breast cancer patients in adjuvant, neoadjuvant, metastatic setting
Anti-Estrogen Blocks estrogen receptors itself Thrombosis risk Endometrial CA Hot flashes, nausea, vomiting, menstrual irregularities
GnRH analogs Stimulates FSH and LH production by the pituitary gland then will late cause negative feedback inhibition
Breast cancer Prostate cancer
Initial flare reaction
Anti-androgen Binds to androgen receptors and causes complete androgen blockade
Prostate cancer Decreased libido Hot flashes Gynecomastia Mastodynia Paradoxical stimulation of androgen receptors
BIOLOGICAL RESPONSE MODIFIERS
DRUG CLINICAL USE SIDE EFFECT ANTIDOTE
Interleukin-2 Expands T-cell response that is cytolytic for tumor cells Melanoma Renal cell carcinoma AML
Hypotension Peripheral edema Azotemia
G-CSF Filgrastim/ Lenograstim Expands population of neutrophil precursors Prophylaxis for chemotherapy induced neutropenia
Fever Chills
TARGETED RESPONSE
DRUG CLINICAL USE SIDE EFFECT ANTIDOTE
MONOCLONAL ANTIBODIES
Traztuzimab Her2 receptor Breast cancer CHF Hypersensitivity
Bevacizumab Vegf receptor Angiogenesis Hypertension, bleeding, proteinuria Hypersensitivity reactions
Cetuximab EGFR receptor Colorectal cancer Head and neck cancer
Skin rashes Hypersensitivity reactions
Panitumomab EGFR receptor Colorectal cancer Hypersensitivity reactions
Rituximab CD20 receptor B-cell lymphomas Hypersensitivity reactions
TYROSINE KINASE INHIBITORS
Imatinib (Gleevec) Bcr-Abl TKO in CML CD 117 TKl in GIST
Rashes Asthenia Weakness
Gefitinib EGFR TKl in NSCLCA
Erlotinib EGFR TKl in NSCLCA
Sunitinib Multikinase Renal and liver cancer
Sorafenib Multikinase Renal and liver cancer
Lapatinib EGFR and HER2 TKl Breast Head and neck cancer
PROTEOSOME INHIBITOR
Bortezomib Degrades proteosomes that denatures IKb
MTOR INHIBITOR
Everolimus Pancreatic neuroendocrine tumors Advanced renal cell cancer
Temsirolimus Advanced renal cell cancer
Intrathecal Administration Methotrexate Cytotoxic agent (Antimetabolite)
Cytarabine Cytotoxic agent (Antimetabolite)
Can cross Blood Brain Barrier Nitrosoureas Cytotoxic agent (Alkylating agent)
Temoxolomide Cytotoxic agent (Alkylating agent)
Teniposide Topoisomerase interactive agent
Hydroxyurea