PHARMACOLOGY

ANTINEOPLASTICS SHIFT 4
REVIEWER 4.1
REVIEWER | MAY 2020

OUTLINE C. PRINCIPLES OF CANCER TREATMENT

I. Overview of Cancer A. Alkylating Agents  Main objective is to reduce tumor cell population to zero
A. Neoplasm B. Platinum Compounds  Usually uses chemotherapy
B. Carcinogenesis C. Anti-tumor Antibiotics
 Induction phase
C. Principles of Cancer D. Miscellaneous Agents
Treatment IV. Targeted  High doses of combination chemotherapy drugs are given
D. Cell Cycle Chemotherapeutic Agents that so that there are no residual cells after the first cycle
II. Cell Cycle Specific Agents A. Farnesyl Transferase  Consolidation phase
A. Antimetabolites Inhibitors  Several cycles that intends to kill the remaining cells that
B. Hydroxyurea B. Tyrosine Kinase prevents recurrence
C. Microtubulin Inhibitors Inhibitors
 Types of chemotherapy
D. Topoisomerase C. Proteasome Inhibitors
 Neoadjuvant
Inhibitors D. Antibody Therapy
 Given prior to surgery to decrease the size of the tumor for
III. Cell Cycle Non-Specific V. References
it to be excisable
Agents VI. Appendices
 Adjuvant
 Completion after surgery
LEGEND  Direct installation
MUST KNOW SAMPLEX  Administration of chemotherapy drugs in cavities or areas
  cannot be reached by systemic or IV drugs

I. OVERVIEW OF CANCER Gompertzian Kinetics of Tumor Growth

A. NEOPLASM  Cancer cells grow in exponential manner significantly faster in
 “new growth” the early part
 Abnormal mass of tissue with excessive and uncoordinated  Reaches a plateau due to an imbalance between the large
number of cells versus the nutrient of their growth
growth
 Either benign or malignant
Log cell Kill Concept 
 Drugs kill a constant fraction of cells rather than a constant
number of cells with the greatest kill in the first cycle or the
induction phase
 The smaller the volume of the tumor, the better log cell kill
generated
 Greatly reduces residual tumor burden

Goldie-Coldman Model
 Minimize treatment failure due to drug resistance
 Begin treatment as early as possible
 Use multiple non-cross resistant drugs
 Administer cytotoxic drugs as frequently as possible to avoid
tumor cells from recurrence
 Avoid dose modification in anticipation of toxicities of the
drug

Combination Chemotherapy
 No overlapping toxicities
 Does not share the same mechanism of action, instead use
drugs with synergistic effect
 Should be used in their optimal dose schedule
Figure 1. Hallmarks of Cancer. [Dr. Mesina’s ppt]
 Must be given at consistent intervals
B. CARCINOGENESIS  Has clear knowledge regarding the biochemical, molecular, and
 Microscopically, dysplasia in the initial phase, then progresses pharmacokinetic mechanisms of the drugs
into carcinoma in situ, then invasive cancer
D. CELL CYCLE
 Clinically, presents as mass lesions of varying sizes  Has various phases (G1, S-phase, G2, M-phase, G0)
 Normal cell acquires DNA damage through exposure of  G0 phase
environmental carcinogens such as chemicals, radiation, and
 Inactive or resting phase
viruses
 If there is failure of DNA repair, different mutations may occur  G1 phase
leading to alteration of gene products or loss of regulatory gene  Growth phase where synthesis of enzymes needed for
products which in turn leads to malignant neoplasm DNA synthesis happens
 Activation of growth-promoting oncogenes  Has a checkpoint to make sure the cell is big enough or has
 Alterations of genes that regulate apoptosis a suitable environment
 Inactivation of cancer suppressor genes  S-phase
 Synthesis phase
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 DNA is replicated through unwinding by the helicase,  MOA: inhibition of DNA polymerase by mimicking the
complimentary base pairing by DNA polymerase, and structure of cytosine which causes cell death or S-phase
repairing of supercoils by topoisomerase termination of the cell cycle
 G2 phase  Most specific for S-phase
 Route of Administration: IV, intrathecal
 Cell continues to grow as synthesis of cellular components
 Short half-life (7-20 mins)
required for mitosis happen
 Excretion: kidney
 Has another checkpoint to make sure the DNA is replicated  Adverse Effects
 M-phase  Myelosuppression (DLT)
 Mitosis phase  Cerebellar or neurological toxicity (arachnoiditis) in high
 Has four phases doses of intrathecal administration
 Prophase  Indications
o Number of chromosomes doubles  Drug of choice for AML 
 Metaphase
Purine Analogs
o Chromosomes align in the center
 6-Mercaptopurine and 6-Thioguanine
 Anaphase  MOA: activated by HGPRTase to produce non-functional
o Separate towards the opposite poles DNA and RNA leading to inhibition of DNA synthesis
 Telophase (primary); inhibition of phosphoribosylamine synthetase
o Start of cytoplasmic and nuclear division leading to de novo purine synthesis inhibition (secondary)
 S-phase specific
II. CELL CYCLE SPECIFIC AGENTS  Adverse Effects:
A. ANTIMETABOLITES  Myelosuppression (DLT)
 GI and liver toxicity
Methotrexate  Indications:
 MOA: Inhibits dihydrofolate reductase hence, interfering with  ALL
the availability of nucleic acid for DNA synthesis   AML
 S-phase specific  CML
 Well absorbed PO in low doses but decreases PO bioavailability  Fludarabine
in high doses  MOA: inhibits DNA synthesis by incorporating as a false
 Route of administration: PO, IM, IV, SC, intrathecal nucleotide; inhibits DNA polymerase, ligase, and
 Half-life is triphasic primase leading to DNA chain termination
 Excretion: kidneys  S-phase specific
 Adverse effects  Adverse Effects:
 Myelosuppression (dose-limiting toxicity/DLT)  Myelosuppression (DLT)
 Severe mucositis, diarrhea, ulcers, colitis  GI and neurologic toxicity, progressive encephalopathy
 Clinical uses/Indications:  Indications:
 ALL  Single most active agent in treatment of CLL 
 Lymphomas  Lymphomas
 Non-Hodgkin’s lymphoma  Macroglobulinemia
 Solid tumors (breast CA, bladder CA, head and neck CA) B. HYDROXYUREA
 Non-neoplastic (psoriasis, RA, autoimmune diseases)  MOA: inhibits ribonucleotide reductase leading to DNA
 Coupled with Leucovorin/Folinic Acid when given at high synthesis disruption
doses   S-phase specific
 Administered 24-36 hours after MTX infusion  Adverse Effects
 Chemoprotective agent for MTX-induced toxicity  Bone marrow suppression, chiefly leukopenia
 MOA: bypasses the inhibited reductase to form nucleic acids
 GI toxicity
for the normal cells
 Indications
Pyrimidine Analogs  Myeloproliferative diseases (polycythemia vera,
 5-Flurouracil (5-FU) thrombocytosis, blast crisis in AML and CML)
 Inhibits thymidylate synthetase causing disruption of C. MICROTUBULIN INHIBITORS
thymidine synthesis 
 Route of Administration: IV Vinka Alkaloids
 Capecitabine  “VIN-“
 Prodrug of 5-FU given orally  Vincristine, Vinorelbine, Vinblastine
 Metabolism: liver  MOA: prevents polymerization of tubulins leading to
 S-phase specific inhibition of assembly of mitotic spindle
 Adverse effects  M-phase specific
 Myelosuppression (DLT)  Adverse Effects
 GI toxicity  Vincristine
 Indications:  Peripheral neuropathy (DLT)
 Colon CA (principal)   Obstipation and paralytic ileus in high doses
 FOLFOX (5-FU + Oxaliplatin)  Vinorelbine
 FOLFIRI (5-FU + Irinotecan)  Neutropenia (DLT)
 Breast CA, head and neck CA  GI toxicity
 Cytosine arabinoside/Cytarabine (ara-C)  Vinblastine
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 Leukopenia (DLT)  Hypotension due to rapid infusion
 Mucositis in high doses  GI toxicity, peripheral neuropathy
 Indications  Has LEUKEMOGENIC potential 
 Vincristine  Within 1-3 years, patient may present with AML
 ALL, lymphoma, Wilm’s tumor  Indications
 Vinorelbine  Hodgkin’s disease
 Lung CA, breast CA  Lymphomas
 Vinblastine  Leukemia
 Testicular CA, bladder CA, Hodgkin’s disease,  Lung CA, testicular CA, gastric CA
Kaposi’s sarcoma
III. CELL CYCLE NON-SPECIFIC AGENTS
Taxanes A. ALKYLATING AGENTS
 “-TAXEL”  General MOA: insertion of alkyl group to the DNA double
 Paclitaxel and Docetaxel strand which results to cross-linkage and breaks causing DNA
 MOA; binds to beta tubulin leading to stabilization of the damage and induction of cell apoptosis
microtubules preventing disintegration and  Major site of alkylation: N7 position of guanine 
depolymerization resulting to cell death
 M-phase specific  Affects all cells (cycling and resting) but most toxic to rapidly
 Paclitaxel is insoluble in water, thus formulated in castor oil + dividing cells
alcohol (Cremophor-EL)   Has LEUKEMOGENIC potential (4-5 years after treatment) 
 Docetaxel is more soluble in water; does not use Cremophor-
EL Cyclophosphamide
 Route of administration: IV  MOA: Inhibition of DNA replication and RNA transcription
 Metabolism: liver (CYP450) resulting to inhibition of nucleic acid function
 Adverse Effects  Most commonly used alkylating agent
 Paclitaxel  Wide spectrum of anti-tumor activity
 Acute hypersensitivity reactions due to Cremophor-EL  Converted to phosphoramide mustard which exerts the anti-
 cancer effect
 Neutropenia (principal toxicity)  Adverse effects
 Cardiac conduction abnormalities  Myelosuppression (DLT)
 Docetaxel  HEMORRHAGIC CYSTITIS 
 Same as Paclitaxel except the acute hypersensitivity  Due to accumulation of acrolein in the urine and bladder
reactions  Vigorous hydration should be done
 Indications  Antidote: MESNA
 Paclitaxel  Highly emetogenic
 Ovarian CA, breast CA, lung CA, head and neck CA  Pulmonary and cardio toxicity (SIADH, DVT)
 Docetaxel  Infertility and secondary malignancies
 Resistant Breast CA   Indications
 Ovarian CA, head and neck CA, lung CA  Burkitt’s lymphoma, breast CA, non-Hodgkin’s lymphoma
D. TOPOISOMERASE INHIBITORS
Ifosfamide
Topoisomerase I Inhibitors  Same MOA but produces different metabolites (chloroacetic
 “-TECAN” (/tec-one/ for Topoisomerase ONE) acid/chloroacetaldehyde) which is responsible for CNS toxicity
 Irinotecan and Topotecan  Same adverse effects
 MOA: induction of single-strand breaks leading to inhibition  Indications
of DNA synthesis  Lymphoma, ovarian CA, testicular CA
 S-phase specific
 Adverse Effects Melphalan
 Irinotecan  MOA: formation of intra-strand, inter-strand breaks in DNA and
 Diarrhea (principal toxicity) protein cross-links leading to DNA damage
 “Iri” pertains to pooping…  Route of Administration: PO
 Topotecan  Adverse effects
 Myelosuppression (DLT)  Myelosuppression (DLT)
 Indication  Alopecia
 Irinotecan  GI toxicity
 Advanced Colorectal CA   Indication
 Topotecan  Multiple myeloma, ovarian CA, breast CA
 Second-line therapy for advanced ovarian CA 
Chlorambucil
Topoisomerase II Inhibitors  Same as general MOA
 “-POSIDES” (/posi-dos/ for Topoisomerase TWO)  Route of Administration: PO
 Etoposide and Teniposide  Well-tolerated with minimal nausea and vomiting
 MOA: induction of double-strand breaks leading to  Adverse effects
inhibition of DNA synthesis and induction of apoptosis  Myelosuppression (DLT)
 Late S-early G2 phase specific  Liver abnormalities
 Adverse effects  Pulmonary fibrosis
 Myelosuppression (principal toxicity)  Indication
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 CLL  Reduced renal toxicity and myelosupppression
 Non-Hodgkins lymphoma compared to the other -platins
 Indication
Dacarbazine
 Cisplatin
 Classified as methylating agent under non-classical alkylators
 Ovarian CA, testicular CA, lung CA, bladder CA
 Same as general MOA
 Route of Administration: IV  Carboplatin
 Half-life: 5 hours  Same as Cisplatin
 Metabolism: Liver (CYP450)  Oxaliplatin
 Adverse effects  Second-line for metastatic colorectal CA 
 Highly emetogenic 
C. ANTI-TUMOR ANTIBIOTICS
 Myelosuppression is uncommon (DLT)
 Flu-like syndrome, facial flushing, occasional hepatotoxicity Anthracyclines
 Phlebitis and cellulitis  “-RUBICIN” (Doxorubicin, Idarubicin, Epirubicin, Daunorubicin)
 Indication  MOA
 Hodgkins disease  Intercalates DNA that produces interruption of base
 Soft tissue sarcoma pairing
 Malignant melanoma  Inhibits Topoisomerase II leading to DNA synthesis
inhibition
Procarbazine  Binds to cell membranes to alter fluidity and ion
 Classified as methylating agent under non-classical alkylators transport
 MOA: inhibition of DNA, RNA, and protein synthesis  Generates oxygen free radicals
through production of free radicals that cause DNA  Route of Administration: IV
scission  Potent vesicant which can cause blisters and tissue necrosis
 Route of Administration: PO once drug extravasates outside the veins
 Half-life: 10 mins  Half-life 24-48 hours
 Produces “azoprocarbazine” which causes DNA scission  Metabolism: liver
 Adverse effects  Adverse effect
 Myelosuppression (principal toxicity)  CARDIAC TOXICITY (DLT) 
 GI and CNS toxicity  Acute (arrythmias, conduction abnormalities, myocarditis)
 Has leukemogenic potential   Chronic (dilated cardiomyopathy)
 Indication  Occurs when cumulative dose is 450-550mg/m2 of
 Hodgkins disease Daunorubicin
 Non Hodgkins lymphoma  Antidote: Dexrazoxane 
 Lung CA, brain CA o Given when anthracycline dose is >300mg/m2
 Myelosuppression
Thiotepa  Adriamycin Flare (allergic reaction to the drug)
 Alkyl-alkane sulfonate agent  Eryhtematous streaking near the site of injection
 Same as general MOA  Radiation recall reaction
 Lipophilic and can cross BBB  Erythema and desquamation in previously irradiated areas
 Route of Administration: versatile (IV, intracavitary, intravesicle)
 Well-tolerated with minimal nausea and vomiting Bleomycin/Mitomycin/Dactinomycin
 Adverse effects  Bleomycin
 Myelosuppression (DLT)  MOA: oxidation of DNA-bleomycin-ferrous complex that
 Gonadal dysfunction produces toxic free radicals leading to single and
 Mucositis,skin rash, CNS toxicity double stranded DNA breaks resultin to inhibition of
 Indication DNA synthesis and cell death
 Brain CA, bladder CA  Adverse effects
 Conditioning regimen for BM transplant  Pulmonary Fibrosis (DLT)
 Indication
B. PLATINUM COMPOUNDS
 Hodgkins lymphoma
 ”-PLATIN”
 Testicular CA
 MOA: binds to N7 of guanine or adenine producing intra-  Skin CA
strand and inter-strand crosslinks leading to DNA synthesis  Dactinomycin
inhibition  MOA: causes DNA strand breaks by intercalation
 Adverse effect resulting to RNA synthesis inhibition
 Cisplatin  Route of Administration: IV
 Does not enter CSF
 Nephrotoxicity (DLT) 
 Has a phenoxazone structure
 Antidote: Amifostine  Adverse effect
 Severe nausea and vomiting  Myelosuppression especially leukopenia and
 Carboplatin thrombocytopenia (DLT)
 Myelosuppression (DLT)  GI toxicity
 Reduced renal toxicity compared to Cisplatin  Radiant recall reaction
 Oxaliplatin  Indication
 Wilm’s tumor
 Peripheral neuropathy (DLT)  Choriocarcinoma
 Bone CA
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 Mitomycin  Bone marrow stimulant
 Quinine antibitotic  Flutamide and Bicalutamide
 MOA: causes DNA cross linkages leading to DNA  anti-androgen
inhibition  MOA: competes with androgen to the androgen receptor
 Route of Administration: IV resulting to inhibition of androgen uptake and androgen
 Adverse effect binding in the nucleus
 Myelosuppression (DLT)  Route of Administration: PO
 Hemolytic uremic syndrome  Rapidly absorbed in GIT
 Nephrotoxicity  Bicalutamide has 4x affinity to androgen receptors than
 Pulmonary fibrosis Flutamide 
 Indication  Administered with GnRH agonists
 Pancreatic CA  Adverse effect
 Lung CA  Gynecomastia, hot flushes, hepatic dysfunction
 Head and neck CA  Indication
D. MISCELLANEOUS AGENTS  Prostate CA
 Leuoprolide and Goserelin
L-Asparaginase  GnRH agonists
 MOA: conversion of L-asparagine to aspartic acid and  MOA: suppresses gonadotropin secretion of FSH/LH
ammonia will cause depletion of L-asparagine and resulting to decreased levels of androgen and/or
inhibition of protein synthesis estrogen
 Route of Administration: IM, IV  Adverse effects
 Adverse effects  Transient flare of symptoms
 hot flushes
 Acute hypersensitivity reaction
 impotence and gynecomastia
 Skin testing is required prior to administration 
 Indication
 CNS toxicity, pancreatitis  Prostate CA and breast CA
 Alopecia  Aminoglutethimide
 GI toxicity  Aromatase inhibitors
 Indication  MOA: inhibition of aromatase enzyme which converts
 ALL androgen to estrogen through aromatization
 Requires co-administration of hydrocortisone
Endocrine Agents
 Adverse effect
 Works through cytostatic mechanisms thus requiring long term  Dizziness
administration  Rash
 Effects are receptor-mediated   Indication
 Evaluation of tumor’s receptor status is important  Breast CA, prostate CA
 Estrogen  Exemestane
 MOA: inhibition of the growth of prostatic tissue  Irreversible steroidal inhibitor (TYPE 1)
by blocking LH production leading to  MOA: irreversible inhibition of aromatase leading to
decreased androgen synthesis in the testes inhibition of estrogen synthesis
 Adverse effects  Route of administration: PO
 In males: loss of muscle mass, increase body fat, loss of  Metabolism: liver (CYP3A4)
libido
 Advantages over Aminoglutethimide 
 Hypercoagulable state, premature coronary disease,
 More potent
feminization
 More selective
 Indication  no need to supplement with hydrocortisone because it
 Prostate CA only affects the steroidogenesis for sex hormone
 Tamoxifen production and not the mineralocorticoid synthesis
 Anti-estrogen  Adverse effect
 MOA: competitively binds to estrogen receptors in  Hot flushes, fatigue, nausea
cancer cells producing a nuclear complex that  Acne and hair changes
decreases DNA synthesis  Anastrozole and Letrozole
 Adverse effect  Reversible non-steroidal inhibitor (TYPE 2)
 Nausea, hot flushes, vaginal dryness, loss of sexual  MOA: selective non-steroid inhibitor of aromatase
desire leading to inhibition of the conversion of adrenal
 Risk of thromboembolic disease and endometrial CA androgens to estrogen
 Indication  Route of administration: PO
 Breast CA
 Metabolism: liver
 chemoreceptive agent for women at high risk of breast
 Advantages over Aminoglutethimide:
CA with hormone- receptor positive disease
 Same with Exemestane
 Testosterone
 Indication
 MOA: direct physiologic effect on the androgen
 post-menopausal women with metastatic breast CA
receptors located on every tissue especially the breast
that is ER-positive
 Contraindicated in prostatic CA
 Glucocorticoids
 Adverse effect
 Prednisone, Methylprednisolone, Dexamethasone
 Fluid retention, cholestatic jaundice
 MOA: induce cell death by apoptosis
 Virilization
 Lympholytic and non-myelosuppressive
 Indication
 Breast CA with hormone-receptor positive disease  Route of administration: IV, PO, IM
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 Adverse effect Monoclonal Antibodies
 Fluid retention, hyperglycemia, hypokalemia  Laboratory-produced molecules engineered to serve as
 Osteoporosis, immunosuppression, cushingoid substitute antibodies that can restore, enhance, or mimic the
appearance, GI ulcers immune system’s attack on cancer cells
 Indication  Only target cancer cells
 ALL  No or little effect on normal cells
 Lymphomas Table 2. Most common monoclonal antibodies 
IV. TARGETED CHEMOTHERAPEUTIC AGENTS Monoclonal Target Tumor Type
Table 1. Conventional VS Targeted Chemotherapy Antibody
Conventional Targeted  Rituximab  CD20  Non-Hodgkin’s
 Affects cells with high  Affects cancer cell with little lymphoma
doubling time (cancer and off-target side effect  Alemtuzumab  CD52  CLL
normal cells)  Trastuzumab  HER 2  Breast CA
 Not specific  More specific to target cells Immune Checkpoint Inhibitors
 Mostly IV, few PO  Many PO  Cytotoxic T-lymphocyte associated antigen 4 (CTLA4) inhibitor
 Cytotoxic  Cytotoxic and cytostatic  Upregulates T-cell activation against cancer cells
 Programmed cell death protein 1 (PD1) inhibitor
A. FARNESYL TRANSFERASE INHIBITORS
 Activates T-cell function against tumor cells
 MOA: interferes with the RAS signaling mechanism by
inhibiting the enzyme farnesyl transferase which leads to REFERENCES
less mutations in RAS  PowerPoint by Dr. Mesina (2022)
 Adverse effect  Katzung’s Basic and Clinical Pharmacology 14th Edition
 Nausea and vomiting END OF REVIEWER
 Myelosuppression Prepared by: Rayos, Al Kim
SEE THE TABLE OF SUMMARY IN THE NEXT PAGE…
 Fatigue
 Neurotoxicity
 Indication
 Breast CA and melanoma
B. TYROSINE KINASE INHIBITORS
 “-NIB”
 General MOA: inhibits tyrosine kinase enzyme that is
responsible for cell proliferation which in cancer cells is
upregulated

Imatinib or Gleevec
 One of the most successful TKI
 MOA: inhibition of autophosphorylation of BCR-ABL
oncogene leading to reactivation of apoptosis
 Route of Administration: PO
 Resistance may occur from mutation of BCR-ABL gene
 Adverse effect
 Diarrhea, myalgia, fluid retention
 Congestive heart failure
 Indication
 Drug of choice for CML 
C. PROTEASOME INHIBITORS
 Bortezomib
 MOA: inhibits proteasome resulting to accumulation of
regulatory proteins such as apoptosis promoter Bax
 Adverse effect
 Peripheral neuropathy
 GI toxicity (diarrhea)
 Thrombocytopenia
 Indication
 Multiple myeloma
 Plasma cell disorders
D. IMMUNOTHERAPY
 Newest cancer strategy
 Achieved through direct action of an antibody or activating the
immune system
 PHARMACOLOGY

ANTINEOPLASTICS SHIFT 4
REVIEWER 4.1
REVIEWER | MAY 2020

Drug MOA Adverse Effect (DLT) Indication

 Inhibits dihydrofolate  ALL, NHL, solid
 Methotrexate  Myelosuppression
reductase tumors
 Inhibits thymidylate
 5-Flurouracil  Myelosuppression  Colon CA
synthetase
 Inhibits DNA
 Cytarabine polymerase causing  Myelosuppression  AML
cell death
 Inhibition of DNA
synthesis
 ALL, AML
 6-MP and 6-TG  Inhibition of  Myelosuppression
 CML
phosphoribosylamine
synthetase
 inhibits DNA
polymerase, ligase,
 Fludarabine and primase leading  myelosuppression  CLL
to DNA chain
termination
 Inhibits
 Myeloproliferative
 Hydroxyurea ribonucleotide  BM suppression
disease
reductase
 peripheral  ALL, lymphoma,
 Vincristine
 prevents neuropathy Wilm’s tumor
polymerization of  Kaposi’s sarcoma,
tubulins leading to Hodgkin’s
 Vinblastine  Leukopenia
inhibition of disease, testicular
assembly of mitotic and bladder CA
spindle  lung and breast
 Vinorelbine  neutropenia
CA
 Neutropenia
 Prevents
 Acute  Ovarian, breast,
 Paclitaxel disintegration and
hypersensitivity and lung CA
depolymerization of
reactions
microtubules
 resistant breast
 Docetaxel resulting to cell death  neutropenia
CA
 Advanced
 Irinotecan  Diarrhea
 Inhibits colorectal CA
topoisomerase I  advanced ovarian
 Topotecan  myelosuppression
CA
 Hodgkin’s
 Etoposide and  Inhibits disease,
 Myelosuppression
Teniposide topoisomerase II leukemia,
lymphoma
 Burkitt’s
 Insertion of alkyl
 Cyclophosphamide lymphoma, NHL,
group to DNA double  Myelosuppression
breast CA
strand to inhibit  Hemorrhagic cystitis
 Ovarian and
 Ifosfamide nucleic acid function
testicular CA
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 formation of
strand breaks  multiple myeloma,
 Melphalan protein cross-links  myelosuppression ovarian and
leading to DNA breast CA
damage
 Chlorambucil  Insertion of alkyl  Myelosuppression  CLL, NHL
group to DNA double  Hodgkin’s
 Dacarbazine strand causing DNA  Highly emetogenic disease, soft
damage tissue sarcoma
 Produces free  Hodgkin’s
 Procarbazine radicals that causes  Myelosuppression disease, NHL,
DNA scission brain CA
 Brain and bladder
 Insertion of alkyl
CA
group to DNA double
 Thiotepa  Myelosuppression  Conditioning
strand causing DNA
regimen for BM
damage
transplant
 Cisplatin  Binds to N7 of  Nephrotoxicity  Ovarian,
guanine or adenine testicular, lung,
 Carboplatin  Myelosuppression
producing crosslinks and bladder CA
that leads to DNA  Peripheral  Metastatic
 Oxaliplatin
synthesis inhibition neuropathy colorectal CA
 Intercalates DNA
that produces
 Hodgkin’s and
interruption of base
non-Hodgkin’s
pairing
lymphoma
 Anthracyclines  Inhibits
 Cardiac toxicity  Acute leukemias
(-rubicin) Topoisomerase II
 Breast, lung,
leading to DNA
ovarian, and
synthesis inhibition
thyroid CA
 Generates oxygen
free radicals
 Generates free
radicals that causes  Hodgkin’s
 Bleomycin strand breaks  Pulmonary fibrosis lymphoma and
leading to DNA testicular CA
synthesis inhibition
 causes DNA strand
breaks by  Wilm’s tumor,
 Dactinomycin intercalation resulting  thrombocytopenia choriocarcinoma,
to RNA synthesis and bone CA
inhibition
 Causes DNA cross  Pancreatic, lung,
 Mitomycin links leading to DNA  Myelosuppression head and neck
damage CA
 Acute
 Inhibition of protein
 L-asparaginase hypersensitivity  ALL
synthesis
reactions
 blocks LH production
leading to  loss of muscle mass,
 Estrogen decreased androgen increase in body fat,  prostate CA
synthesis in the loss of libido
testes
PHARMA REVIEWER 4.1: Antineoplastics 9 of
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 Breast CA
 Competitive binding
 Nausea, hot flushes,  Preventive agent
to estrogen receptors
 Tamoxifen risk of endometrial for high risk
decreasing DNA
CA hormone- receptor
synthesis
positive disease
 Direct physiologic
 Virilization, fluid  Breast CA
 Testosterone effect on androgen
retention  BM stimulant
receptors
 competes with
androgen to the
 Flutamide and  gynecomastia,
androgen receptor  prostate CA
Bicalutamide hepatic dysfunction
resulting to inhibition
of androgen uptake
 Suppresses release
 Impotence,
 Leuprolide and of FSH/LH resulting  Prostate and
gynecomastia, hot
Goserelin to decreased breast CA
flushes
androgen/estrogen
 Inhibits aromatase  Breast and
 Aminoglutethimide  Dizziness and rash
enzyme prostate CA
 Irreversible inhibition
of aromatase
 Exemestane  Breast CA
resulting to inhibition
 Fatigue, nausea,
of estrogen synthesis
acne, and hair
 Reversible inhibition
changes
 Anastrozole and of aromatase  Metastatic breast
Letrozole resulting to inhibition CA (ER-positive)
of estrogen synthesis
 Immunosuppression,
 Induce cell death by cushingoid
 Glucocorticoids  ALL, lymphomas
apoptosis appearance,
hyperglycemia
 Farnesyl
 Interferes with RAS
transferase  Myelosuppression  Breast CA
signaling mechanism
inhibitors
 inhibition of
autophosphorylation
 Imatinib or of BCR-ABL  diarrhea, myalgia,
 CML
Gleevec oncogene leading to CHF
reactivation of
apoptosis
 inhibits proteasome
resulting to
 multiple myeloma,
accumulation of  peripheral
 Bortezomib plasma cell
regulatory proteins neuropathy
disorders
such as apoptosis
promoter Bax
 Non-Hodgkin’s
 Rituximab  Targets CD20 
lymphoma
 Alemtuzumab  Targets CD52   CLL
 Trastuzumab  Targets HER 2   Breast CA
 PHARMA REVIEWER 4.1: Antineoplastics 10 of
11

UNIVERSITY OF SANTO TOMAS

FACULTY OF MEDICINE AND SURGERY
D2022 Reviewer
Sample EXAMINATION
May 2020

Instructions:
1. There are 20 items in this questionnaire
2. CHOOSE THE BEST ANSWER.
3. Try to answer on your own (without the use of reviewers/trances)
4. Answers are given in a separate document.
5. God bless!

------------------------------------------------------------------------------------------------------------------------------------------ ------------------------
CHOOSE THE BEST ANSWER

MULTIPLE CHOICE.
1. This drug can produce acute hypersensitivity reactions due to its vehicle, Cremophor-EL.
A. Paclitaxel B. Docetaxel C. Vinblastine D. Vincristine

2. Skin testing prior to administration of this drug is required due to hypersensitivity reactions.
A. Bleomycin B. Cisplatin C. L-asparaginase D. Exemestane

3. What antidote is given to a patient who experienced hemorrhagic cystitis after treatment with cyclophosphamide?
A. Dexrazoxane B. MESNA C. Amifostine D. Potion from Quiapo

4. Which drug requires co-administration of hydrocortisone due to its inhibition of the aromatase enzyme necessary
for steroidogenesis?
A. Anastrozole B. Exemestane C. Aminoglutethimide D. Letrozole

5. The chemotherapy undertaken by this patient caused dilated cardiomyopathy. Which drug was most likely
responsible for this toxicity?
A. Daunorubicin B. Methotrexate C. Dacarbazine D. Hydroxyurea

MATCHING TYPE.
MECHANISM OF ACTION
A. Inhibits topoisomerase II
B. Inhibits BCR-ABL oncogene
C. Inhibits thymidylate synthetase
D. Inhibits topoisomerase I

____ 6. Imatinib
____ 7. 5-FU
____ 8. Irinotecan

ADVERSE EFFECT
A. Cisplatin
B. Carboplatin
C. Oxaliplatin

____ 9. Myelosuppression
____10. Nephrotoxicity
____11. Peripheral neuropathy

INDICATION
A. Rituximab
B. Tamoxifen
C. Estrogen
D. Alemtuzumab
E. Cytarabine
 PHARMA REVIEWER 4.1: Antineoplastics 11 of
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____12. CML
____13. Prostate CA
____14. Non-Hodgkin’s lymphoma
____15. Breast CA

PRESCRIPTION
ERASURES MAY BE ALLOWED “BUT” COMPLAINTS ON THE ERASED ANSWER WILL NOT BE ENTERTAINED

16-20: A 59-year old woman presented with a large left breast mass with enlarged axillary lymph nodes. The patient had
ignored the mass for almost a year. A skin biopsy was performed because of breast cancer suspicion. Histopathology
showed a high-grade invasive ductal carcinoma with lymph node metastasis. Molecular analysis showed that the tumor was
triple-positive for ER, PR, and HER2. Which of the following drugs should be used? Make a prescription good for one month.
A. Anastrozole Preparation: 1 mg Tablet
Recommended dose: 1 mg once a day
B. Tamoxifen Preparation: 20mg Tablet
Recommended dose: 20 mg daily as a single dose or in 2 divided doses

AKRR2020

- END OF QUIZ-
GOD BLESS!