about cancer and its treatment and recent advances in cancer treatment.

1. ANTINEOPLASTIC AGENTS &
RECENT DRUGS USED IN
CANCER.
Presented by : Adhira Ambala
H.T No: 13TK1R0001
B.Pharmacy 4th year
Guided by: Mrs.Suhasini (Asst.proff.)
SVS School of pharmacy

2. Contents
1. Introduction.
2. What is cancer?
3. Types of cancer.
4. Causes and risk factors.
5. The classification of anticancer drugs.
6. Recently approved drugs.
7. References.

3. Introduction
• Cancer is not a single disease . It is a group of more
than 200 different diseases.
• Cancer may spread to other parts of the body.
• Currently 1 in 4 deaths in USA are due to cancer.
• 1 in 17 deaths are due to lung cancer.
• An estimated 2,22,520 people diagnosed lung
cancer in the united states in 2010.

4. INDIA.
• The four most common cancer in India are
• Male-oropharynx, esophagus, stomach and lower
respiratory tract
• Female-breast, cervix, oropharynx and esophagus
• Tobacco is widely used in India
• 91% cases of oropharynx is due to Tobacco use
• 60% cases in female are breast, cervix and ovary
cancer

5. WHAT IS CANCER?
• Antineoplastic agents are drugs used for the
treatment of cancer.
• Cancer or neoplasm ( Greek neo = new); plasm =
formation ) refers to a group of disease caused by
several agents viz.
• Chemical compounds, radiant energy .
• Cancer is characterised by an abnormal and
uncontroled division of cells exhibiting varying,
Degrees of malignancy which produce tumors and
invade adjacent normal tissue.

6. • Often cancer cells separate themselves from
primary tumor and carried by the lymphatic
system , reach distant sites of the organism ,
where they divide and form second
tumors(metastasis).
• The main characteristics of malignant are,
therefore, (a) autonomous growth , insentive to
the normal control mechanisms that limits cell
growth and division in differentiated tissues and
(b) invasiveness of adjacent capillaries and lymph
channel.

7. TYPES OF CANCER
Types of Cancer AFFECTED AREA
ANAL CANCER ANUS
BREAST CANCER BREAST
BLADDER CANCER URINARY BLADDER
BONE MARROW CANCER SHAFTS OF LONG BONES
COLON CANCER COLON
CERVICAL CANCER CERVIX
EYE CANCER EYE
GYNAEOCOLOGICAL CANCER FEMALE REPRODUCTIVE ORGANS
LUNG CANCER LUNGS
OSTEO SARCOMA METAPHYSEAL REGION OF LONG BONES
WILMS TUMOUR KIDNEY
LEUKEMIA BLOOD
LARYNX CANCER LARYNX
TESTICULAR CANCER TESTIS
RECTAL CANCER RECTUM

8. CAUSES AND RISK FACTORS
1.Environment
• cigarette smoke
 chemicals
 UV light
 viruses
2.Metabolic processes
• free radicals
 DNA copying and
repair defects
3.Inherited genetic mutations

10. The Classification of Anticancer Drugs
A. Drugs acting directly on cells (Cytotoxic
drugs)
1. Alkylating agents:
o These compounds produce highly reactive
carbonium ion intermediates which transfer
alkyl groups to cellular macro molecules by
forming covalent bonds.
o Alkylation results in cross linking/ abnormal
base pairing/scission of DNA strand.

11. Mechanism of action

12. Nitrogen mustard
Breast cancer,
Multiple
myeloma
head and neck carcinomas,
osteogenic sarcoma
Hodgkin’s disease,
T-cell lymphoma
Chronic lymphocytic
leukemia
Multiple myeloma,
Ovarian cancer, Breast
cancer

13. CYCLOPHOSPHAMIDE
SAR:
1. BIS-2-
CHLOROETHYLAMINO
GROUP IS ESSENTIAL.
2. CHLORO ATOM
PROVIDES MAXIMUM
ACTIVITY.
3. LEVO-ISOMER IS
INACTIVE.
USES:
1. Multiple myeloma, chronic lymphocytic
leukemia, Hodgkin's disease, ovarian and lung
cancer.
ADVERSE REACTIONS:
HAIR LOSS, STERILITY, TESTICULAR
ATROPHY, OVARIAN FIBROSIS,
SUPPRESSION OF MENSTRUATION.

14. Bestrabucil (phase I trial)
[Chlorambucil derivative]
Bendamustine
Recent drugs based on Nitrogen
mustard
Uramustine (Nitrogen mustard+Uracil
Derivative)

15. Ethylenimine
Alkyl sulfonate
Ovarian cancer, Breast cancer
Lymphoma
Chronic Myeloid
Leukemia

16. Nitrosoureas
Triazine
:- meningeal leukaemias and brain tumours(can cross
BBB)
Malignant melanoma;
Hodgkin's disease.

17. 2. Antimetabolites
o These are analogues related to normal
components of DNA or of coenzymes involved in
nucleic acid synthesis.
o They competitively inhibit utilization of the
normal substrate or get themselves incorporated
forming dysfunctional macromolecules.
o Several of the useful drugs used in
antimetabolite therapy are purines, pyrimidines,
folates, and related compounds.

18. Folate antagonist:
Methotrexate
(NEOTREXATE)
MECHANISM OF ACTION:
•Methotrexate acts an antifolate by binding almost irreversibly to
the enzyme dihydrofolate reductase.
•Which prevents the formation of the coenzyme tetrahydrofolic
acid, essential for replication of animal cells.
USES:
Choriocarcinoma, trophoblast tumor and immunosuppressive agents.
Adverse effects:
Megaloblastic anemia, leukemia, diarrhoea, alopecia, intestinal tumour.

19. Purine antagonist
o These are highly effective antineoplastic drugs.
oThey are converted in the body to the
corresponding monoribonucleotides which inhibit
the conversion of inosine monophosphate to
adenine and guanine nucleotides.
N
N
N
H
N
SH
6-mercaptopurine
N
N
N
H
N
SH
H2N
Thioguanine
USE: Childhood acute leukemia
USE: Adult acute leukemia

20. • Recent drugs based on purines and related
compounds:
N
N
N
N
NH2
Cl
O
HO
HO
Cladribine
N
N
N
N
NH2
O
HO
HO
Vidarabine
OH
N
N
N
N
NH2
O
HO
HO
Clofarabine
F
Cl
N
N
O
HO
HO
Pentostatin
HN
N
OH
N
N
N
N
NH2
O
HO
O
OH
PHO
O
OH F
Fludarabine

21. Pyrimidine antagonist
o Pyrimidine analogues have varied applications
as antineoplastic, antifungal and antipsoriatic
agents.
HN
N
H
O
O
F
5-Fluorouracil
5-Fluorouracil is converted in the
body to the corresponding
nucleotide 5-fluoro-2-deoxyuridine
monophosphate, which inhibits
thymidylate synthase and blocks the
conversion of deoxyuridilic acid to
deoxythymidylic acid.
This leads to elective failure of DNA
synthesis.
Adenocarcinoma,
Skin cancer
Mechanismof action:

22. Recent drugs

23. 3. Natural anticancer agents:
Vinca alkaloids
o These are mitotic inhibitors, bind to
microtubular protein-'tubulin', prevent its
polymerization and assembly of microtubules,
cause disruption of mitotic spindle and interfere
with cytoskeletal function.
o The chromosomes fail to move apart during
mitosis: metaphase arrest occurs.
o They are cell cycle specific and act in the
mitotic phase.

24. Hodgkin’s disease,
Acute lymphocytic
leukemia,
Lung cancer

25. VINCRISTINE
MECHANISM OF ACTION: USES:
•Acute leukemia,
•lymphomas, wilm’s
tumour, choriocarcinoma.
ADVERSE REACTION:
•Neurotoxicity, areflexia,
paralytic ileus.

26. Taxanes
o First isolated from bark of
Western / Pacific yew (Taxus
brevifolia)
Uses: It is used for treatment
of lung, ovarian and breast
cancer.
Mechanism of action: Taxanes hyper-stabilizes
microtubule structure (freez them). Taxanes binds to
the β subunit of tubulin ,the resulting microtubule/
Taxanes complex does not have the ability to
disassemble. This adversely affects cell function
because the shortening and lengthening of
microtubules is necessary for their function.

27. Semi-synthetic derivatives
Ovarian cancer, Breast cancer,
Non –small cell lung cancer

28. Epipodophyllotoxin
From Podophyllum peltarum
May apple
O
O
O
OMe
OMeMeO
OH
O
Podophyllotoxin
O
O
O
OH
OMeMeO
O
Etoposide
O
OO
HO
HO
MOA: Affects DNA
topoisomerase II
(not intercalating)
DNA strand
breakage
Uses:Small cell lung cancer, Non-Hodgkin’s
lymphomas,
Kaposi’s sarcoma, Cervical cancer

29. Camptothecin analogues
o First isolated Camptotheca acuminata
(Chinese tree).
o Inhibits DNA topoisomerase II DNA
strand breakage
N
N
O
O
OOH
Camptothecin,
toxic, Lead comp.
N
N
O
O
OOH
HO
N
N
N
O
O
OOH
O
N O
N
Topotecan
Hycamtin®
Irinotecan
Campto®
Semisynthetic
USES: Ovarian cancer, Small cell lung cancer

30. 4. Antibiotics
o These are products obtained from
microorganisms and have prominent antitumour
activity.
o Practically all of them intercalate between DNA
strands and interfere with its template function.

31. Actinomycin D
Wilms' tumour,
Rhabdomyosarcoma
Adverse reaction:
-bone marrow suppression
-sensitizes to radiation, and inflammation at
the sites of prior radiation therapy may occur.
-gastrointestinal adverse effects.
Examples:

32. Doxorubicin
Mitoxantrone
Kaposi’s sarcoma,
Small cell lung cancer,
Breast cancer,
Malignant lymphomas
Prostate cancer,
Multiple sclerosis

33. Mitomycin
Daunorubicin
Kaposi’s sarcoma,
Acute myeloid leukemia
Carcinomas of the cervix,
Breast, lung, stomach

34. Recent anticancer antibiotics drugs:
Calicheamicin
(Preclinical )

35. o 5. Miscellaneous :
o These drugs have been developed by
random synthesis and testing for anti tumour
activity.
Procarbazine
Hydroxyurea
Hodgkin's disease,
Non-Hodgkin lymphomas,
Oat cell carcinoma of lung
Chronic myeloid leukaemia,
Psoriasis, Polycythaemia

36. Cisplatin
Carboplatin
Imatinib
Metastatic testicular
and
Ovarian carcinoma
Squamous carcinoma of
head
and neck,
Small cell lung cancer,
Seminoma
chronic myeloid
leukaemia

37. Recent drugs
Gefitinib
Erlotinib
Crizotinib
Non-Small
Cell lung
cancer
(PROTEIN
KINASE
INHIBITORS)
Oxaliplatin
Ovarian carcinoma,
Seminoma

38. B. Drugs acting on Hormones
o It involves the manipulation of the endocrine
system through exogenous administration of
specific hormones, particularly steroid hormones,
or drugs which inhibit the production or activity of
such hormones.
o Because steroid hormones are powerful drivers
of gene expression in certain cancer cells,
changing the levels or activity of certain hormones
can cause certain cancers to cease growing, or
even undergo cell death.

39. 1. Corticosteroids :
o Corticosteroids are strong anti-inflammatory
drugs.
Examples
Prednisolone
palliation of lymphomas
and leukemias

40. 2. Estrogens
o The agonist is occasionally used to treat
prostate cancer through suppression of
testosterone production.
Fosfestrol
carcinoma
prostate
Ethinylestradiol

41. 3. ESTROGEN INHIBITORS
TamoxifenToremifene
o Acts by selective antagonism of the estrogen
receptor.
Breast
cancer

42. 4.Aromatase inhibitors
• Aromatase is the enzyme that synthesizes estrogen.
• Aromatase inhibitors (AIs) are a class of drugs used in
the treatment of breast cancer and ovarian cancer in
postmenopausal women.
Breast cancer
Letrozole

43. 5. Antiandrogen
•prevent androgens from expressing their biological
effects on responsive tissues.
•Antiandrogens alter the androgen pathway by blocking
the appropriate receptors, competing for binding sites on
the cell's surface, or affecting androgen production.
USES: Antiandrogens are most frequently used to treat
prostate cancer.
Flutamide
Nilutamide

44. Recently Approved Drugs by FDA
DRUGS USES
2016
ofatumumab Chronic lymphocytic
leukemuia
eribulin Unsectable or metastatic
liposarcoma
olaratumab Soft tissue sarcoma
crizotinib Non- small cell lung cancer
defitelio Adult and pediatric with
hepatic venoocculsive
disease(VOD)
cabozantinib Renal cell carcinoma

45. DRUGS USES
2015
Palbociclib postmenopausal, advanced
breast cancer
levnatunib Thyroid cancer
panobinostat Multiple myeloma
nivolumab Non-small cell lung cancer
dinutuximab Pediatric patients with high risk
neuroblastoma
ramucirumab Metastatic colorectal cancer
irinotecan Metastatic adrenocarcinoma

46. Drugs Uses
2014
Belinostat Peripheral T-cell lymphoma
Ramucirumab Gastric cancer
Ibrutinib Chronic lymphocytic leukemia
Idelalisib Relapsed Chronic lymphocytic leukemia
Ceritinib Non-small cell lung Cancer
lanreotide Metastatic gastroenteropancreatic tumours

47. Drugs Uses
2013
Obinutuzumab Chronic lymphocytic leukemia
Afatinib Metastatic non-small cell lung cancer
Ibrutinib Mantle cell lymphoma
Trametinib Metastatic melanoma
Pomalidomide Relapsed and refractory multiple myeloma
Lenalidomide Mantle cell lymphoma
Regorafenib Gastrointestinal stromal tumor
Dabrafenib Metastatic melanoma
Denosumab Prostate cancer

48. References
2. Essentials of Medical Pharmacology, Sixth Edition, K.D TRIPATHI
1. Wilson and Gisvold's textbook of organic medicinal and
pharmaceutical chemistry, Twelfth Edition, Charles Owens
wilson, Ole Gisvold
3. Foye’s Principles of medicinal chemistry, Sixth Edition,
http://www.fda.gov/drugs/informationondrugs/approveddrug
s/ ucm279174.htm
4.