Anticancer
Drugs ?
Dr.lokendra Sharma
Associate Professor
Advances in Cancer Chemotherapy
Treatment options of cancer:?
• No Treatment: Before 1940
• Surgery: before 1955
• Radiotherapy: 1955~1965
• Chemotherapy: after 1965
Cell Cycle
Cell Cycle Specific Agents
• Antimetabolites • Bleomycin
• Podophyllin Alkaloids • Plant Alkaloids
Cell Cycle Non-Specific Agents
• Alkylating Agents • Antibiotics
•Cisplatin
Chemotherapy
Cell cycle effects of anticancer drugs
CCS
Drugs
CCS Drugs
CCNS Drugs
G
1- S
Etoposide
Platinum compounds
S
Antimetabolites
Alkylating agents
G
2– M
Bleomycin
Etoposide
(Ref Harrison
17
th/525)
Anthracyclines
Dactinomycin
M
Vinca alkaloids
Taxanes
Ixabepilone
Estramustine
Mitomycin
Camptothecins
Goals of Therapy ?
Cure or induce prolonged
‘remission’
so that all macroscopic and
microscopic features of the cancer
disappear
Acute Lymphoblastic Leukaemia
Wilm`s tumor, Ewing`s sarcoma etc.
In children, Hodgekin`s lymphoma, testicular
teratoma and choriocarcinoma
Goals of Therapy ?
Palliation:
Shrinkage of evident tumour,
Alleviation of symptoms and
prolongation of life
Breast cancer, ovarian cancer,
endometrial carcinoma,
CLL, CML,
Small cell cancer of lung and
Goals of Therapy ?
Insensitive or less sensitive but life
may be prolonged
Cancer esophagus, cancer stomach,
sq. cell carcinoma of lung,
melanoma,
pancreatic cancer,
myeloma,
Aim of Therapy – contd.
• Adjuvant therapy:
– For mopping up of residual cancer cells
including metastases after Surgery,
– Radiation and immunotherapy etc.
• Routinely used now
General Principles
Analogous with Bacterial chemotherapy –
differences are
Selectivity of drugs is limited
No or less defence mechanism – Cytokines
adjuvant now
All malignant cells must be killed to stop
progemy
Subpopulation cells differ in rate of
proliferation and susceptibility to
chemotherapy
General Principles
Drug regimens or combined cycle
therapy after radiation or surgery
Complete remission should be the
goal
Formerly single drug – now 2-5
drugs in intermittent pulses
Total tumour cell kill –
COMBINATION CHEMOTHERAPY
- SYNERGISTIC ?
Drugs which are effective when used
alone
Different mechanism of action
Differing toxicities
Different mechanism of toxicities
Synergistic biochemical interactions
Optimal schedule by trial and error
method
Classification ?
According to chemical structure and sources of drugs
– Alkylating Agents, Antimetabolite, Antibiotics, Plant Extracts,
Hormones and Others
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
According to the cycle or phase specificity of the drug:
– Cell cycle nonspecific agents (CCNSA) & Cell cycle specific agents
(CCSA)
Block nucleic acid (DNA, RNA)
biosynthesis
Antimetabolites:
• Folic Acid Antagonist: inhibit dihydrofolate
reductase (methotrexate)
• Pyrimidine Antagonist: inhibit thymidylate
synthetase (fluorouracil) ; inhibit DNA polymerase
(cytarabine)
• Purine Antagonist: inhibit interconversion of purine
nucleotide (6-mercaptopurine and 6-Thioguanine)
• Ribonucleoside Diphosphate Reductase
Influence :Structure & Function of
DNA
• Alkylating Agent: mechlorethamine,
cyclophosphamide, ifosfamide, chlorambucil,
Mephalan, Busulfan, Nitrosoureas and Thio-TEPA
• Platinum: cis-platinium, carboplatin and
imatinib
• Antibiotic: bleomycin and mitomycin C
• Topoismerase inhibitor: camptothecin
analogues and podophyllotoxin and antibiotics
like actinomycin D, daunorubicin and
Sites of Antineoplastic Action ?
Clinical Considerations ?
Early intensive start …. helpful
Complete remission….. goal
Combined chemotherapy useful
…..delayed emergence of resistance
Combined chemotherapy …..curative
Treatment must continue past the
time when cancer cells can be
detected using conventional
techniques
Resistance ?
Intrinsic:
malignant melanoma, renal cell cancer, and
brain cancer, exhibit primary resistance
Acquired:
Single drug:
change in the genetic apparatus amplification or
increased expression of one or more specific
genes
Multidrug resistance:
Resistance variety of drugs exposure to a single variety of drug
increased expression of a normal gene (the MDR1 gene) for a cell surface glycoprotein (P-glycoprotein) involved in drug efflux
Toxicities ?
Harmful to normal tissues too
Steep dose response curve
Low therapeutic index
Particularly harmful to rapidly
multiplying normal tissues: GI
mucosa, Bone Marrow, RE system and
gonads and hair cells
Toxicities ?
Bone marrow depression – limits treatment
Buccal mucosa erosion – high epithelial turnover
(stomatitis, bleeding gums)
GIT: Diarrhoea, shedding of mucosa, haemorrhage
Nausea, vomiting – CTZ direct stimulation
Skin: alopecia
Gonads: oligospermia, impotence, amenorrhoea
and infertility
Lymphoreticular system: Lymphocytopenia and
inhibition of lymphocyte function – loss of host
defense mechanism – susceptibility to infections
Carcinogenicity
Distinctive Toxicities of Alkylating Agents ?
Drug
Toxicity
Cyclophosphamide
Alopecia, Hemorrhage cystitis, SIADH
Ifosfamide
Hemorrhagic cystitis, SIADH
Busulfan
Pulmonary fibrosis, Hyper pigmentation,
Adrenal insufficiency
Procarbazine
Secondary leukemias, Disulfiram like
reaction, behavioral changes, CNS
depression
Cisplatin
Emesis, Nephrotoxicity, Peripheral
sensory neuropathy, ototoxicity
Countering the Toxicities ?
Intermittent therapy
Folinic acid rescue
Systemic Mesna (sodium-2-mercaptoethane
sulfonate) administration and irrigation by
acetylcysteine – detoxify toxic metabolites
Ondansetron
Hyperurecaemia: uricosuric agents like
allopurinol
Platelet and granulocyte transfusion
Granulocyte colony stimulating factors
(GM-CSF/G-CSF) – recovery of garnulocytopenia
Drugs used to prevent toxicity of Anti cancer drugs
Drug Mechanism Indications
Allopurinol Inhibit xanthine oxidase Prevent hyperuricemia from tumor lysis syndrome
Rasburicase Recombinant urate oxidase Prevent hyperuricemia from lysis Mesna Neutralizing agent Prevent hemorrhagic cystitis due to
ifosfamide and high dose cyclophosphamide
Leucovoring Replete Tetrahydrofolic acid Rescue after high dose methotrexate Amifostine Prevent radiation induced
xerostomia and Prevent radiation induced xerostomia and cisplatin induced nephrotoxicity
Dexrazoxane Iron chelator Prevent cardiotoxicity due to anthracyclines
Palifermin Keratinocyte growth factor Prevent mucositis following chemotherapy
Pilocarpine Cholinergic agonist Radiation induced xerostomia Pamidronate and
Drugs used to prevent toxicity of
Anti cancer drugs
Drug Mechanism Indications
Epoetin alpha and darbopoetin alpha
Erythropoietin Anemia
Filgrastim,
peg-filgrastim G-CSF and Febrile neutropenia prophylaxis Sargramostim GM - CHF
Oprelvekin IL-11 Thrombocytopenia Ondansetron 5-HT3 antagonist Nausea and vomiting
Granisetron Palonosetron
Interfere Protein Synthesis
Antitubulin:
vinca alkaloids (vincristine and
vinblastin) and taxanes (paclitaxel and
docetaxel)
Bind tubulin, destroy spindle to produce
mitotic arrest
Influence amino acid supply:
L-asparaginase
Some Alkylating Agents used in cancer Chemotherapy
Agent Route of
Admin. Cancer where preferred Delayed Toxicity 1. Busulphan Oral CML, PV BMD, bleeding, skin
pigmentation adrenal insufficiency, pulmonary fibrosis
2. chlorambucil Oral CLL, PV BMD, bleeding 3.
Cyclophosphamide Oral, i.v All, NHL, PV, Carcinoid tumour, Neurobalstoma BMD, bleeding, hemorrhagic, cystitis 4. Melphalan Oral Multiple myeloma BMD, Bleeding
5. Mechlorethamine i.v. Hodgkin’s disease BMD, alopecia, Diarrhea oral ulcer leukaemia
6. Cisplatin i.v. CA tests, ovary, cervix, lung, head & neck, thyroid,
Melanoma
Renal damage, ototoxicity, neuropathy, BMD
7. Dacarbazine i.v. Melanoma, Hodgkin’s disease BMD 8. Carmustine
(BCNU) i.v. Brain tumours Leukopaenia, thrombocytopaenia 9. Lomustine
(CCNU) Oral Brain tumours Leukopaenia, thrombocytopaenia 10. Thiotepa i.v. CA bladder (early) & Ovary BMD
Tyrosine Kinase Inhibitors
Drug Inhibit TK activated Indication
Axitinib VEGFR – 1,2,3 Advanced renal cell carcinoma Bosutinib Abl –bcr, src CML
Crizotinib c-MET, ALK Non small cell lung carcinoma Cabozantinib c-MET, VEGFR-2 Medullary carcinoma thyroid
Dasatinib abl -bcr CML
Erlotinib EGFR Non small cell lung carcinoma Pancreatic carcinoma
Geftinib abl-bcr, c- KIT, PDGF Non small cell lung carcinoma Imatinib her-2/neu, erb-B2 CML GIST
Lapatinib abl-bcr Breast carcinoma Nilotinib VEGFR-1,2,3 PDGFR α β
c-KIT
CML
Tyrosine Kinase Inhibitors
Drug Inhibit TK activated Indication
Regorafenib VDGFR2, TIE2 Colorectal carcinoma GIST Ruxolitinib JAK 1,2 Myelofibrosis
Sorafenib VEGFR, PDGFR RAF Renal cell carcinoma Hepatocellular carcinoma Sunitinib VEGFR, PDGFR c- KIT, FLT-3 RET Renal cell carcinoma,
Pancreatic neuroendocrine tumors GIST
Tofacitinib JAK Rheumatoid arthritis Vandetanib VEGFR, EGFR Medullary carcinoma
thyroid
Monoclonal Antibodies
S.
No. Monoclonal antibody Targeted against Indication Comments 1 Rituximab CD - 20 Non hodgkin lymphoma
2 Alemtuzumab CD - 52 Low grade lymphomas and CLL
3 Trastuzumab HER 2/neu Breast Carcinoma Can cause cardiotoxicity 4 Cetuximab and
panitumumab EGFR EGFR – positive metastatic colorectal carcinoma Cause rash, Hypomagnesemia and tnterstitial lung
disease 5 Bevacizumab VEGF Metastatic colorectal
carcinoma Combined with 5 - FU 6 Gemtuzumab CD-33 CD-33 Positive AML Linked to
calicheamicin 7 I131 – Tositumomab
Y90 – Ibritumomab
tiuxetan
CD-20 Relapsed lymphomas Conjugated with radioisotopes 8 Denileukin diftitox - Recurrentcutaneous T-cell
Therapy of choice for various cancers
S. No. Diagnosis Treatment of choice1 All Induction: Vincristine + Prednisolone+Daunorubicin+ Asparaginase+Intrathecal Methotrexate
Consolidation: Hyper-CVAD alternated with cytarabine+Methotrexate
2 AML Cytarabine+Daunorubicin/Idarubicin
3 CML Imatinib
4 CLL FCR or Fludarabine 5 Hairy cell leukemia Cladribine
6 Hodgkin disease ABVD 7 Non hodgkin
lymphoma CHOP-R
8 Multiple Myeloma Bortezomib+Dexamethasone+Lenalidomide 9 Waldenstrom
macroglobulinemia FCR
Therapy of choice for various cancers
S. No. Diagnosis Treatment of choice11 Non small cell lung
cancer Cisplatin + Vinorelbine ± Bevacizumab 12 Small cell lung
cancer Cisplatin + Etoposide 13 Mesothelioma Cisplatin + Pemetrexed 14 Head and neck cancer Cisplatin + 5-FU
Some antimetabolites used in cancer chemotherapy
Agent Route of admin. Cancer (s) where preferred Delayed toxicity1. Cytarabine i.v. AML BMD, nausea, Vomiting stomatitis ataxia
(cerevellar) 2. 5- Fluorouracil i.v. Carcinoma head &
neck, Stomach colon, breast
BMD, Oral and GI ulceration, nausea, diarrhoea,
neurotoxicity, *hand and foot syndrome 3. 6-
Mercaptopuine Oral All BMD, Hyperuricaemia, immunosuppression, hepatotoxicity
4. Methotrexate Oral All, choriocarcinoma,
osteogenic sarcoma BMD, vomiting, oral & GI ulcers hepatotoxicity (acute & chronic)
Some natural products in cancer chemotherapy
Agent Cancer (s) where preferred Delayed toxicity
Antibiotics
1. Bleomycin Carcinoma testis, malignant
effusion (intracavity) Alopecia, oedema of hand, pulomonary fibrosis, stomatitis 2. Dactinomycin Wilm’s tumour Alopecia, BMD, Stomatitis, Oral
ulcer
3. Daunorubicin AML Alopecia, BMD, Cardiomyopathy 4. Doxorubicin HL, NHL, neuroblastoma,
Carcinoma thyroid, stomach, carcinoid tumouir, sarcomas, osteogenic sarcoma
Alopecia, BMD, Cardiomyopathy, stomatitis
5. Mitomycin Carcinoma stomach Thrombocytopaenia, leukopaenia 6. Streptozotocin
(sreptozocin) Insulinoma Renal damage, hypoglycaemia, hyperglycaemia, liver damage, BMD, fever eosinophilia,
Some natural products in cancer chemotherapy
Agent Cancer (s) where
preferred Delayed toxicity
Plant Alkaloids
1. Docetaxel Advance case of
carcinoma breast Neurotoxicity, fluid retention, neutropaenia 2. Etoposide Carcinoma testis,
choriocarcinoma
Alopecia, BMD
3. Paclitaxel Carcinoma breast, ovary BMD, peripheral neuritis
4. Vinblastine HD Alopecia, BMD, Loss of reflex 5. Vincristine ALL, NHL Alopecia, BMD, Peripheral
neuritis
6. Vinorelbine Carcinoma lung BMD, fatigue, constipation, hyporeflexia paresthesia
Miscellaneous agents including monoclonal antibodies in cancer chemotherapy
Agent Route of admin. Cancer(s) where used Delayed toxicity
1. Asparaginase i.v. All in child Hepatotoxicity, mental depression,
pancreatitis 2. Cisplatin i.v. CA testis, ovary,
cervix, lung, head & neck, thyroid,
melanoma
Renal damage,
otoxicity neuropathy, BMD
3. Hydroxyurea Oral CML, AML (blast
crisis) BMD
4. Mitotane Oral Adrenocortical
carcinoma Adrenal insufficiency, diarrhoea, lethargy, skin rash (transient) 5. Mitoxantrone Oral Aml BMD, cardiotoxicity,
alopecia 6. Imatinib Oral CML (chronic phase)
& blast crisis Fluid retention (periorbital and ankle oedema), diarrhoea, myalgia
7. Trastuzumab i.v. Carcinoma breast
(metaastatic) BMD, cardiomyopathy, pulm. Toxicity, cardiac
Hormones, their antagonists and related agents in
cancer chemotherapy
Agent Route of admin Cancer(s) where
preferred Delayed toxicity Corticosteroids
Hydrocortisone Prednisone
Oral
Oral All, CLL, NHL, HL Multiple myeloma Fluid retention,Hypertension, diabetes mellitus, susceptibility to infection, moon face
Androgens
Testosterone i.m. Premenopausal breast cancer (oestrogen receptor positive) Fluid retention masculinization Oestrogens Diethylstilboesterol Ethinyloestradiol Oral
Oral Carcinoma prostate,Postmenopausal breast cancer (oestrogen receptors negative) Feminization, Fluid retention Progestins Hydroxyprogesterone Medroxyprogesterone i.m.
Influence hormone
homeostasis
Estrogens and estrogen antagonistic drug
(EE, SERM-tamoxifene)
Androgens and androgen antagonistic
drug (flutamide and bicalutamide)
Progestogen drug (hydroxyprogesterone)
Glucocorticoid drug (prednisolone and
others)
Gonadotropin-releasing hormone
inhibitor: nafarelin, triptorelin
aromatase inhibitor: Letrozole and
Hormones, their antagonists and related agents in
cancer chemotherapy
Agent Route of admin Cancer(s) where
preferred Delayed toxicity Antiandrogen
Flutamide Oral Carcinoma prostate None
Antiandrogen
Tamoxifen Oral Carcinoma breast (early stage, metastatic after surgery)
None
Others GnRH Agonist Goserelin
Leuprolide s.c)s.c.)
Carcinoma prostate None
Aromatase Nhibitors
Aminogulutethimide Oral Metastatic breast cancer None Peptide hormone
Choice of drug in some malignancies where the response of chemotherapy is very good
Cancer Treatment of choice
1. Acute lymphocytic leukaemia Induction: Vincristine + presnisone
Maintenance: Methotrexate + Mercaptopurine + Cyclophosphamide
2. Hodgkin’s disease stage I and II
Stage III and IV RadiotherapyDoxorubicin +
bleomycin+vinblastine+dacarbazine
3. Non Hodgkin’s disease Cyclophosphamide + doxorubicin + vincristine + prednisolone
4. Choriocarcinoma Methotrexate + folic acid or cisplatin + etoposide 5. Cancer testis Bleomycin + cisplatin+ etoposide
6. Wilm’s tumour Surgery + radiotherapy followed by vincristine + dactinomycin
Choice of drug in some malignancies where the
response of chemotherapy is good
Cancer
Treatment of choice
1. Acute myeloid leukaemia Cytarabine + idarubicin/daunorubicin 2. Chronic lymphocytic
leukaemia Chlorambucil + prednisone (if indicated) + fludarabine or cytarabine alone or in combination with other drugs
3. Chronic myelogenous
leukaemia Busulfan or interferon, imatinib (bone marrow transplatation in selected patients) 4. Multiple myeloma Melphalan + prednisone
5. * Carcinoma breast stage 1 Tomoxifen after breast surgery 6. Endometrial carcinoma Progestins or tamoxifen
7. Carcinoma cervix Radiation + cisplatin (localized), cisplatin/carboplatin (metastatic)
8. Carcinoma prostate GnRh agonist or oestrogen + androgen anatagonist (flutamide)
Choice of drug in some malignancies where the
response of chemotherapy is average
Cancer Treatment of choice 1. Carcinoma breast stage II to
IV Cyclophosphamide + methotrexate + 5-FU or Transtuzumab + prednisone + antioestrogen 2. Carcinoma ovary Cisplatin or carboplatin + paclitaxel + interferom 3. Carcinoma thyroid Radioidine (I131), doxorubicin, cisplatin
4. Carcinoma stomach 5-FU + doxorubicin + mitomycin 5. Carcinoma colon 5-FU + leucovorin + irinotecan
6. Osteogenic sarcoma Doxorubicin or methotrexate with leucovorin after surgery
Choice of drug in some malignancies where the
response of chemotherapy in unsatisfactory
Cancer
Treatment of choice
1. Carcinoma lung
Etopise + cisplatin, vinorelbine
2. Carcinoma head and
neck
5-fu+cisplatin or cisplatin + paclitaxel
3. Carcinoma adrenal
gland
Mitotane
4. Carcinoid tumour
Doxorubicin + cyclophospamide or
5-FU + octreotide
5. Polycythaemia vera
Busulfan, chlorambucil or
cyclophospamide
Alkylating Agents
Mechanism of Action:
• Nitrogen mustards inhibit cell reproduction
binding irreversibly nucleic acids (DNA)
• After alkylation, DNA is unable to replicate
• no synthesize proteins and essential cell
metabolites
• Consequently, cell reproduction inhibited cell
eventually dies inability maintain metabolic
functions.
Nitrogen Mustards
• Mechlorethamine:
– Uses: IV
– MOPP (Mechlorethamine – oncovine-prednisolone and procarbazine) in Hodgekin`s lymphoma and disease – ADRs: Severe Vomiting, myelo and immunosuppression – Extravasation – severe local toxicity
• Cycolphosphamide:
– Transformed active aldophosphamide and phospharamide
– orally
– Used Hodgkin's lymphoma, breast and ovary cancers – Ifosphamide longer half life and used mainly testicular
Nitrogen Mustards – contd.
• Chlorambucil: orally, active against
lymphoid tissues (Ch. Lymphatic leukaemia
and non-Hodgkin's lymphoma)
• Busulfan: orally, active against CML
• Carmustine: IV, effective against brain
tumors and Hodgkin's lymphoma
• Dacarbazine: Different from other alkylating
agents – action against RNA and protein
synthesis
Antimetabolites
Folic acid Antagonists: MTX
Purine Antagonists: 6MP and 6TG
Pyrimidine
Antagonists:
5FU
and
cytarabine
General Characteristics:
Antimetabolites S phase-specific drugs
structural analogues of essential metabolites and
that interfere with DNA synthesis.
Methotrexate – Folate
Antagonist
• MOA:
– Structures MTX and folic acid similar
– MTX actively transported mammalian cells and
inhibits dihydrofolate reductase
– the enzyme that normally converts dietary folate
to the tetrahydrofolate form required for thymidine
and purine synthesis
• Leucovorin rescue:
– Administered as a plan in MTX therapy
– Leucovorin (Folinic acid) is directly converted to
tetrahydrofolic acid - production of DNA cellular
protein inspite of presence of MTX
Methotrexate – contd.
• Kinetics:
– orally/IM /IV intrathecally , good oral
absorption
– CSF entry - intrathecal
• Indications:
– Choriocarinoma - was the first demonstration of curative chemotherapy
– Tumors of head and neck – Breast cancer
– Acue lymphatic leukemia
Purine Antagonists
– 6MP,
6TG
6-Mercapapurine (6-MP) and others
• Exact mechanisms uncertain
– inhibit
purine base synthesis
• Used in childhood Acute lymphatic
Leukaemia for maintenance and remission
• combination MTX choriocarcinoma
• Metabolized xanthine oxidase (inhibited
by allopurinol) and allopurinol dose has to
be adjusted to
½ or 1/4
th• Well tolerated, mild myelosuppression ,
Antimetabolites (Pyrimidine
Antagonists) - 5 FU
• MOA:
– Fluorouracil analogue of thymine
– Converted to 5-fluoro-2deoxy-uridine
monophosphate (5-FdUMP)
– 5-FdUMP inhibits thymidylate synthase and
blocks conversion of deoxyuridilic acid to
deoxythymidylic acid
– failure of DNA
synthesis
• Indications: solid tumors, especially
breast, colorectal, and gastric tumors
and squamous cell tumors of the head
and neck
Antibiotics
• Anthracyclines (doxorubicin and dau norubicin), Dactinomycin, Bleomycin, and mitomycin
• Anthracyclines:
– Enters themselves into DNA and causes DNA break – Activates TopoisomeraseII and cause break in DNA
strands
– Generates excess free radicals causing production of superoxide – damage to DNA
– Known to damage cardiac cells also (unique)
– Resistance developes due to increased eflux of drug – Uses: Doxo- Breast, ovary, lung, [prostate and acute
lymphatic leukaemia – Dauno- ALL and AML
1. Which of the following is a radioprotector?
a. Colony stimulating factor
b. Amifostine
c. Cisplatin
d. Methotrexate
(b)
2. Topical mitomycin-C is used in
a. Sturge-Weber syndrome
b. Laryngotracheal stenosis
c. Endoscopic angiofibroma
d. Skull base osteomyelitis
3. Which group of anticancer drugs Temozolomide belong to a. Oral alkylating agent
b. Antitumor Antibiotic c. Antimetabolite
d. Mitotic Spindle Inhibitor (a)
4. Methotrexate is used for the management of all of these conditions except a. Rheumatoid arthritis
b. Psoriasis
c. Sickle cell anemia d. Organ transplantation
5. Which of the following drug is used for the is treatment of sickle cell anemia? a.Hydroxyurea b. Cisplatin c. Paclitaxel d. Carboplatin (a)
6. Use of tamoxifen in carcinoma of breast patients does not lead to the following side effects
a. Thromboembolic events b. Endometrial carcinoma c. Cataract
d. Cancer in opposite breast (d)
7. All of the following are true regarding ifosfamide EXCEPT a. Metabolised by cytochrome p450 enzymes
b. Less neurotoxic than cyclophosphamide
c. Chloracetaldehyde is the metabolite of ifosfamide d. It is a nitrogen mustard
(b)
8. Alkalinisation of urine ameliorates the toxicity of which of the following drugs? a. Arabinoside-cytosine
b. Ifosfamide c. Cisplatin
d. Methotrexate (d)
11. Pulmonary fibrosis is seen with a. Bleomycin b. Cisplatin c. Methotrexate d. Actinomycin D (a)
12. Which of the following drug is used in the treatment of estrogen dependent breast carcinoma?
a. Tamoxifen b. Methotrexate c. Paclitaxel
13. Methotrexate resistance is due to: a. Depletion of Folate
b. Overproduction of DHFRase
c. Overproduction of Thymidylate kinase d. Decreased DHFRase
(b)
14. Hemorrhagic cystitis is caused by a. Cyclophosphamide
b. 6 Mercaptopurine c. 5 Fluorouracil d. Busulfan
15. Thalidomide is used in all of the following except a. HIV associated peripheral neuropathy
b. HIV associated aphthous (mouth) ulcers c. Behcet syndrome
d. Erythema Nodosum Leprosum (a)
16. Most common dose-limiting toxicity of cancer chemotherapy is a. Gastrointestinal toxicity
b. Neurotoxicity
c. Bone marrow suppression d. Nephrotoxicity
17. Which of the following parameters is not monitored in a patient on methotrexate therapy?
a. Liver function tests b. Lung function test c. Eye examination d. Hemogramz
(c)
18. All of the following are true about thalidomide except
a. Used in pregnancy as anti-emetic but withdrawn due to teratogenicity
b. Can be used in multiple myeloma as primary treat ment as well as in refractory disease c. Causes euphoria and diarrhea
d. Can be used in erythema nodosum leprosum (c)
19. Which of the following drug acts by inhibiting tyrosine kinase activated by EGF receptor as well as HER2?
a. Imatinib b. Geftinib c. Erlotinib d. Lapatinib
(d)
20. Tyrosine kinase inhibitors are first line treatment in a. Gastrointestinal stromal tumors
b. Receptor mediated neuroendocrine tumors c. Breast cancer
d. Renal cell carcinoma (a)
• 21. Drug locally used for tracheal stenosis is a. Mitomycin C b. Doxorubicin c. Bleomycin d. Clindamycin (a)
22. Cetuximab (an EGFR antagonist) can be used in a. Palliation in head and neck cancer
b. Anal canal carcinoma c. Gastric carcinoma d. Lung carcinoma
23. Most emetogenic anticancer drug is a. Cisplatin
b. Carboplatin
c. High dose cyclophosphamide d. High dose methotrexate
(a)
24. Cerebellar toxicity is seen with a. Cisplatin
b. Cytarabine c. Bleomycin
d. Actinomycin D (b)
25. All are alkylating agents, except a. 5-Fluorouracil b. Melphalan c. Cyclophosphamide d. Chlorambucil (a)
26. Which of the following can be given orally? a. Cytosine arabinoside
b. Cisplatin c. Doxorubicin d. Mesna
27. In treatment of osteosarcoma, all of the following are used EXCEPT a. High dose methotrexate
b. Cyclophosphamide c. Vincristine
d. Doxorubicin (c)
28. 'Hand and Foot' syndrome can be caused by a. Cisplatin
b. Vincristine c. Capecitabine d. Mitomycin-C
29. Which of the following anti-cancer drugs is cell cycle specific? a. Ifosfamide b. Melphalan c. Vinblastine d. Cyclophosphamide (c)
30. Topical mitomycin-C is used in a. Sturge-Weber syndrome
b. Laryngotracheal stenosis c. Endoscopic angiofibroma d. Skull base osteomyelitis
31. Amifostine is protective to all EXCEPT a. Salivary glands b. Skin c. CNS d. GIT (c)
32. Bleomycin toxicity affects which type of cells a. Type-I pneumocytes
b. Type-II pneumocytes c. Endothelial cells
d. Pulmonary alveolar macrophages (b)
33. SIADH is caused by all EXCEPT a. Vincristine b. Vinblastine c. Actinomycin D d. Cyclophosphamide (c)
34. Imatinib is used in the treatment of? a. Chronic myelomonocytic leukemia b. Myelodysplastic syndrome
c. Acute lymphoid leukemia
d. Gastro intestinal stromal tumors (d)
35. Sustained neutropenia is seen with? a. Vinblastine b. Cisplatin c. Carmustine d. Cyclophosphamide (c)
36. Rituximab is used in all EXCEPT a. Non Hodgkin lymphoma
b. Paroxysomal nocturnal hemoglobinurea c. Rheumatoid arthritis
d. Systemic lupus erythematosis (b)
39. Which of the following anticancer drug is excreted by lungs? a. 5-Fluorouracil b. Cyclophosphamide c. Doxorubicin d. Cisplatin (a)
40. Which of the following drugs is used for the treatment of refractoty histiocytosis?
a. High dose methotrexate b. High dose cytarabine c. Cladribine
d. Fludarabine (c)
41. Thalidomide, used for multiple myeloma, is a. Associated with diarrhea
b. Characterized by enantiomeric intercon-versions c. Metabolized extensively by hepatic CYP system d. Safe for use in pregnant females
(b)
42. A patient on treatment for leukemia, develops chest pain, pulmonary infiltrates and pleural effusion. The likely causeis.
a. Daunorubicin b. Hydroxyurea c. Cytarabine d. Tretinoin
43. Mechanism of action of paclitaxel is a. Topoisomerase inhibition
b. Increases the polymerization of tubulin c. Inhibits protein synthesis
d. Alkylation of DNA (b)
44. Which antineoplastic drug is a peptide? a. Bleomycin
b. Asparteme c. Valinomycin d. Dactinomycin
45. Leucovorin is used to decrease the toxicity of
a. Methotrexate
b. Mercaptopurine
c. Thio-TEPA
d. Cytosine arabinoside
(a)
46. All-trans-retinoic acid is used in treatment of
a. Acute promyelocytic leukemia
b. A.L.L.
c. CML
d. Transient myeloproliferative disorder
(a)
47. Treatment of choice for chronic myeloid leukemia is a. Imatinib b. Hydroxyl-urea c. Interferon-alpha d. Cytarabine (a)
48. Which of the following anticancer drugs can cause hypercoagulable state? a. 5-FU
b. L-asparaginase c. Melphalan
d. Carmustine (b)
49. Anticancer drug causing SIADH as an adverse effect is a. Vincristine b. Paclitaxel c. Dacarbazine d. Cyclophosphamide (a)
50. Which of the following anticancer drugs acts by hypomethylation? a. Gemcitabine
b. 5-FU
c. Decitabine
d. Homoharringotonine (c)
51. High dose methotrexate is used for the treatment of a. Osteosarcoma b. Rhabdomyosarcoma c. Retinoblastoma d. Ewing's sarcoma (a)
52. Which of the following drugs is topoisomerase 1 inhibitor? a. Doxorubicin
b. Irinotecan c. Etoposide d. Vincristine
53. All of the following anticancer agents cause bone marrow suppression EXCEPT a. Chlorambucil b. Daunorubicin c. Doxorubicin d. Flutamide (d)
54. All the following are hormonal agents used against breast cancer EXCEPT a. Letrozole
b. Exemestane c. Taxol
d. Tamoxifen (c)
55. Which is the most active single chemotherapeutic agent in the treatment of leiomyosarcoma? a. Adriamycin b. Daunorubicin c. Methotrexate d. Cisplatin (a) 56. Gemcitabine is effective in a. Head and neck cancers
b. Pancreatic cancer
c. Small-cell lung cancer d. Soft tissue sarcoma
57. All of the following statements about methotrexate are correct EXCEPT a. Folinic acid enhances the action of methotrexate
b. Methotrexate inhibits dihydrofolate reductase
c. Non-proliferative cells are resistant to methotrexate d. Methotrexate is used in the treatment of psoriasis
(a)
58. Mesna is given with cyclophosphamide to a. Increase absorption
b. Decreased excretion
c. Ameliorate hemorrhagic cystitis d. Decrease metabolism
59. A 35 yr old patient is having carcinoma lung with a past history of lung disease. Which of the following drugs should not be given?
a. Vinblastine b. Bleomycin c. Mithramycin d. Adriamycin
(b)
60. Arsenic is useful in the treatment of a. Acute promyelocytic leukemia
b. Myelodysplastic syndrome
c. Transient myeloproliferative disorder d. All of the above
61. Which of the following is an anti-metabolite? a. Methotrexate b. Cyclosporine c. Etoposide d. Vinblastine (a)
62. Mechanism of action of imatinib mesylate is a. Increase in metabolism of P glycoprotein
b. Blocking the action of P glycoprotein
c. Blocks the action of chimeric fusion protein of bcr abl d. Non-competitive inhibition of ATP binding site
63. Which of the following drugs is associated with untoward side effect of renal tubular damage? a. Cisplatin b. Streptozocin c. Methysergide d. Cyclophosphamide (a)
64. Which of the following chemotherapeutic agents is associated with secondary leukemia? a. Vinblastine b. Paclitaxel c. Cisplatin d. Bleomycin (c)
65. The drug imatinib acts by the inhibition of a. Tyrosine kinase b. Glutathione reductase c. Thymidylate synthetase d. Protein kinase (a)
66. The new drug pemetrexed useful in breast cancer belongs to which of the following category of the drugs?
a. Antitumor agent b. Alkylating agent c. Hormonal agent d. Antimetabolite
71. Sodium 2-mercapto ethane sulfonate is used as a protective agent in a. Radiotherapy b. Cancer chemotherapy c. Lithotripsy d. Hepatic encephalopathy (b) 72. Pulmonary fibrosis is a common complication after treatment with
a. 6-Mercaptopurine b. Vincristine
c. Bleomycin d. Adriamycin
73. A patient receiving allopurinol requires dose reduction of a. 6-Meracaptopurine b. Cyclophosphamide c. 6-Thioguanine d. Climetidine (a)
74. Which of the following are alkylating agents? a. Cyclophosphamide
b. Ifosfamide c. Methotrexate d. Vincristine
75. Anticancer drugs of plant origin is/are a. Vincristine b. Isotretinoin c. Bleomycin d. Methotrexate (a, b)
76. Alkylating agents are a. Vincristine b. Actinomycin-D c. Chlorambucil d. 5-Fluorouracil e. Cyclophosphamide (c, e)
77. Which of the following drugs are anticancer antibiotics? a. Vancomycin b. Actinomycin D c. Bleomycin d. Mithramycin e. Vincristine (b, c, d)
78. Metaphase arrest is caused by a. Griseofulvin b. Vincristine c. Paclitaxel d. Colchicine e. Etoposide (b, c, d)
79. The mechanism of anticancer action of fluorouracil is
a. Cross linking of double stranded DNA and the resulting inhibition of DNA replication and transcription
b. Cytotoxicity resulting from a metabolite that interferes with the production of dTMP c. Irreversible inhibition of dihydrofolic acid reductase
d. Selective action on DNA polymerase (b)
80. A cell cycle specific anticancer drug that acts mainly in the M phase of the cycle is a. Cisplatin
b. Etoposide c. Methotrexate d. Paclitaxel
81. Maintenance of high urinary pH is important during methotrexate treatment because
a. Bladder irritation is reduced
b. It decreases renal tubular secretion of methotrexate
c. Leucovorin toxicity is increased in a dehydrated patient d. Methotrexate is a weak acid
(d)
82. All of the following statements about methotrexate are true Except a. It is cell cycle specific and kills in the S phase
b. Its toxicity primarily affects bone marrow and epithelial structures c. Folic acid reverses its toxic effects
d. It is the drugs of choice for choriocarcinoma (c)
83. Mechanism of action of vincristine in the treatment of All is a. Inhibition of topoisomerase II to cause breaks in DNA strands b. Alkylation and cross linking DNA strands
c. Inhibition of DNA mediated RNA synthesis
d. Inhibition of polymerization of tubulin to form microtubules (d)
84. All of the following statements about vincristine are true EXCEPT a. It acts by inhibiting mitosis
b. Its prominent adverse effect is peripheral neuropathy c. It does not suppress bone marrow
d. It is a drug of choice for solid tumors (d)
85. All of following statements about are true about mercaptopurine EXCEPT a. It is metabolized by xanthine oxidase
b. It does not cause hyperuricemia
c. Its dose should be reduced when allopurinol is given concurrently d. It is an active metabolite of azathioprine
(b)
86. Which of the following immunosuppressants is not used for the treatment of cancers? a. Cyclophosphamide b. Cyclosporine c. Methotrexate d. 6-Mercaptopurine (b)
87. Which of the following drugs is not used in prostate carcinoma? a. Finasteride b. Diethylstilbesterol c. Testosterone d. Flutamide (c)
88. Pentostatin acts by inhibiting a. RNA dependent DNA polymerase b. Aldolase
c. Adenosine deaminase d. Adenylyl cyclase
89. Hand and foot syndrome is an adverse effect of a. 5-Fluorouracil b. Bleomycin c. Etoposide d. Actinomycin D (a)
90. Side effects of cisplatin include all of the following EXCEPT a. Nausea and vomiting
b. Nephrotoxicity c. Blindness
d. Ototoxicity (c)
91. Most common side effect of 5-fluoracil is a. G.I. toxicity
b. Bone marrow depression c. Cardiotoxicity d. Neurotoxicity (a) 92. Sterility is caused by a. Vinca alkaloids b. Alkylating agents c. Antimetabolites d.Actinomycin Ds (b)
99. Neoadjuvant chemotherapy is used in all except a. Esophageal carcinoma
b. Breast carcinoma c. Thyroid carcinoma
d. Non- small cell carcinoma of lung (c)
100.Which of the following anticancer drugs can cross blood brain barrier? a. Cisplatin
b. Nitrosourea c. Vincristine d. Vinblastine
101. Which of the following drugs produce significant nephrotoxicity? a. Cisplatin b. Carboplatin c. Vinblastine d. Vincristine (a)
102. Phocomelia is due to teratogenic effects of a. Thailidomide
b. Chlopromazine c. Methotrexate d. Carbamzepine
103. Folinic acid counteracts the toxicity of a. Doxorubicin b. Methotrexate c. Cyclophosphamide d. Fluorouracil (b)
104. Which of the following antineoplastic and immunosuppressant drugs is a dihydrofolate reductase inhibitor?
a. Methotrexate b. Adriamycin c. Vincristine
d. Cyclophosphamide (a)
105. Toxicity of nitrogen mustards can be decreased by a. Amifostine b. Folinic acid c. GM-CSF d. MESNA (c)
106. Which one of the following alkaloids is used as anticancer agent? a. Vincristine
b. Papaverine c. Ephedrine d. Atropine
107. The antimalignancy drug which is potentially cardiotoxic is a. Doxorubicin b. Bleomycin c. Fluorouracil d. Dacarbazine (a)
108. The drug of choice in choricarcinoma is a. Methotrexate
b. Actinomycin –D c. Vincristine
d. 6-thioguanine (a)
109. “Stocking and glove” neuropathy is seen in a. Vinblastine b. Paclitaxel c. Etoposide d. Mitroxantrone (b)
110Drug that is radioprotective is a. Paclitaxel
b. Vincristine c. Etoposide d. Amifostine
111. Hemorrhagic cystitis is caused by a. Cyclophosphamide b. Ifosfamide c. Vincristine d. Adriamycin (b)
112. Which of the following anti-cancer drug is cell cycle specific? a. Cyclophosphamide
b. Vincristine
c. Nitrogen mustard d. Doxourubicin
113. Which of the following anticancer drug is not ‘S’-phase specific? a. Methotrexate b. Meracaptopurine c. Ifosfamide d. Thiouanine (c)
114. All are alkylating agents except a. Cyclophosphamide
b. Lomustine c. Busulfan d. Zalcitabine
115. Chemotherapy is not useful in a. Chondrosarcoma b. Wilm’s tumor c. Choriocarcinoma d. All (a)
116. Cisplatin does not cause a. Cardiomyopathy
b. Nephrotoxicity c. Neuropathy d. Tinnitus
117. Cyclophosphamide can cause a. Hemorrhagic cystitis b. Cardiomyopathy c. Neuropathy d. Convulsions (a)
118. Which of the following is not an early adverse effect of methotrexate? a. Hepatic fibrosis
b. Myelosupression c. Nausea
d. Stomatitis (a)
119. Which of the following is not an antineoplastic antibiotic? a. Actinomycin D b. Doxorubicin c. Bleomycin d. Spiramycin (d)
120. All cause myelosuppression except a. Docetaxel vincristine
b. Vincristine c. Methotrexate d. Irrnotecan
121. Leucovorin rescue is related to a. Methotrexate toxicity b. Cyclophosphamide toxicity c. Oncovin toxicity d. Cisplatin toxicity (a) 122. Which of the following causes peripheral neuritis?
a. Methotrexete b. Vincristine c. Busulfan
d. Cyclophosphamide
123. The drug of choice for chronic myeloid leukemia, is a. Chlorambucil b. Busulfan c. Vincristine d. Procarbazine (b)
124. Proliferation independent agents include all the following except a. Vincristine
b. Carmustine c. Melphalan
d. Cyclophosphamide
125. People with high risk for development of breast cancer should be treated by prophylactic admini-stration of a. Tamoxifen b. Aminoglutethimide c. Diethyistibesterol d. Flutamide (a)
126. Which of the following is widely used in the management of carcinoma breast? a. Actinomycin D
b. Bleomycin c. Doxorubicin d. Dacarbazine
127. Rituximab is used in a. Hodgkin,s disease
b. Acute myeloid leukemia c. Non-Hodgkin lymphoma d. Multiple myeloma
(c)
128. Allopurinol potentiates action of a. Azathioprine
b. Busulfan c. Actinomycin d. Procarbazine
129. Alkylating agengts include
a. Doxorubicin
b. Cholorambucil
c. Vinblastine
d. Busulfan
e. Methotrexate
(b, d)
69. Sterile hemorrhagic cystitis is caused by a. Busulfan b. Ketoprofen c. Methicillin d. Cyclophosphamide (d)
70. A 50 year old woman, Hema has been diagnosed with locally advanced breast cancer and recommended for chemotherapy. She has five years history of myocardial infarction and congestive heart failure. Which antineoplastic drug should be best avoided?
a. Anthracycline b. Alkylating agent c. Platinum compound d. Bisphosphonates
67. Which of the following statements is FALSE regarding vincristine? a. It is an alkaloid
b. Its use is associated with neurotoxicity c. It does not cause alopecia
d. It is a useful drug for induction of remission in acute lymphoblastic leukemia (c)
68. A patient with cancer developed extreme degree of radiation toxicity. Further history revealed that the dose adjustment of a particular drug was missed during the course of radiotherapy. Which of the following drugs required a dose adjustment during
radiotherapy in order to prevent radiation toxicity? a. Vincristine
b. Dactinomycin
c. Cyclophosphamide d. 6- Mercaptopurine
37. Ifosfamide belongs to which group of anticancer drugs? a. Alkylating agents b. Antimetabolites c. Mitotic inhibitors d. Topoisomerase inhibitors (a)
38. A 56 year old female presented with breast carcinoma and she was prescribed herceptin (trastuzumab). Which of the following statements regarding this drug is true?
a. It is an antibody produced entirely from mouse con taining no human component. b. It is a monoclonal antibody produced by injecting her-2 antigen
c. It is a polyclonal antibody
d. It is a monoclonal antibody containing only human component (b)
93. Which of the following is a common side effect of cisplatin a. Diarrhea b. Vomiting c. Pulmonary fibrosis d. Alopecia (b)
94. The antimetabolite ‘X’ inhibits DNA polymerse and is one of the most active drugs in the treatment of leukemia. Although myelo-suppression is done limiting, the drug may also cause cerebellar dysfunction, including ataxia and dysarthria. Which of the following can be ‘X’? a. Bleomycin b. Cytarabine c. Mercaptopurine d. Methotrexate (b)
95. Which of the following antineoplastic drugs should not be administered to a chronic alcoholic patient due to risk of development of disulfiram like reaction?
a. Dacarbazine b. Procarbazine c. Melphalan d. Hydroxyurea
(b)
96 Roopa devi, a 65 year old female with overian cancer is being treated with cisplatin based chemotherapy. All of the following are used to limit the toxicity of cisplatin except
a. N-acetylcysteine b. Slow rate of infusion c. Chloride dieresis d. Amifostine
97. Roopmati, A 56 year old femal with lymph node positive breast cancer was treated with systemic chemotherapy. Four weeks later, she developed frequent urination, suprapublic pain, dysuria and hematuria. Which of the following could have prevented this patient’s condition?
a. Folinic acid b. Mesna c. Dexazoxane d. Amifostine
(b)
98. Sunder, a ypung male was diagnosed as suffering from acute myeloid leukemia. He was started on induction chemotherapy with doxorubicin based regiments. Induction regimen was successful. Two months later, he presents to opd with swelling of both the feet and breathlessness on climbing the stairs. He also complains the he had to wake up many times because of breathlessness. Which of the following is most likely responsible for this patient’s symptoms?
a. Restrictive cardiomyopathy b. Hypertrophic cardiomyopathy c. Dilated cardiomyopathy
d. Pericardial fibrosis (c)