DRUG MOA USES ADVERSE EFFECTS PENETRATE ROUTE / RESISTANCE

CNS ELIMINATION
Cyclophosphamide Alkylates DNA at N7 CLL (CHOP-R) Myelosuppression YES (low Oral/Renal Low CYP2B
position of guanine level)
residues (covalent) Non-Hodgkins High Risk N/V

Interstrand crosslinks kill Breast CA (CMF) Severe alopecia

tumor cell, intrastrand
cause secondary cancer Lung CA (CAV, CAE) Hemorrhagic cystitis
(treat with Mesna which
Activated by CYP2B Immunosupressant inactivates acrolein)
Carmustine Crosslinks guanine and CNS Tumors Delayed YES Parenteral, AGT can remove
cytosine (CG) myelosuppression Wafer/Renal carmustine after
Lymphomas it bonds with
Delayed Pulmonary guanine
toxicity
Patients with
CNS Effects (seizures) increased AGT
have more
High Risk N/V resistance
Cisplatin Crosslinks adjacent Testicular CA Renal toxicity NO Parenteral/ Increased efflux
Oxaplatin guanines & adenine and (less with carboplatin) Renal (ATP7B)
cytosine (GG/AG) Colon CA (FOLFOX)
(Oxaplatin better) High Risk N/V Decreased influx
Intrastrand – bends DNA, (copper
inhibits DNA synthesis, Ovarian CA Peripheral Neuropathy transporter)
prevents repair
Melanoma Ototoxicity Inactivated by
glutathione
Darcarbazine Activated by liver Dar High risk N/V (dar) Dar – NO Dar –
Procarbazine enzymes Hodgkins Parenteral
Melanoma Alopecia Pro – YES
Crosslinks DNA Myelosuppression Pro – Oral
Pro
Inhibits RNA and protein Brain tumors Leukemogenic,
synthesis Hodgkins teratatogenic (pro)
DRUG MOA USES ADVERSE EFFECTS PENETRATE ROUTE / RESISTANCE
CNS ELIMINATION
Busulfan Crosslinks DNA CML Myelosuppression YES Oral
(thrombocytopenia) Parenteral/
Greater activity against Renal
myeloid cells than Pulmonary fibrosis (no
lymphoid treatment)

Alopecia (permanent)
Methotrexate Mimics folic acid Breast CA (CMF) Bone marrow NO Oral Decreased influx
suppression Parenteral/ (folate receptor,
Inhibits DHFR Choriocarcinoma Renal folate
GI toxicity transporter)
Polyglutamated form is ALL
more active Stomatitis Increased DHFR
RA expression
Inhibits thymidylate Kidney damage
synthase (TS) Psoriasis
Hepatotoxicity (long
Leucovorin rescue term use)
Purine antagonist Mimics DNA precursors 6-MP Myelosuppression NO Oral/Renal Low HPRT levels
6-MP ALL (needed for
6-TG Converted to thio-dGTP Hepatotoxicity (6-TG) Reduced by activation)
6-TG food
Inhibit DNA polymerase, AML Immunosuppression High TPMT
chain termination CML (inactivates)
TPMT inactivates (low
MeTIMP (6-MP) inhibits IBD, levels lead to increased
de novo purine Immunosuppressor toxicity)
biosynthesis
Allopurinol prevents
Activated by HGPRTase inactivation of 6-MP
but NOT 6-TG
DRUG MOA USES ADVERSE EFFECTS PENETRATE ROUTE / RESISTANCE
CNS ELIMINATION
5-FU Analogue of uracil Colorectal CA Myelosuppression YES Parenteral Increased TS
(utilized more rapidly by (FOLFOX) Topical/ expression
tumor cells) Oral/GI ulceration Biliary
Breast CA (CMF) TS has negative
5-FdUMP binds TS Neurotoxicity feedback
Actinic keratosis inhibition on its
5-FdUTP incorporates and basal cell Inflammation, irritation own synthesis,
into DNA (repair carcinoma (topical) – lets you know
attempts cause damage) drug is working Increased DPD
Leucovorin (DPD
5-FUTP inhibits RNA increases efficacy inactivates)
synthesis
Gemcitabine (dFdC) Ribonucleotide Pancreatic CA Myelosuppression ? Parenteral/ Increased
reductase inhibitor Renal cytidine
Alopecia deaminase

Decreased influx
Doxorubicin DNA intercalation Dauno Cardiotoxicity (CHF) NO Parenteral/ Increased efflux
Adriamycin AML Irreversible from free Biliary (MDR-1)
Hydroxydanorubicin Inhibits topo II – ALL radical damage
Religation inhibited Idarubicin (less Some urine Inactivation by
Doxo cardiotoxicity) (red urine) glutathione
Cleaves both strands Breast CA
Non-Hodgkins Tissue damage
Reactive oxygen species Hodgkins (blistering), hand-foot
Lung CA syndrome, mucosal
Unwinds DNA, inhibits ulcers
DNA & RNA synthesis
Myelosuppression

Liposomal formulations
DRUG MOA USES ADVERSE EFFECTS PENETRATE ROUTE / RESISTANCE
CNS ELIMINATION
Bleomycin Not well understood Hodgkins Pulmonary toxicity ? Parenteral/ DNA damage
lymphoma (ABVD) (inactivated by amino Renal repaired by
Free radical through hydrolase, low APE1
Fe2+ and Cu2+ concentration in skin
and lungs) Increased APE1
Single and double
stranded breaks
Camptothecin Inhibits topo I – Topo Topo Topo YES Parenteral/ Increased efflux
Irinotecan Religation inhibited Ovarian CA Neutropenia (ABC
Toptecan Irino Topo – Renal transporters)
Cleaves a single strand of Irino Irino Unknown
DNA Colorectal CA Neutropenia Irino – Biliary Irino inactivated
Severe Diarrhea by CYP3A
Alopecia
Etoposide Inhibits topo II – cleaves Lung CA (CAE) Myelosuppression NO Parenteral/ Increased efflux
Teniposide both DNA strands Renal (MDR1)
Mild alopecia
Religation inhibited Topo II
mutations
Collision with replication
machinery required
Vincristine Binds to tubulin dimer Vincristine Vincristine NO Parenteral/ Increased efflux
Vinblastine and blocks assembly of Non-Hodgkin Peripheral neuropathy Biliary (MDR1)
microtubule Lung CA Hyperuricemia
FATAL IF Microtubule
M phase arrest Vinblastine Vinblastine GIVEN mutations
Hodgkins (ABVD) Myelosuppression INTRATHECAL
Paclitaxel Binds to B-tubulin Breast CA Myelosuppression NO Parenteral/ Increased efflux
Docetaxel Biliary (MDR1)
Inhibits microtubule Kaposi’s Sarcoma Peripheral neuropathy
disassembly Tubulin
Hypersensitivity mutations
Apoptosis
Alopecia
DRUG MOA USES ADVERSE EFFECTS PENETRATE ROUTE / RESISTANCE
CNS ELIMINATION
Cetuximab Binds extracellular Colon CA Acneiform rash (90%) Constitutive
domain of EGFR (+Irinotecan) activation of
Hypersensitivity downstream
Occludes ligand binding Squamous cell CA infusion reaction kinases
site, blocks receptor
dimerization Diarrhea

Illicits host immune

response and receptor is
internalized and
degraded

Trastuzumab EGFR (HER-2) Metastatic breast Hypersensitivity

CA reactions
Blocks HER-2 mediated
cell growth Diarrhea

Overexpressed in breast Cardiotoxicity

CA

Bevacizumab VEGF (Vascular Metastatic colon Fatigue Evasive

Endothelial Growth CA resistance
Factor) present on blood Diarrhea (alternative
vessel surface Non-small cell lung pathways
CA GI Bleeding develop to
Antibody binds and sustain tumor
prevents it from binding Metastatic breast growth)
to receptor CA
Intrinsic (pre-
Prevents angiogenesis existing non
needed to nourish responsiveness)
growing tumor
DRUG MOA USES ADVERSE EFFECTS PENETRATE ROUTE / RESISTANCE
CNS ELIMINATION
Rituximab CD20 antigen Non-hodgkins Hypersensitivity
infusion reaction
Exact MOA unknown CLL

RA (+MTX)
Gemtuzumab Conjugated with a CD33 positive AML Hypersensitivity
cytotoxic antibiotic called infusion reaction
calicheamicin
Myelosuppression
CD33 on surface of 90%
AML cells but not on Hepatocellular damage
normal marrow stem
cells

Taken up into cells and

sequestered into
lysozymes where
calicheamicin is released

Leads to double stranded

breaks and cell death

Imatinib (Gleevec) Inhibits activity of unique CML N/V Oral/Biliary Bcr-abl

kinase in CML cells amplification or
(Bcr-abl kinase) GI tumors Diarrhea Inactivation mutation
containing c-kit P450’s
Philadelphia mutation
chromosome

Erlotinib EGFR tyrosine kinase Non-small cell lung Rash Oral/Biliary

Gefitinib CA
Inhibits N/V CYP3A4
autophosphorylation Pancreatic CA active,
Diarrhea inactive
DRUG MOA USES ADVERSE EFFECTS PENETRATE ROUTE / RESISTANCE
CNS ELIMINATION
Tamoxifen Inhibits estrogen binding Breast CA Well tolerated Oral/Biliary
to the Estrogen Receptor Early stage
(ER Metastatic Hot flashes P450

ER partial agonist Increased risk of

endometrial CA
Estrogen promotes
growth of breast and Increased risk of
endometrial CA thromboembolitic
events
Anastrozole Inhibit estradiol Postmenopausal, Well tolerated, hot Oral/
synthesis ER+ breast CA flashes, fatigue
(Aromatase 10% Renal
Inhibitor) Tamoxifen resistant Weight gain
90% Unclear
Osteoporosis
Flutamide Binds to androgen Prostate CA Hot flashes Oral/Renal
receptor (AR) and
(Antiandrogen) inhibits effects of Gynecomastia
androgen
Potential increase in
Blocks synthesis of breast CA incidence
androgen targeted genes
Leuprolide Synthetic analogue of Prostate CA Hot flashes Oral/Renal
Gonadotropin-releasing
hormone (GnRH) Uterine fibroids Impotence
Stimulates release of FSH
and LH which stimulate Endometriosis Gynecomastia
release of testosterone
and estradiol
Low conc. stimulate
testosterone and
estradiol (high conc.
Inhibit release)
DRUG MOA USES ADVERSE EFFECTS PENETRATE ROUTE / RESISTANCE
CNS ELIMINATION
Cyclosporine Inhibits calcineurin Organ transplant Nephrotoxicity Parenteral,
activity Oral, Topical/
Graft vs. host Diabetogenic Hepatic
Prevents IL-2 synthesis, CYP3A4
blocks T-cell proliferation Dry Eye
Autoimmune disease

Sirolimus Binds FKBP12, inhibits Transplantation Myelosuppression Oral/P450

(Macrolide) mTOR
Graft vs. host Hyperlipidemia
Inhibits cell cycle
progression

Inhibits T and B-cell

proliferation

Mycophenolate Hydrolyzed to active Transplantation GI Irritation Oral,

mofetil drug in liver Parenteral/
Graft vs. host D/V Renal
Non-competitive
inhibitor of IMPDH Drug-drug interactions Decreased by
Tacrolimus decreases antacids
Used in de novo purine elimination by
synthesis (B and T-cell blocking conversion of
synthesis) MPA to MPAG

Azathioprine Coverted to 6-MP Transplantation Bone Marrow Oral,

suppression Parenteral/
Inhibits DNA synthesis in RA Renal
T-cells GI disturbances

Allergic reactions
DRUG MOA USES ADVERSE EFFECTS PENETRATE ROUTE / RESISTANCE
CNS ELIMINATION
Prednisone Inhibits production of Non-hodgkins Long term use: Oral/Renal
inflammatory mediators
like PG’s, LT’s, histamine Transplantation Muscle wasting

Inhibits proliferation of Graft vs. host Cushing’s syndrome

lymphoid cells
Autoimmune Inhibits osteoblast
Inhibits IL-1 production disease production

Aldesleukin Recombinant IL-2 Renal cell CA High dose: Parenteral/

(cytokine) Renal
Activates and induces Metastatic Hematological
proliferation of T-cells melanoma deficiencies

Activate the immune Fluid retention

system to attack the
tumor Renal dysfunction

Interferon alpha Increases activity of Melanoma Leukopenia Parenteral/

(cytokine) immune cells Renal
Kaposi’s sarcoma Flulike illness

Erythropoietin Binds to erythropoietin Anemia of chronic Hypertension Parenteral

receptors on RBC disease
progenitors Thrombotic
CA complications
Induces release of RBC’s
from bone marrow HIV Allergic reactions

Filgrastim G-CSF stimulator Bone marrow Better tolerated than

deficiency following GM-CSF
Increases proliferation of chemotherapy and
neutrophils bone marrow Mild/moderate bone
transplant pain
 DRUG MOA USES ADVERSE EFFECTS PENETRATE ROUTE / RESISTANCE
CNS ELIMINATION
Sargramostim GM-CSF stimulator Bone marrow Fever
deficiency following
Increases proliferation of chemotherapy and Myalgia
granulocytes, bone marrow
monocytes/macrophages transplant Malaise

Capillary leak syndrome

Gardasil L1 capsid protein Prevention of Fever 3 IM shots
cervical CA and 0,2,6 months
NOT an attenuated virus genital warts Pain at injection site
(strains 6,11,16,18)
Hypersensitivity
reaction

Lung Cancer Breast Cancer Colon Cancer Hodgkin’s Lymphoma Non-Hodgkin’s Lymphoma,
CLL
CAV CMF FOLFOX ABVD
CHOP-R
C – cyclophosphamide C – cyclophosphamide Fol – folinic acid (Leucovorin) A – adriamycin
A – adriamycin M – methotrexate F – 5-FU B – bleomycin C – cyclophosphamide
V – vincristine F – 5-FU OX – oxaplatin V – vinblastine H – hydroxydaunorubicin
D – darcarbazine O – oncovin
CAE P – prednisone
R – rituximab
C – cyclophosphamide
A – adriamycin
E – etoposide

Biliary (“TIPDFIVE”)
T – tamoxifen
I – imatinib
P – paclitaxel
D – doxyrubicin (adriamycin)
F – 5-FU
I – Irinothecan
V – vinblastine/vincristine
E - erlotinib