Anti cancer drugs - III

Dr. Jayapriya
The Classification of Anticancer
Drugs
According to
1. chemical structure and resource of the
drug
2. mechanisms of anticancer action
3. cycle or phase specificity of the drug
The Classification of Anticancer
Drugs
 According to chemical structure and
resource of the drug:
Alkylating Agents, Antimetabolite,
Antibiotics, Plant Extracts，Hormones，
Others
The Classification of Anticancer
Drugs
 According to biochemistry mechanisms of
anticancer action:
Block nucleic acid biosynthesis
Direct influence the structure and function of
DNA
Interfere transcription and block RNA synthesis
Interfere protein synthesis and function
Influence hormone homeostasis
Others
The Classification of Anticancer
Drugs
 According to the cycle or phase specificity
of the drug:
cell cycle nonspecific agents (CCNSA)
cell cycle specific agents (CCSA)
SITE OF ACTION OF
ANTICANCER DRUGS
 ALKYLATING AGENTS
1. Nitrogen mustards: mechlorethamine, cyclophosphamide,
ifosfamide, melphalan, chlorambucil
2. Ethylenimines: thio – TEPA, hexamethylmelamine
(altretamine)
3. Alkyl sulfonates: busulfan
4. Nitrosoureas: carmustine, lomustine, estramustine,
bendamustine, streptozocin
5. Triazines: procarbazine, dacarbazine, temozolomide.
6. Platinum compounds: cisplatin, carboplatin, oxaliplatin
2.ANTIMETABOLITES:
Folate antagonist – Methotrexate,
Premetexed, Trimetrexate
Raltitrexed,
Lometrexol.
Purine antagonist – 6 mercaptopurine (adenine),
6 thioguanine (guanine),
Fludarabine,
Cladribine.
Pentostatin (Adenosine deaminase inhibitor)
Pyrimidine antagonist- 5 flurouracil (thymidine),
Gemcitabine (cytosine),
Capecitabine,
Cytarabine.
3. Natural products include

1. Vinca alkaloids – vincristine, vinblastine,

vinorelbine
2. Taxanes – paclitaxel, docetaxel
3. Camptothecins –topotecan, irinotecan
4. Epipodophyllotoxins – etoposide, teniposide
5. Antibiotics
6. Enzymes - L asparaginase.
8. Echinocandins – Yondelis
 Mitotic inhibitors
• Vinca alkaloids
• Taxanes
• Ixabepilone – Microtubule stabilization
Advanced Ca breast resistant to
anthracyclines and taxanes.
• Estramustine – Estrogen + Mechlorethamine
Ca prostate – estrogenic side effects
 Antibiotics
Dactinomycin (Actinomycin D)
Anthracycline derivatives – Daunorubicin
Doxorubicin
Epirubicin
Idarubicin
Valrubicin
Anthracenedione – Mitoxantrone
Bleomycin
Mitomycin
4. Miscellaneous
Hydroxyurea,
Differentiating agents- Tretinoin,
Arsenic trioxide,
5. Targeted drugs
Protein tyrosine kinase inhibitors- Imatinib,
Geftinib,
Erlotinib.
Proteasome inhibitor- Bortizomib
Antiangiogenic- Thalidomide, Lenolidomide
Adrenal cortex suppressant: Mitotane
Biologic response modifiers
 Biological response modifiers
• Interferons
• Interleukins - rIL-2 (Aldesleukin)
• Growth factors:
RBC- Erythropoietin, Darbopoietin,
G CSF- Filgrastim, Pegfilgrastim,
GM CSF- Sargramostim,
Platelets- Oprelvekin
• Tumour necrosis factor TNF
• Monoclonal antibodies:
 Naked MAB : rituximab, alemtuzumab, trastuzumab,cetuximab, bevacizumab
 MAB – Cytotoxic conjugates : gemtuzumab ozogamicin
 Radioimmuno conjugates : tositumomab, ibritumomab tiuxeta

• Immunotoxin – denileukin diftitox

6.Hormones:
Glucocorticoids, Estrogens, Progestins,
Androgens
Antioestrogens:
SERM-Tamoxifen,Tormifene,Raloxifene,
SERD-Fulvestrant
Aromatase inhibitors-
First gen- Aminoglutethimide
Second gen- Formestane,
Fadrazole, Rogletimide,
Third gen- Exemastane, Anastrzole, Letrozole,
Vorozole
 GnRH analogs- Leuprolide,
Goserelin,
Triptorelin,
Buserelin,
GnRH antagonists- Cetrorelix,
Abarelix,
Ganirelix,
Androgen receptor blocker-
Steroidal- Cyproterone,Megestrol,
Nonsteroidal- Flutamide
Nilutamide
Bicalutamide
5 alpha reductase inhibitor-
Finasteride
 ANTHRACYCLINE ANTIBIOTICS :
Doxorubicin (Adriamycin) & Daunorubicin
Tetracycline rings with the sugar daunosamine.
MOA:
• They are similar to alkylating drugs in that they
intercalate between paired bases of double-
stranded DNA, thereby causing uncoiling of
DNA.
• Inhibition of topoisomerase – II
• Generation of free radicals (stimulated by
interaction of doxorubicin with iron )
 ANTHRACYCLINE ANTIBIOTICS

Doxorubicin intercalates
between bases resulting in
uncoiling
Pharmacokinetics : IV.
• These agents imparts a red tinge to the urine.

Toxicity : Irreversible Cardiomyopathy as dilated

cardiomyopathy and heart failure (reduced by α
tocopherol and dexrazoxane and liposomal
preparations)
• Radiation recall reaction

• Uses : Doxorubicin & daunorubicin primarily for acute

leukemias
• Idarubicin and epirubicin – broader activity against
solid tumors - breast, ovary and lung cancer.
DOXORUBICIN ANALOGS:

• MITOXANTRONE:
AML,
Advanced hormone resistant prostate cancer,
Progressive multiple sclerosis.

Less cardiotoxic, may cause APML

• VALRUBICIN:
Intravesical therapy of BCG refractory bladder carcinoma in situ

• EPIRUBICIN:
Adjuvant after resection in early lymph node positive ca breast
 Dactinomycin

• Mode of action : It inhibits DNA

dependent RNA polymerase.
• Toxicity : Bone marrow depression.
• Uses : mainly in Wilms’ tumor and
Choriocarcinoma.
• Radiosensitizer
Bleomycin : Cytotoxic antibiotics
• Mode of action : Free radicals formation and DNA
strand breakage.
• Bleomycin is a CCS drug - G2 phase of the tumor
cell cycle.
• Metabolized by bleo. hydrolase
• Toxicity : Pulmonary fibrosis & cutaneous
reactions
• BM sparing
• Uses : It is used for testicular cancer and
Hodgkin’s disease.
 MITOMYCIN
• Alkylating antibiotic
• Intravesical therapy for superficial bladder
cancers and anal ca. with radiotherapy
• Radiosensitizer - best available drug for
hypoxic tumor cells (converted to alkylating
agent by reduction)
• ADR: HUS, delayed bronchospasm
Highly terato /carcinogenic,
Potentiate cardiotoxicity of anthracyclines.
 L-Asparaginase
• Enzyme that destroys asparagine into
aspartate, needed for protein synthesis
• Leukemia cells deprived of asparagine die.
• Resistance – induction of asparagine
synthetase in tumor cells
• Use – leukemia, lymphomas
• ADR – Hypersensitivity reactions,
acute pancreatitis, cortical vein thrombosis
4. Miscellaneous
Hydroxyurea,
Differentiating agents- Tretinoin,
Arsenic trioxide,
 Hydroxyurea
• Antileukemia, radiation sensitizer, inducer of HbF.
The drug acts in the S phase of the cell cycle by
inhibiting the ribonucleotide reductase, depleting
deoxynucleotides.
• It is used in CML, Sickle cell anemia and AML,
essential thrombocytosis, polycythemia vera.
• Orally
• Only toxicity - myelosuppression.
 DIFFERNTIATING AGENTS
• Tretinoin (ATRA) – Acute PML
ADR: Vit A toxicity, retinoic acid syndrome, CNS
toxicity, hypercholesterolemia, abdominal
pain , diarrhoea
• Arsenic trioxide (As2O3): APML.
Hyperglycemia, prolonged QT interval
5. Targeted drugs
Protein tyrosine kinase inhibitors- Imatinib,
Geftinib,
Erlotinib.
Proteasome inhibitor- Bortizomib
Antiangiogenic- Thalidomide, Lenolidomide
Adrenal cortex suppressant: Mitotane
Biologic response modifiers
 Tyrosine kinase inhibitors -
Imatinib
Trosine kinases – signal transduction pathway –
gene transcription, DNA synthesis
Receptor TK, non receptor TK
Many genes encode TK
Bcr-Abl – CML
c KIT – GIST
PDGFR – CMML, HES
ADR: Edema - pulmonary, pleural & pericardial
effusion,, ascites
EGFR inhibitors: gefitinib, erlotinib
• EGFR belongs to receptor TK family
• EGFR – TK overexpressed in a subset of NSCC
of lung, H & N ca. – dramatic response
• Otherwise low response rate
• Cyp 3A4
• Adr: Diarrhoea, rash, acne
Interstitial lung disease – fatal
 Proteosome inhibitor: bortezomib
• Mediates targeted degradation of proteins
• Bortezomib prevents degradation of
intracellular proteins → signalling cascades
activation → cell cycle arrest → apoptosis
• Refractory and relapsed multiple myeloma
• Diarrhoea, peripheral neuropathy, BM
suppression, fatigue
 Antiangiogenic agents
Thalidomide:
• Inhibits angiogenesis, enhances CMI.
• USES: MM, Melanoma, ENL, SLE skin
manifestations, Crohns dis, Kaposi sarcoma
• ADR: sedation, peripheral neuropathy,
constipation, rash, hypothyroidism, DVT
• IMiDs – immunomodulatory derivatives of
thalidomide – lenalidomide
• Multiple myeloma, myelodysplastic syndrome
• SelCIDs – Selective cytokine inhibitory drugs –
PDE 4 inhi, anti TNF α activity.
• Mitotane – selective atrophy of zona
fasciculata and zona reticularis –
adrenocorticolytic
• Inoperable adrenocortical carcinoma.
 Biological response modifiers
• Interferons
• Interleukins - rIL-2 (Aldesleukin)
• Growth factors:
RBC- Erythropoietin, Darbopoietin,
G CSF- Filgrastim, Pegfilgrastim,
GM CSF- Sargramostim,
Platelets- Oprelvekin
• Tumour necrosis factor TNF
• Monoclonal antibodies:
 Naked MAB : rituximab, alemtuzumab, trastuzumab,cetuximab, bevacizumab
 MAB – Cytotoxic conjugates : gemtuzumab ozogamicin
 Radioimmuno conjugates : tositumomab, 90Y-ibritumomab tiuxetan
 Immunotoxin – denileukin diftitox
Biological response modifiers:

Indirect- enhancing immune response

Direct- on tumour cells
Interferon α:
Hairy cell leukemia,
Condylomata acuminata,
CML,
Kaposi’s sarcoma with AIDS
Interleukin (IL 2):ALDESLEUKIN

Induces & expands a T cell response that is cytolytic for

tumour cells
Short half life – continous IV infusion or multiple
intermittent dosing
USE: Multiple myeloma
Renal cell carcinoma
ADR: Release of cytotoxic lymphocytes in organs and
vessels – hypotension, arrhythmias,
edema, prerenal azotemia,…
Monoclonal antibodies:
MOA: ADCC,
CDCC,
Direct induction of apoptosis
 Monoclonal antibodies
• Rituximab is a monoclonal antibody to a
surface protein, CD-20 on malignant B-
lymphocytes
Use: CLL, Hemolytic anaemia (autoimmune),
ITP, NH Lymphoma, Arthritis (rheumatoid)
• Trastuzumab is a monoclonal antibody to a
surface protein, HER-2 in some breast cancers.
Cardiotoxic.
Trastuzumab
• Alemtuzumab:CD 42 Ag in normal neutrophils,
lymphocytes + T & B cell lymphomas – CLL

• Cetuximab – EGFR, hypersensitivity reactions

• Panitumumab – EGFR - fully human, less
hypersensitivity reactions.
• Bevacizumab – VEGF
Colorectal carcinoma
 MAB – CYTOTOXIC CONJUGATES
GEMTUZUMAB OZOGAMICIN – CD 33 in
haematopoietic cells, AML, myelodysplasias.
Linked to calicheamicin – antitumour antibiotic

Double stranded DNA breaks & cell death.

BM supression, hepatotoxicity – fatal VOD.

 RADIOIMMUNO CONJUGATES
• MAB used to target radioactive particles to
tumor cells
• 131 I tositumomab – γ emission – imaging and
therapy
• hazard to care givers
• 90Ytrium ibritumomab tiuxetan – β emitter,
more effective in large tumours, short t1/2
• Relapsed lymphomas
 IMMUNOTOXIN
DENILEUKIN DIFTITOX:
• r IL 2 with diphtheria toxin
• Use: Cutaneous T cell lymphoma
Combined with bexarotene which
increases CD25 expression on malignant T
cells.
• ADR: Hypersensitivity reactions, vascular leak
syndrome, constitutional toxicities
 COLONY STIMULATING FACTORS
• Helps to use combination therapy or high
dose therapy with diminished complications
 Hormones and antagonists
The growth of some cancers is hormone
dependent. Growth of such cancers can
be inhibited by surgical removal of
hormone glands, increasingly, however,
administration of hormones or
antihormones is preferred.
5.Hormones:
Glucocorticoids, Estrogens, Progestins,
Androgens
Antioestrogens:
SERM - Tamoxifen,Tormifene,Raloxifene,
SERD - Fulvestrant
Aromatase inhibitors-
First gen - Aminoglutethimide
Second gen- Formestane,
Fadrazole, Rogletimide,
Third gen- Exemastane, Anastrzole, Letrozole,
Vorozole
 GnRH analogs- Leuprolide,
Goserelin,
Triptorelin,
Buserelin,
GnRH antagonists- Cetrorelix,
Abarelix,
Ganirelix,
Androgen receptor blocker-
Steroidal- Cyproterone,Megestrol,
Nonsteroidal- Flutamide
Nilutamide
Bicalutamide
5 alpha reductase inhibitor-
Finasteride,
Dutasteride
 Glucocorticoids

Glucocorticoids (mainly prednisone)

Used in cancer chemotherapy for two reasons:

• Lymphotoxic action - lymphocytic leukemia,

lymphomas and multiple myeloma.

• Anti-inflammatory and immunosuppressant

actions - palliative therapy of many different
tumors.
 Estrogens

• Supress LH secretion – testosterone synthesis

• Androgen-dependent metastatic prostatic
carcinoma.
• Diethylstilbestrol is usually the agent of choice.
• ADR: Cardiac and cerebrovascular
complications and carcinoma of
the male breast
 Progestins
DMPA, hydroxy progesterone caproate, megestrol

Metastatic hormone dependent Ca breast and

endometrium.

Also stimulate appetite and restore a sense of well

being in advance cancer and AIDS pts.
 Androgens:
• Androgen activity in breast cancer is similar to
that of estrogens, perhaps for the same
mechanistic reasons.
• Virilizing effects and hepatic toxicity -
unacceptable
• Fluoxymesterone - most widely used agent.
• Danazol - used in aplastic anemia and
congenital anemias.
• CA breast
 Antiandrogens (Androgen deprivation
therapy ADT)
Flutamide, bicalutamide, nilutamide :
Androgen receptor antagonist - prostatic
carcinoma.
ADR : Hot flushes, Gynaecomastia.
Used with GnRH agonists – complete
androgen blockade
 GnRH agonists
Goserelin, nafarelin, leuprolide – down
regulation of GnRH receptors – reversible
pharmacological oophorectomy/orchiectomy
Continous administration – transient
release of LH & FSH – initial flaring of ca
prostate/ca breast foll.by inhibition of release.
Concurrent use of androgen receptor antagonist
ADR: impotence, hot flushes, gynaecomastia,
osteoporosis
 GnRH Antagonists
• Cetrorelix, ganirelix, abarelix

• Ca prostate without risk of initial flaring

Antiestrogen therapy:
ER / PR - positive/unknown
SERM /SERD / AI
Tamoxifene and toremifen – SERM
Fulvestrant - SERD
Exemastane - Aromatase inactivator / suicide substrate
Post menopausal women with ER +ve mammary
carcinoma.
Hot flushes, visual disturbances,
clinical#
 Regimens
• ABVD – Adriamycin, bleomycin, vinblastine,
dacarbazine – Hodgkins lymphoma
• CHOP - R - cyclophosphomide, Hydroxy
daunorubicin (doxorubicin), oncovin (vincristine),
prednisolone – rituximab – non hodgkins lymphoma
• MOPP- Mechlorethamine, oncovin, procarbazine,
prednisolone – Hodgkins lymphoma
• CMF – Cyclophosphamide, Mtx, 5FU
• FOLFOX – 5FU, leucovorin, oxaliplatin – colon cancer
• FOLFIRI – 5FU, leucovorin, irinotecan
• Vorinostat and romidepsin – histone
deacetylase inhibitors – cutaneous T cell
lymphoma.
• Pentostatin – adenosine deaminase inhibitor,
hariy cell leukemia
• Octreotide – ST analog, islet cell carcinoma.
• Plicamycin(mithramycin) – hypercalcemia of
malignancy, metastatic testicular carcinoma
• Zoledronic acid – bony metastasis and
multiple myeloma
Thanks!
Cancer Treatment Others
ALL Vincristine Prednisone Methotrexate
Asparginase Mercaptopurine
Cyclophosphamide
AML Daunorubicin Thioguanine
Cytarabine
CLL Fludarabine Prednisone
Cyclophosphamide Chlorambucil

CML Imatinib Busulfan / Hydroxurea

Hodgkin’s lympoma ABVD MOPP

Non-Hodgkin’s CHOP (Cyclo, Doxo, Vin,

Prednisone)
Cancer Treatment Others

Breast Cyclophosphamide Paclitaxel

Doxorubicin

Bronchogenic Cisplatin Paclitaxel Cyclophosp

cancer Vincristine

Ovarian Cisplatin Paclitaxel Carboplatin

Colorectal Fluorouracil Irinotecan

Testicular Cancer Cisplatin / Etoposide / Vinblastine

Bleomycin (PEB) Doxorubicin

Malignant Dacarbazine Cisplatin

melanoma
 Problems With Cancer
Chemotherapy

• Drug Resistance
• Drug Toxicity
 Drug Resistance

 De novo Resistance
• Acquired Resistance
• Multidrug Resistance (MDR)
 Drug Resistance
De novo resistance:
 De novo resistance can be de novo genetic (i.e. the
cells are initially inherently resistant), or can arise
because drugs are unable to reach the target cells
because of permeability barriers such as the
blood-brain barrier.
 Drug Resistance
Acquired Resistance:
• Acquired drug resistance may result from genomic
mutations, such as the induction or deletion of
enzymes involved in drug inactivation or drug
activation, respectively.
 Drug Resistance
Multidrug Resistance (MDR):
• P-glycoprotein transports many naturally occurring
drugs out of neoplastic cells, and its induction may
lead to multidrug resistance.
• As scientific understanding of the mechanisms of
drug resistance increases, new treatments may be
developed to counteract resistance.
 Drug Toxicity
• The most common toxicities of antineoplastic drugs
result from inhibition of cell replication in the
bone marrow, gastrointestinal epithelium, and hair
follicles. Many antineoplastic drugs also stimulate
the chemoreceptor trigger zone in the medulla and
thereby elicit nausea and vomiting.
 Immunomodulating Drugs

Immunosuppressive Agents:
• Act to suppress immune mechanisms and are used
to treat autoimmune diseases or to prevent graft
rejection following tissue transplantation.

• Ciclosporin, Tacrolimus, adrenocortical hormones,

antimetabolites, alkylating agent, antilymphocyte
globulin, Mycophenolate Mofetil
 Immunomodulating Drugs

Immunopotentiator :
• Enhance antitumor immunity and are used to treat
neoplastic disease.
• Recombinant Interferons and Cytokines.
 Anti-cancer drugs
Mechanisms of resistance :
• Increased DNA repair – alkylating agents
• Formation of trapping agents –increase the
production of thiol trapping agents like glutathione - CCNS.
• Increased cellular inactivation – anti-metabolites
• Decreased activation of prodrugs –anti-
metabolites
• Altered target enzyme – methotrexate and vinca
alkaloids
• Decreased accumulation of drug – Methotrexate
and alkylating agents
 Anti-cancer drugs
Rescue therapy
• Rescue therapy refers to the administration of
drugs to counteract the effect of anticancer
drugs on normal cells.
• Leucovorin after methotrexate therapy
• MESNA with cyclophosphamide therapy
• Dexrazoxane after doxorubicin
• Filgastrim (G-CSF) or sargramostim (GM-
CSF) to prevent chemotherapy-induced
neutropenia
 contd….
• Allopurinol – inhibits xanthine oxidase – prevent hyperurecemia
from tumour lysis
• Rasburicase – recombinant urate oxidase - prevent hyperurecemia
from tumour lysis
• Amifostine – prevent radiation induced xerostomia and cisplatin
induced nephrotoxicity
• Pamidronate and zoledronate – bisphosphonates – for
hypercalcemia of malignancy
• Epoetin alpha, darbopoetin alpha – erythropoeitin – for anaemia
• Oprelvekin – r IL 11 – thrombocytopenia
• Ondansetron – 5HT3 Antag. For CINV (chemo induced nausea n
vomiting)
• APREPITANT – NK 1 Antagonist – for cisplatin induced delayed
vomitin
 Anticancer drugs
Mitotic inhibitors Vinca alkaloids
Taxanes

Topoisomerase I Topotecan
inhibitors Irinotecan

Topoisomerase II Etoposide
inhibitors Tenoposide
(1)destruction of DNA or inhibition of DNA
duplication
– e.g. alkylating agents, mitomycinC
(2) inhibition of nucleic acid (DNA and RNA)
synthesis
– e.g. 5-fluorouracil, 6-mercaptopurine,
methotrexate, cytarabine, etc.
(3) Interfering with the transcription to inhibit RNA
synthesis
– e.g. dactinomycin, dauoruicin, and
doxorubicin
(4) Inhibition of protein synthesis
– e.g. vinca alkaloids, epipodophylotoxins, and
paclitaxel
(5) Interfering with hormone balance
– e.g. adrenal corticosteroids, estrogens,
tamoxifen etc.
Alkylating agents act via a reactive alkyl (RCH2-
CH2+-) group that reacts to form covalent bonds
with nucleic acids.
There follows either cross-linking of the two
strands of DNA, preventing replication, or DNA
breakage.
All alkylating agents are phase –nonspecific , kill
rapidly proliferating cells, also kill
nonproliferating cells.
Antimetabolites are analogues of normal
metabolites and act by competition, replacing
the natural metabolite and then subverting
cellularprocesses.
GTP ATP
6-MP
Thioguanine 6-MP

GMP IMP AMP

IMP dehydrogenase

Ribonucleotide
Hydroxyurea reductase
Fludarabine
dGMP dAMP
INHIBITORS OF PURINE
SYNTHESIS

dGTP dATP

Fludarabine DNA polymerase

Cladribine

DNA DNA
 Aspartate
Carbamoyl P INHIBITORS OF PYRIMIDINE
SYTHESIS
Orotate
PRPP

UMP UTP CTP

Ribonucleotide
Hydroxyurea reductase
Gemcitabine
dUMP
MTTF Thymidylate
THF Fluorouracil dCTP
Synthetase
DHF

dTMP
DNA Cytarabine
DHFR
polymerase

dTTP DNA
Methotrexate

DNA
 Antibiotics

Mitomycin C:
Mechanism:
• Alkylates DNA and thereby causes strand
breakage and inhibition of DNA synthesis.
Indications:
• It is primarily used in combination with
vinvristine as salvage therapy for breast cancer.
Adverse Effects:
• Mitomycin produces delays and prolonged
myelosuppression that preferentially affects
platelets and leukocytes.
 Antibiotics
Bleomycin:
Mechanism:
• The drug has its greatest effect on neoplastic
cell in the G2 phase of the cell replication
cycle.Although bleomycin intercalates DNA, the
major cytotoxicity is believed to result from
ironcatalyzed free radical formation and DNA
strand breakage.
Indications:
• It is useful in Hodgkin’s and non-Hodgkin’s
lymphomas, testicular cancer, and several other
solid tumors.
Adverse Effects:
• Bleomycin produces very little myelosuppression.
The most serious toxicities of Bleomycin are
pulmonary and mucocutaneous reactions.
ANTICANCER ANTIBIOTICS:
Dactinomycin: Steptomyces
Inhibition of RNApolymerases,
Free radical & Topoisomerase 2 mediated.
Use: Rhabdomyosarcoma,
Wilm’s tumour
Toxicity: Proctitis, derm. Manifestations.

Bleomycin: Streptococcus verticillus

Oxidative damage – DNA breakage
IV / IM / Intravesical / sc
Germcell tumour-testis,ovary
Acute fulminant reaction – Test dose essential.
Mitomycin:
Streptococcus caespitosus.
Highly terato /carcinogenic,
Potent radiosensitizer- best available drug –
hypoxic tumour cells.
Potentiate cardio toxicity of anthracyclines.
Anthracyclines:
Streptococcus peucetius
MOA: DNA intercalation
Alteration of fluid& ion transport
Semiquinone mediated cardio toxicity
AML,Kaposi’s sarcoma,lymphoma.
Irreversible cardiomyopathy
 Anti-cancer drugs
Sex hormone inhibitors and
antagonists
Tamoxifen: It is a selective estrogen
receptor modulator, block estrogen
receptor in breast tissue.
• It is used in estrogen receptor positive
breast cancer.
 Anti-cancer drugs

Aromatase inhibitors: Anastrozole

• Anastrozole inhibits aromatase, the
enzyme that catalyzes the conversion of
androstenedione to estrone
• It is used in advanced breast cancer.
 Hormones
Antiestrogen: Tamoxifen
• Tamoxifen is the drug of choice in postmenopausal
women with or recovering from metastatic breast
cancer. It is most effective in patients who have
estrogen receptor-positive tumors.
• Tamoxifen is also used as adjunvctive therapy to
oophorectomy to leuprolide or goserelin in
premenopausal women with estrogen receptor-
positive tumors.
 Hormones
Glucocorticoids:
• They are integral components of curative therapy
for acute lymphoblastic leukemia, non-Hodgkin’s
lymphoma, and Hodgkin’s disease.
• Glucocorticoids have essential roles in the
prevention of allergic reaction, emesis control,
relief of intracranial hypertension or spinal cord
compression in neurologic complications, and pain
relief.
 EPIPODOPHYLLOTOXINS
Etoposide , Teniposide : Late S phase and early G2
phase
Inhibits topoisomerase II
• Topoisomerase II breaks and reseals both strands of
DNA.
→ accumulation of DNA breaks and cell death.
Uses
• Etoposide is used for testicular, lymphoma and lung
cancers.
• Teniposide – ALL
ADR: Acute non lymphocytic leukemia within 1 – 3
yrs of therapy
4.MISCELLANEOUS AGENTS:
L asparaginase:
Standard agent- lymphocytic leukemia
Pegasparagase.
Hydroxyurea:
Antileukemic
Radiation sensitizer
Inducer of fetal Hb in sickle cell disease
Differentiating agents:
Retinoids - ATRA - Acute PML
Arsenic trioxide – upregulates p53 gene
antiangiogenic