Anticancer drugs with pharmacology

2. Cancer (Malignant
neoplasm) is a class
of diseases in which
a group of cells
display uncontrolled
growth, invasion,
and sometimes
metastasis

3. WW (I) exposure to mustard gas
led to the observation that
alkylating agents caused marrow
and lymphoid hypoplasia which
was further studied during
WW(II)
This observation led to the
direct application of such agents
to patients with Hodgkin’s
disease and lymphocytic
lymphomas.
The origin of cancer chemotherapy

4. 1948, SydneyFarber successfullyused Antifolates to induce remission inchildrenwith ALL.
1958, Roy Hertz demonstrated Methotrexateas a singlebest agent for choriocarcinoma,
1959, FDA approved the alkylating agent, Cyclophosphamide

6. Classification -
A. Alkylating agents
1. Nitrogen mustards – Mechlorethamine (Mustine HCL), Cyclophosphamide,
Ifosfamide, Melphalan, Chlorambucil
2. Ethylenimine - Thio-TEPA, hexamethylmelamine (Altretamine)
3. Alkyl sulfonate – Busulfan
4. Nitrosoureas – Carmustine, Lomustine, Streptozocin
5. Triazines - Procarbazine, Dacarbazine, Temozolomide

7. A B C
Nitrogen mustards
Multiple myeloma
Wilms tumor
S/E SIADH
CARDIOTOXIC
HEMORRHAGHIC CYSTITIS-
CAUSED BY ACROLINE RX
MESNA ,NACYL CYSTINE
MYELOSUPRESSION
Multiple myeloma CLL

8. A B C
Alkyl sulfonate
CML

9. A B C
Ethylenimine

10. A B C
Nitrosoureas(BBB PENETRATION)
MALIGNENT MELANOMA SAMLL CELL LUNG
CARCINOMA
MALIGNENT
INSULINIMA/CARCINOID
NITROSUREA RESISTANT BRAIN TUMOR RX-TEMOZOLAMIDE

11. A B C
Triazines
SOFT TISSUE SARCOMAS

12. 2. Platinum coordination complexes –
Cisplatin, Carboplatin,Oxaliplatin
3. Antimetabolites –
Pyrimidine analogs – 5-Fluorouracil , Cytarabine
(cytosine arabinoside), Capecitabine, Gemcitabine
Purine analogs – 6-Mercaptopurine, 6-Thioguanine,
Azathioprine, Fludarabine, Cladribine, Pentostatin
Folic acid antagonist – Methotrexate, Pemetrexed

13. Platinum complexes
GIVEN IV ALWAYS

14. Purine analogs

15. Pyrimidine analogs
A wonderful serenity has taken possession of my entire soul,
like these sweet wonderful serenity mornings
A wonderful serenity has taken possession of my entire soul,
like these sweet wonderful serenity mornings

16. Folic acid antagonist
A wonderful serenity has taken possession of my entire soul,
like these sweet wonderful serenity mornings

17. 4. Microtubule damaging agents – Vincristine(
Oncovin), Vinblastine, Vinorelbine, Paclitaxel,
Docitaxel, Estramustine
5. Topoisomerase-2 inhibitors – Etoposide,Teniposide
6.Topoisomerase-1 inhibitors- Topotecan, Irinotecan
7.Antibiotics – Actinomycin D (Dactinomycin),
Doxorubicin, Daunorubicin(Rubidomycin), Epiburicin,
Mitoxantrone,Bleomycins, Mitomycin C

18. 8.Miscellaneous – Hydroxyurea, L-Asparaginase,
Tretinoin, Arsenic trioxide
B. Targeted Drugs –
1.Tyrosine Protein Kinase Inhibitors – Imatinib, nilotinib
2. EGF receptor inhibitors – Geftinib,
Erlotinib,Cetuximab
3. Angiogenesis Inhibitors – Bevacizumab, Sunitinib
4. Proteasome Inhibitor – Bortezomib
5. Unarmed monoclonal antibody – Rituximab,
Trastuzumab

19. C. Hormonal drugs –
1. Glucocorticoids – Prednisolone and others
2. Estrogens – Fosfestrol, Ethinylestradiol
3. Selective estrogen receptor modulators-
Tamoxifen,Toremifene
4. Selective estrogen receptor down regulators –
Fulvestrant
5. Aromatase Inhibitors – Letrozole, Anastrozole ,
Exemestane
6. Antiandrogens – Flutamide,Bicalutamide
7. 5-α reductase Inhibitors – Finasteride, Dutasteride
8. GnRH analogues – Nafarelin,Leuprorelin,triptorelin
9. GnRH antagonists – Cetorelix, Ganirelix, Abarelix
10. Progestins – Hydroxyprogesterone acetate, etc.

20. 20
Daughter
Cells
DNA Copied
Cells
Mature
Cells prepare for Division
Cell Divides into Identical cells
Phases of cell cycle

23. The Log-Kill hypothesis -
 The CELL KILL HYPOTHESIS proposes that actions of CCS drugs
follow first order kinetics: a given dose kills a constant
PROPORTION of a tumor cell population (rather than a
constant NUMBER of cells).

24. POMP(Methotrexate,Vincristine,6MP,Prednisolone)regimen was able to induce long term remission in children with ALL
MOPP(Nitrogen Mustard,Vincristine,Procarbazine,Prednisolone
successfully cured HL and NHL
CHOP(cyclophosphamide doxorubicin, vincristine, Prednisolone)
successfully cured diffuse large B cell lymphoma
ABVD(doxorubicin,bleomycin,vinblastine,dacarbazine)
successfully cured diffuse large B cell lymphoma
CMF (CYCLOPHOSPAMIDE+METHOTREXATE+5FU) BREAST CARCINOMA