Oncology

A Pharmacology Study Guide

Kurt Degenhardt, Ph.D.

Arthur Prancan, Ph.D., Course Director

Pharmacology
Touro College of Osteopathic
Medicine
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 FACULTY

Arthur Prancan, Ph.D., Course Director

329 Touro College Building (646) 981-4612
Arthur.Prancan@touro.edu

Kamilah Ali, Ph.D., Assistant Professor

442 Touro College Building (646) 981-4614
Kamilah.Ali6@touro.edu

Kurt Degenhardt, Ph.D., Assistant Professor

512 Touro College Building (646) 981-4608
Kurt.Degenhardt@touro.edu

Clifford Knapp, Ph.D., Associate Professor

60 Prospect Avenue, 845-648-1000, ext. 60257
Clifford.Knapp@touro.edu

Tanchun Wang, Ph.D., Assistant Professor

60 Prospect Avenue, 845-648-1000, ext. 60228
Tanchun.wang4@Touro.edu

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 STUDY GUIDE CONTENTS
Essential Objectives for Focused Learning p. 1
Intro. To Cancer Chemotherapy p. 2
Alkylating Agents p. 4
Antimetabolites p. 7
Hormonal Cancer Management p. 9
Antibiotics and Vinca Alkaloids p. 11
Monoclonal Antibodies p. 14
Anticancer Drugs for Molecular Targets p. 16
Learning Objectives p. 18

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 Essential Objectives for Focused Learning
Drug Classification

Drug Mechanism of Action

Mechanism of Usefulness

Mechanism of Toxicity
Drug Classification
All drugs belong to a GROUP

Identify a group according to chemical characteristics, mechanism of action or

clinical application

Learn the drug classes and individual drugs in the group

Then, a subsequent review can have an end point, establishing confidence.

Mechanism of Action
Each drug involves itself in the biology of the patient or infective agents

Identify EXACTLY what the drug does

This may not be the mechanism of usefulness, but it can start the ball rolling in the
right direction

EVERYONE WILL DETERMINE WHETHER OR NOT YOU KNOW THIS!

Mechanism of Usefulness
This will differ with the disease

For each application, how does the mechanism of action become useful?

This is also known as THERAPY

Mechanism of Toxicity

All drugs can cause trouble

Many side effects are simply TOO MUCH THERAPY

Additional side effects must be learned

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Touro College of Osteopathic Medicine
Pharmacology 2
Oncology
Learning Objectives

Introduction to Cancer Chemotherapy

1. Describe Log-Kill and Drug Combination for Cancer Chemotherapy

Identify drugs which can be used to recover from anemia and thrombocytopenia
2. Describe the roles of G-CSF, Filgrastim and Pegfilgrastim in patient response to
chemotherapy
3. Palifermin use
4. Dexrazoxane use
5. Usefulness of Rasburicase and Allopurinol
6. Usefulness of Ondansetron, Metoclopramide and Promethizine

Alkylating Agents

1. Know the mechanism of drug action and tumor cell resistance, clinical use,
pharmacokinetics & general adverse effects of alkylating agents and Platinol drugs.
2. Know drug class (cell cycle specific vs. cell cycle non-specific)
3. Know clinically significant drug interactions (if any)
4. Know adverse effects that are unique to a specific drug in
the class of alkylating agents. (For eg. drug induced nephrotoxicity)

Antimetabolites
1. Know the mechanism of drug action and tumor cell resistance, clinical use, &
adverse effects of anti-metabolite chemotherapeutic drugs
2. Know Absorption, Distribution, Metabolism & Elimination (ADME) of
chemotherapeutic agents
3. Know drug class (cell cycle specific vs. cell cycle non-specific)
4. Know drug interactions (if any)
5. Know adverse effects that are unique to a specific drug

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Hormonal Cancer Management

1. Define SERM; know which drugs are SERMs

2. Define SERD; know which drugs are SERDs
3. Know where aromatase works and the outcome of blocking its action
4. Which drugs are indicated for use in Estrogen Receptor (ER) positive breast
cancer?
5. Know the advantages of Raloxifene and Fulvestrant over Tamoxifen
6. Which drugs are aromatase inhibitors and what is their advantage over tamoxifen?
7. What is the MOA and toxicity for diethylstilbesterol?
8. Flutamide MOA and Toxicity
9. Define the need for flutamide in early treatment by leuprolide or goserelin

Anticancer Antibiotics, Vinca Alkaloids and Natural Products

1. Define the MOA and toxicity for doxorubicin

2. Define the MOA and toxicity for bleomycin
3. Define the MOA for actinomycin-d and for mitomycin. Unusual toxicities?
4. Define MOA for the Vinca Alkaloids
5. Does vincristine have any special toxicities? Warnings?
6. How is the toxicity of vinblastine different from that of vincristine?
7. How is the toxicity of vinorelbine similar to that of vincristine?
8. Paclitaxel and docetaxel MOA, toxicity
9. Etoposide MOA
10. Topotecan MOA
11. L-Asparaginase MOA, cause of bleeding, cause of thrombosis?

Monoclonal Antibodies

1. MOA for Rituximab, Ibritumomab and Tositumomab

2. Identify clinical targets for the Rituximab group
3. Describe the advantages and disadvantages of Hot or Cold monoclonals
4. What is the MOA for the Ozagamicin portion of the Mylotarg combination?
5. How is safety built into this combination?
6. Identify the antigenic target and the major toxicity for each: alemtuzumab,
bevacizumab, cetuximab and trastuzumab

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Small Molecule Tyrosine Kinase Inhibitors

1. Which nib is the original antagonist at the BCR-ABL kinase? What is its MOA?
2. If mutation changes the active site for the primary drug, which nibs are ready to
stand in?
3. Which nib targets HER2 positive breast cancer?
4. Which two nibs are used for renal cell carcinoma, inhibit the VEGF TK, and change
skin color to yellow?
5. Which two nibs are used for non-small cell lung cancer, and demonstrate efficacy
via acne? What is their common MOA?

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 INTRODUCTION TO CANCER CHEMOTHERAPY
CONTROL OF ANEMIA, LEUCOPENIA, THROMBOCYTOPENIA
DRUG MOA USEFULNESS and
TOXICITY
Erythropoietin Stimulate RBC Recovery from low hemoglobin anemia during
Darbepoetin alfa formation bone marrow suppression
Granulocyte Colony Stimulates Stimulates neutrophil Bone pain
Stimulating Factor proliferation of phagocytic action. Prolongs
(G-CSF) neutrophil neutrophil survival. Splenic rupture is
Filgastrim precursors Reverses myelosuppression rare and serious
(Neupogen) during chemotherapy.
Peg Filgastrim Mobilizes peripheral blood
(Neulasta) stem cells collected for
autologous transplantation
Granulocyte- Stimulates Stimulates neutrophil Fever, malaise,
Macrophage Colony proliferation of phagocytic action. Prolongs arthralgia and
Stimulating Factor neutrophil neutrophil survival. myalgia. Capillary
(GM-CSF) precursors Reverses myelosuppression leak action.
during chemotherapy. Also Peripheral edema,
RBC and platelets. Not pleural effusions,
useful for collecting pericardial
peripheral blood stem cells. effusions. Possible
allergies
Oprelvekin (IL-11) Stimulate platelet Recovery from Poor response
formation thrombocytopenia and Cardiotoxicity
bleeding as platelet counts
drop
PROTECTION FROM TISSUE DAMAGE
Palifermin Recombinant Reduces the incidence and duration of severe
Keratinocyte oral mucositis; MOA-Stimulates the growth and
Growth Factor development of new epithelial cells to build up
(KGF). Binds to the mucosal barrier.
KGF receptor.
Dexrazoxane Derivate of 99% effective as antidote for needle
(Totect) EDTA ;Blocks extravasation damage during infusion of
Topoisomerase II Vinca Alkaloids
and Anthracyclines

Sodium thiosulfate for extravasation from nitrogen mustard 8

 Iron chelator Nitrogen Mustards
TUMOR LYSIS SYNDROME
Rasburicase Breaks down uric Hyperuricemia
acid to allantoin
Allopurinol Blocks xanthine Hyperuricemia
oxidase, stops
synthesis of Uric
Acid
ELECTROLYTE CONTROL
Sodium Polystyrene Sodium-potassium Hyperkalemia
Sulfonate ion exchange resin Free Potassium is decrease as it is exchanged for
(Kayexalate) sodium on this resin. Administered orally or
rectally.
Sodium Alkalinize urine Hyperphosphatemia
Bicarbonate and and increase urine Calcium phosphate can be eliminated with high
hydration volume volume, alkaline urine.
NAUSEA AND VOMITING
Ondansetron 5-HT3 receptor Nausea/Vomiting
antagonist Cisplatin N/V 75%. 10% with ondansetron.
Metoclopramide Blocks D2 and Nausea/Vomiting
5-HT3 receptors
Promethazine D2, M2 Blocker Nausea/Vomiting
Aprepitat (oral) Neurokinin-1 Used with 5-HT3 receptor antagonist and
Fosaprepitant (IV) (NK1) receptor glucocorticoid for delayed Nausea/Vomiting.
antagonist

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 ALKYLATING AGENTS
DRUG USEFULNESS TOXICITY
General MOA: Alkylation of DNA, RNA. Interfere with DNA replication. Cross-link
DNA N7 on Guanine between strands or along the same strand.
Cell Cycle Phase Non-Specific; Proliferation dependent
General Toxicity: Myelosuppression (N Neutropenia, Thrombocytopenia, anemia) which
is dose-related, cumulative over 7-10 days.
Gastrointestinal (Nausea, vomiting, stomatitis, diarrhea, anorexia)
Secondary malignancy.
NITROGEN MUSTARDS
Cyclophosphamide Lymphomas, leukemias, multiple Hemorrhagic cystitis. Always
myeloma, neuroblastoma, use good hydration. Use
retinoblastoma, and cancers of the MESNA( 2-mercaptoethane
breast and ovary. A pro-drug. sulfonate) to stop this toxicity at
Phosphoramide is the cytotoxic high cyclophosphamide dose.
metabolite, and Acrolein is toxic at Hematuria
urinary bladder
Ifosfamide Testicular, lung and breast cancer. Hemorrhagic cystitis. Always
Lymphomas. IV only. use MESNA( 2-mercaptoethane
sulfonate) with Ifosfamide to
stop this toxicity.
Mechlorethamine The original chemotherapeutic. Black Box Warning: Handling
Original use was as war gas caution, must adhere to
Mustard Gas, a vesicant that required protection of skin, eyes
attacks the eyes, lung. Indicated and mucous sites of clinical
for Hodgkins lymphoma, chronic team and patient from powder,
myelocytic leukemia and chronic solution and vapors.
lymphocytic leukemia. iv use Vessicant, extravasation causes
only. local necrotic damage. Use
Dexrazoxane immediately.
Melphalan Use for multiple myeloma, ovarian Black Box Warning: Severe
Chlorambucil cancer, malignant melanoma and Bone Marrow Suppression.
chronic lymphocytic leukemia. Leukemogenic.
Typical protocol: Dosed 6 mg/day
for 2-3 weeks. Stop for 4 weeks. Allergic reaction, pulmonary
Start 2mg maintenance when fibrosis.
platelets and white cells begin to
rise.

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 ALKYLATING AGENTS (cont.)
DRUG USEFULNESS TOXICITY
NITROSOUREAS
Carmustine Given iv. Also drug wafer under Bone marrow suppression is
(BCNU) skull via craniotomy. delayed 4-6 weeks after dosing.
N-N- High lipid solubility crosses BBB. Then takes 6 weeks to recover.
Bis(2Chloroethyl)- Used for brain cancers, multiple Delayed pulmonary fibrosis and
N-Nitrosourea myelomas, lymphomas. kidney failure, probably related
Cell cycle Non specific to cumulative dose.
Lomustine po only. Used for brain tumors. Slow onset of leucopenia, but
(CCNU) All nitrosoureas have good CNS watch WBC count.
N-(2chloroethyl)- penetration.
N-Cyclohexyl-N-
Nitrosourea
Streptozocin Pancreatic islet cell carcinoma Nephrotoxicity is dose limiting
THE PLATINUMS (Alkylating-Like, No Alkyl Groups)
These drugs have reactive chlorides which can be exchanged for N7 Guanine on DNA,
creating cross-linking in the same way as all agents above.
Cisplatin One of most often used cancer Nephrotoxicity is dose-limiting.
chemotherapeutic drugs. Often Add hydration and dieresis.
effective alone. Used in
combination to improve total Peripheral neurotoxicity. Nerve
anticancer efficacy and to conduction decreases.
reduce toxicity of individual
drugs. iv. T1/2 = 3 hr N/V is worst of most drugs. Can be
handled by ondansetron.
Used for carcinomas, sarcomas,
lymphomas and germ-cell Ototoxicity. Less
tumors. myelosuppression.
Carboplatin T1/2 = 30 hr. Ovarian No Nephrotoxicity. Much less N/V.
carcinoma, lung, head and neck Less Ototoxicity, less neurotoxicity.
cancer. Given iv. Myelosuppression to 10% of
control by 25 days afer dose.
Recovers.
Oxaliplatin Colorectal cancer Acute sensitivity to cold
temperature. Peripheral neurotox.

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 AKYLATING AGENTS (cont. #2)
DRUG USEFULNESS TOXICITY
Carboplatin Dosing according to kidney function.
CALVERT FORMULA FOR Carboplatin DOSING

Total Dose (mg)=(target AUC) (GFR + 25)

Normal AUC is 4-5 mg/ml.min. AUC of 6-7 doubles myelosuppression.
Nephrotoxicity is not the problem; myelosuppression can be severe in persistent dosing.
OTHER ALKYLATING AGENTS
Busulfan Chronic myelogenous leukemia Pulmonary fibrosis
(CML) (busulfan lung)
Procarbazine Hodgkin's disease and primary MAO Inhibitor. Can cause
brain tumors hypertension with
tyramine-rich foods.
Dacarbazine i.v., for malignant melanoma, Usual N/V
also for Hodgkins disease

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 ANTIMETABOLITES
DRUG MOA USEFULNESS TOXICITY
Methotrexate (MTX) Inhibits Complicated kinetics 1.Myelosuppression
(Folic Acid Analog) dihydrofolate Given orally (p.o.), treat with folinic
Cell cycle specific reductase (DHFR) to IV, IM, intrathecal. acid (Leucovorin)
at S phase block formation of rescue.
FH4 (tetrahydrofolic Filtered & secreted by 2. HIGH doses
acid) & cofactors. kidneys. dose in causes
1. Thymidine renal insufficiency nephrotoxicity with
(DNA) crystal
2. Purines nephropathy;
(DNA/RNA) Clinical Indications: Hydrate with IV
3. Proteins. Acute lymphoblastic bicarbonate to
lymphoma, breast & alkalinize urine &
choriocarcinoma. excretion.
Hepatoxicity,
mucositis
Pyrimidine analog 5 FU is a prodrug; Poor oral Bone marrow
Active metabolite bioavailability, I.V. depression
5-Flurouracil Only.
(5-FU) 1. 5-FUMP blocks Follows zero-order Oral and
Cell cycle specific RNA synthesis. kinetics at HIGH GI mucositis
at S phase 2. FdUMP blocks doses.
DNA synthesis; Folinic Acid
forms complex with (leucovorin)
FH4 cofactors & potentiates 5-FU.
thymidylate Clinical Indications:
synthetase to block Colorectal cancer;
de novo thymidine also breast, bladder,
synthesis. esophagus; basal cell
carcinoma.
Pyrimidine analog Requires Cytarabine is effective Myelosuppression
phosphorylation by for remission of acute pancytopenia
Cytarabine (cytosine nucleoside kinases to myelogenous
arabinoside; AraC) active form: leukemia, and
Cell cycle specific AraCTri-Phosphate management of non-
at S phase -inhibits DNA Hodgkins lymphoma
polymerase. and ALL.
Pyrimidine analog Phosphorylation by Metastatic pancreatic Myelosuppression
nucleoside kinases cancer
Gemcitabine produce di and tri-P Non-small cell lung Flu-like symptoms
gemcitabine. Inhibit cancer.
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 ribonucleotide
reductase. DNA
chain termination.
ANTIMETABOLITES (cont.)
DRUG MOA USEFULNESS TOXICITY
Purine Analog Prodrug converted 6- MP undergoes 1st Bone marrow
by HGPRT pass metabolism by suppression, N/V
6-Mercaptopurine converted to a faulty xanthine oxidase to
(6-MP) monophosphate 6-thiouric acid.
Drug Interaction:
Cell cycle specific nucleotide that Allopurinol blocks
at S phase blocks de novo metabolism of 6-
purine synthesis. Clinical Use:
MP Reduce dose
Faulty triphosphate of 6-MP by ~75% if
Childhood acute
nucleotide blocks given with
leukemia allopurinol.
(DNA & RNA
synthesis)

Purine Analog Inhibits DNA Non-Hodgkins Anemia,

polymerase lymphoma thrombocytopenia
Fludarabine Chronic lymphocytic and neutropenia
Phosphate leukemia.
Purine Analog Blocks adenosine Hairy cell leukemia Cough, fever, fatigue
deaminase T-cell lymphoma
Pentostatin

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 HORMONAL CANCER MANAGEMENT
DRUG MOA USEFULNESS TOXICITY
Selective Estrogen Blocks estrogen Typically is used in Hot flash,
Receptor Modulator receptor, antagonist to estrogen receptor thrombosis,
(SERM) estradiol. Some partial (ER) positive tumors. endometrial CA,
agonist action. May have benefit in sweating, N/V,
Tamoxifen May also decrease ER negative tumors. dizzy, edema,
TGF, increase TGF, vaginal bleed,
for a total decrease in cataract, stroke,
cell growth. uterine sarcoma.

Selective Estrogen Has Antiestrogenic Orally available, used vs Tamoxifen,

Receptor Modulator action on uterus and to treat or prevent no uterine cancer,
(SERM) breast, and estrogenic osteoporosis and ER no cataracts,
action on bone. positive breast cancer. less thrombosis, less
Raloxifene (Evista) stroke.
Hot flashes, leg
cramps.

Selective Estrogen Binds estrogen receptor, ER positive Breast N/V, hot flashes, GI
Receptor high affinity. Cancer symptoms.
Downregulator Competitive inhibitor of Given im once a
(SERD) etradiol. Changes month.
receptor to less viable Follows Tamoxifen
Fulvestrant form. Decreases when it is no longer
(Faslodex) receptor number. effective, or instead of
Tamoxifen.

Aromatase Aromatases convert First-line in N/V, hot flashes,

Inhibitors androstenedione and postmenopausal fatigue.
testosterone, into estrone women with ER
Anastrozole and estradiol. The drugs positive breast CA Risk of bone loss
Letrozole block the aromatases. who cannot tolerate and fracture.
(non-steroidal) tamoxifen. 5 years of
Exemestane No suppression of tamoxifen is followed Less thrombosis and
(steroid-irreversible glucocorticoids or by 2.5 years of endometrial CA
inhibitor) mineralocorticoid. aromatase inhib. than tamoxifen.

Megestrol Acetate Lower LH, Anti- Palliative treatment of May cause

(Megace) leutenizing effect at breast and hyperglycemia.
pituitary gland. endometrial cancer,
also prostate cancer.
Enhances appetite.

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 DRUG MOA USEFULNESS TOXICITY
Estrogen An orally available
synthetic nonsteroidal Prostate cancer Male breast cancer,
Diethylstilbestrol estrogen which No longer marketed cerebrovascular and
(DES) blocks endogenous in US. cardiovascular
androgen actions. thrombosis.
Luteinizing Bind to Luteinizing Used in treatment of Bone pain, hot
hormone releasing Hormone Releasing ER positive breast flashes, headache,
hormone receptor Hormone (LHRH) cancer. Goserelin stomach upset,
agonist (LHRH) receptor binds to LHRH depression.
Suppresses estrogen and receptors in the
Leuprolide androgen synthesis. pituitary cell.
Goserelin When these agents are Following an initial
used for men with LH surge, there is
(A prolonged half hormone-dependent internalization (or
life and 100 x the prostate cancer there is down-regulation) of
potency of the an initial surge of LHRH receptors and
natural releasing testosterone which can LH synthesis is
hormone) cause a tumor flare inhibited
before the feedback loop The reduction in LH
inhibits testosterone production achieves
synthesis. Therefore suppression of
flutamide is started estradiol to levels
along with these agents comparable to those
at the onset of therapy. observed in
postmenopausal
women.

Flutamide Competitive antagonist Leuprolide and Gynecomastia, GI

to testosterone and Goserelin may cause side effects.
dihydrotestosterone at an early loss of
androgen receptors. androgenic feedback
and a consequent
tumor flare early in
therapy. Flutamide is
added to suppress this
event.
Corticosteroids Cytotoxic Used in leukemia and Immunosuppressive
malignant lymphoma. GI ulceration,
Prednisone Prednisone is part of osteoporosis,
Prednisolone MOPP in Hodgkins psychosis, other
Hydrocortisone lymphoma and CHOP signs of chronic
Dexamethasone for Non-Hodgkins corticosteroid use-
Lymphomas.
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 ANTICANCER ANTIBIOTICS
*All are cycle-cell non-specific except bleomycin*
DRUG MOA USEFULNESS TOXICITY
ANTIBIOTICS
Doxorubicin 1. Inhibits Broad spectrum for solid, Myelosuppression
(Adriamycin) topoisomerase II soft tissue & (neutropenia), alopecia,
2. Intercalates DNA hematopoietic: mucositis, vesication.
3. Blocks DNA & Breast, endometrium,
RNA synthesis. ovary, testicular, thyroid, Cardiotoxicity is DOSE
4. Generates free stomach, bladder, LIMITING
radicals that liver & lung; Soft tissue (CUMULATIVE)
damage DNA. sarcomas, childhood Use dexrazoxone for
cancers e.g. Ewings cardiotoxicity
Pretty much block the whole cell cycle
sarcoma, & Dialated cardiomyopathy
rhabdosarcoma,
hematological cancers
acute lymphoblastic
leukemia, multiple
myeloma, Hodgkins &
non-Hodgkins lymphoma.
Daunorubicin See above. Acute myelogenous Cardiotoxicity like
(Cerubidine) leukemia doxorubicin.
Bleomycin Small peptide with Testicular cancer, Dose limiting toxicity
DNA & Iron Hodgkins lymphoma, occurs in lungs & skin.
binding regions on head and neck cancer. Lung damage and skin
opposite ends of the discoloration.
molecule; generates Pulmonary fibrosis
free radical that Alopecia
damages DNA. Raynauds syndrome

Blocks G2-Phase
Actinomycin-D Intercalates into Gestational Myelosuppression,
(dactinomycin) DNA- inhibits trophoblastic neoplasia, Alopecia, N/V,
replication Wilms tumor and Mucositis, Diarrhea,
rhabdomyosarcoma skin peeling and sun
sensitivity
Mitomycin Alkylating agent Gastric adenocarcinoma, Bone marrow toxicity,
interferes with DNA breast cancer, bladder lung fibrosis, renal
replication. tumors. damage.

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 ANTICANCER VINCA ALKALOIDS
DRUG MOA USEFULNESS TOXICITY
MICROTUBULE AGENTS: VINCA ALKALOIDS
Vincristine Binds -tubulin to block Non-Hodgkins CHOP. Peripheral
(Oncovin) polymerization with - Hodgkins Lymphoma neuropathy,
tubulin. MOPP, COPP, hyponatremia,
Dissolves & forms BEACOPP. Acute constipation and
crystals with lymphoblastic leukemia, hair loss.
microtubules. Arrest Wilms tumor.
tumor cells in M phase. Any spinal
M Phase inhibitors injection results in
100% mortality
Warnings

CautionThis preparation should be administered by individuals experienced in the

administration of Vincristine Sulfate Injection, USP. It is extremely important that the
intravenous needle or catheter be properly positioned before any Vincristine is injected. Leakage
into surrounding tissue during intravenous administration of Vincristine Sulfate Injection, USP
may cause considerable irritation. If extravasation occurs, the injection should be discontinued
immediately, and any remaining portion of the dose should then be introduced into another vein.
Local injection of hyaluronidase and the application of moderate heat to the area of leakage help
disperse the drug and are thought to minimize discomfort and the possibility of cellulitis.

FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY.

Vinblastine As above. Hodgkins lymphoma, Bone marrow
(Velban) Blasts the bone marrow non-small cell lung depression is dose-
cancer, Breast cancer, limiting. GI tox.,
head and neck, vesicant.
testicular.
Vinorelbine As above. Non-small cell lung Infection,
(Navelbine) cancer, Breast cancer. bleeding, anemia,
diarrhea,
peripheral
neuropathy,
asthenia.

Space intentionally left blank

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 ANTICANCER VINCA ALKALOIDS (cont.)
YEW ALKALOIDS
Paclitaxel Binds -tubulin to Breast, ovarian and non- Peripheral
(Taxol) stabilize microtubules & small cell cancers. neuropathy,
block mitosis. myelosuppresion
M blocker (delayed)

Docetaxel See above. Breast, ovarian and Neutropenia 95%

(Taxotere) cancers. Anemia 80%
Semi-synthetic Alopecia,
analog of Peripheral
paclitaxel Neuropathy, GI
Paclitaxel An intravenous Non-small cell lung Anemia,
protein-bound nanoparticle, albumin- cancer neutropenia,
(Abraxane) bound formulation of thrombocytopenia,
paclitaxel. It is designed alopecia,
to deliver a greater peripheral,
amount of neuropathy,
chemotherapy to cancer nausea, fatigue
cells with fewer side
effects. Use in
combination with
carboplatin

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 ANTICANCER NATURAL PRODUCTS
DRUG MOA USEFULNESS TOXICITY
EPIPODOPHYLLOTOXIN
Etoposide Forms ternary IV & P.O. Myelosuppression
(Vepesid) complex with Bioavailability is (primarily leukopenia),
Teniposide Topoisomerase II 50% . protein hypotension, mucositis,
(inhibits) causing binding. alopecia
irreparable DNA Clinical Uses:
strand breaks. Testicular cancer,
small cell lung
Blocks late S- to G2cancer, Kaposis
phase sarcoma
CAMPTOTHECINS
Topotecan Topoisomerase I Ovarian cancer, Diarrhea,
(Hycamtin) inhibitor. Forms Lung cancer, Myelosuppression,
covalent complex Cervical Cancer, Possible infection.
with DNA and Small cell lung cancer
Topoisomerase I.
prevents DNA
unwinding and
replication
S-phase specific
Irinotecan Topoisomerase I Colon cancer Severe diarrhea,
(Camtosar) inhibitor. Used w/ 5-FU and Severe
leucovorin immunosuppression
S-phase specific (Neutropenia)
OTHERS
L-Asparaginase Deamination Acute Lymphoblastic Hypersensitivity.
Pegaspargase enzymatic Leukemia (ALL) Coagulopathy and /or
deprivation of bleeding: Blocks
asparagine to the synthesis of clotting
leukemic cell. factors (bleeding) and
Antithrombin III,
Protein C (clotting).
Could cause stroke.
Hydroxyurea Blocks Chronic myelogenous Drowsiness, N/V,
ribonucleotide leukemia (CML), diarrhea, mucositis,
reductase-decrease melanoma bone marrow toxicity.

20
 DNA synthesis Adjunct potentiator of
chemotherapy.
S Phase specific

MONOCLONAL ANTIBODIES
DRUG MOA USEFULNESS TOXICITY
ANTIBODIES FOR CD20
Rituximab Binds CD20 on B-Cell B-Cell Lymphomas and Fatal infusion
(Rituxan) lymphomas, B-Cell Leukemias. reaction
chronic lymphocytic R-CHOP for Non-Hodgkins Cardiac arrest
leukemias and Lymphoma. Combination of Tumor lysis
melanoma stem cells. anticancer agents: Acute Renal Failure
Recruits immune C = Cyclophosphamide Infection
effector functions. H = Hydroxydaunorubicin Immunocompromise
O = Oncovin (Vincristine)
P = Prednisolone
Ibritumomab Rituximab radiolabeled Same indications. More expensive,
(Zevalin) with yttrium-90 Better efficacy more toxicity, more
Fewer doses handling (label)
Tositumomab Rituximab radiolabeled Same as above Same as above
(Bexxar) with I-131
ANTIBODY FOR CD30
Brentuximab CD30-directed antibody- Refractory Hodgkin neutropenia
vedotin drug conjugate (ADC) lymphoma and anaplastic peripheral sensory
(Adcetris) consisting of three large cell lymphoma neuropathy
components: 1) the fatigue
chimeric IgG1 antibody nausea
cAC10, specific for anemia
human CD30, 2) the upper respiratory
microtubule disrupting tract infection
agent, monomethyl diarrhea
auristatin E (MMAE), pyrexia
and 3) a protease- rash
cleavable linker that thrombocytopenia
covalently attaches cough
MMAE to cAC10 vomiting

21
 ANTIBODY FOR CD33
Gemtuzumab- CD33 antibody with a Acute Myelogenous Severe
Ozogamicin toxic (calicheamicin) Leukemia (AML) Myelosuppression.
(Mylotarg) antibiotic, which acts by Anemia
cell-directed cytotoxic, Neutropenia
DNA cross-linking and Thrombocytopenia
Topoisomerase II
inhibition.
MONOCLONAL ANTIBODIES (cont.)

ANTIBODY FOR CD52

Alemtuzumab Binds CD52 on mature Chronic Lymphocytic Severe infusion
(Campath) lymphocytes. Leukemia (CLL), T-Cell reaction is possible.
Lymphoma and Cutaneous
T-Cell Lymphoma
ANTIBODY FOR VEGF
Bevacizumab Directly binds VEGF Metastatic colorectal cancer, GI perforation
(Avastin) and inhibits its breast cancer, lung cancer. Wound dehiscence
stimulation of new blood Hypertension
vessels formation Nephrotic syndrome
(neovascularization) CHF, MI
Asthenia
Leukopenia
ANTIBODY FOR EGFR
Cetuximab Inhibits epidermal 75% of colorectal cancer Severe infusion
(Erbitux) growth factor receptor patients express EGFR. reaction. The
(EGFR) thus interfering Colon cancer, Head and neck infusion reaction
with cell growth. cancer. may be mediated by
histamine (H1), use
of diphenhydramine
(Benadryl) may
decrease the
symptoms.
Severe acne-like
rash. The rash is
reversible and is
considered a sign of
drug efficacy.
Diarrhea
22
 ANTIBODY FOR HER2
Trastuzumab Binds extracellular Major benefit for HER2 Cardiotoxicity. Must
(Herceptin) domain of the HER2, a positive breast cancer. monitor cardiac
tyrosine kinase receptor, function.
for cell differentiation
and growth, which is
expressed in breast
cancer.

Ipilimumab - CTLA4 blocker - block inhibition of CD8+ cells

Thalidomide - reduces levels of TNFalpha - decreases angiogenesis, proapoptotic

teratogen

Asparaginase - depletes asparagine, starves cell, treats T cell cancers

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 ANTICANCER DRUGS FOR MOLECULAR TARGETS
Small Molecule Tyrosine Kinase Inhibitors (TKI) > CYP3A4
THE NIBS
DRUG MOA USEFULNESS TOXICITY
Imatinib (Gleevec) Competes for the Blocks BCR-ABL kinase Myelosuppression
Also used for c-kit
ATP binding site (product of the Edema
on tyrosine kinase Philadelphia 9-22 N/V, myalgia, rash
of BCR-ABL- Chromosome) in Chronic Hepatotoxicity,
prevents Myelogenous Leukemia Chronic heart
phosphorylation (CML) failure
of tyrosine on
substrate
molecule.
Nilotinib (Tasigna) Same as above, Same as above Same as above, QT
Dasatinib (Sprycel) altered structure prolongation
to fit mutation of
Used when trastuzumab doesnt work
ATP binding site
Lapatinib (Tykerb) Inhibits EGFR Breast Cancer (HER2 +) Diarrhea
and HER2. Acts Fatigue
at the ATP site of Rash
Tyrosine Kinase
Sorafenib (Nexavar) Inhibits multiple Renal cell carcinoma Myelosuppression
tyrosine kinases: Hepatocellular carcinoma Hand-Foot
VEGFR/RAF syndrome,
kinases. diarrhea, High BP
Hair- skin color
Sunitib (Sutent) Inhibits multiple GI stromal tumor Myelosuppression
Sunitinib tyrosine kinases: Renal cell carcinoma Hand-Foot
Inhibits VEGFR, syndrome,
PDGFR, CSF-1R diarrhea, Same tox as bevacizumab
hepatotoxicity,
hypothydroidism
Gefitinib (Iressa) Inhibits EGFR Non-small cell lung Acne, GI
(HER1) ATP carcinoma Asthenia
Erlotenib (Tarceva) Inhibits tyrosine- Non-small cell lung Rash
kinase associated cancer, Diarrhea
epidermal growth Pancreatic cancer Fatigue
factor receptor
24
 (EGFR).
ATP-

Cell Cycle Control

Regulation of Tumor Suppressor Genes
DRUG MOA USEFULNESS TOXICITY
Bortezomib Reversible inhibitor Multiple Myeloma Myelosuppression,
(Velcade) of 26S Proteosome May improve tumor Peripheral
(Proteases) suppression. neuropathy (30%),
GI upset, Asthenia
Azacytidine Azacytidine is Myelodysplastic Myelosuppression,
incorporated into Syndrome (MDS), Liver toxicity,
DNA and RNA, possible Acute GI toxicity
inhibits Myelogenous
methyltransferase Leukemia (AML)
and demethylates
segments of DNA
and RNA.
Unsuppresses gene
regulation, allows
endogenous
anticancer action.

25