Classification of anti cancer drugs

1. DR.INDU SASIKUMAR
CLASSIFICATION OF
ANTI CANCER DRUGS

2. • Mustard gas : chemical warfare agent during World
War : 1943 !!
• Explosion at Bar Harbour .
• Autopsies : profound lymphoid and myeloid
suppression
• Goodman and Gilman : Treat lymphoma .
• In collaboration with a thoracic surgeon, Gustaf
Lindskog, they injected mustine into a patient with
Non-Hodgkin's lymphoma.
Dramatic reduction in the patient's tumor masses.

3. The Classification of Anticancer Drugs
According to the cycle or phase specificity of the
drug
According to biochemical mechanism of anticancer
action
According to chemical structure

4. G1 – Pre synthesis
(nucleic acid )

5. According to the cycle or phase specificity of
the drug:
cell cycle nonspecific agents (CCNSA)
cell cycle specific agents (CCSA)

6. CCNSA：drugs that are active throughout the cell cycle.
CCSA : drugs that act during a specific phase of the cell cycle.

7. CELL CYCLE SPECIFIC AGENTS
•Kills only actively dividing cells
•Useful in short course / pulse treatment
•CCS drugs are generally scheduled after CCNS drugs to improve cell
kill
•They are generally effective in hematological malignancies and solid
tumours with large growth fraction .

8. Cell Cycle Specific Agents (CCSA)
G1 phase Specific drug :
L asparaginase
S Phase Specific Drug:
Antimetabolites, Topoisomerase II Inhibitors
M Phase Specific Drug:
Vinca Alkaloids, Taxanes
G2 Phase Specific Drug:
Bleomycin , Topoisomerase I blocker

9. Cell Cycle Nonspecific Agents (CCNSA)
Drugs that are active throughout the cell cycle
 Alkylating Agents
 Platinum Compounds
 Anti tumour antibiotics

11. According to Mechanism of action …
Block nucleic acid (DNA, RNA) biosynthesisBlock
Inhibit DNA replicationInhibit
Interfere transcription and block RNA synthesisInterfere
Interfere protein synthesis and function
Influence hormone homeostasisInfluence
Interfere

12. Block Nucleic Acid (DNA, RNA) Biosynthesis
Antimetabolites:
Folic Acid Antagonist: inhibit dihydrofolate
reductase (methotrexate)
Pyrimidine Antagonist: inhibit thymidylate
synthetase (fluorouracil)
Purine Antagonist: inhibit interconversion of purine
nucleotide (mercaptopurine)

13. Influence the Structure and
Function of DNA
Alkylating Agent: mechlorethamine, cyclophosphamide
Platinum: Cisplatin
Antitumour Antibiotic: bleomycin and mitomycin C
Topoisomerase inhibitor: camptothecine and
podophyllotoxin

14. Interfere Transcription and
Block RNA Synthesis
They intercalate with DNA strands and interfere with
template function to block RNA production.
Anticancer antibiotics

15. Interfere Protein Synthesis
Antitubulin: vinca alkaloids and taxanes;
Influence amino acid supply: L-asparaginase

16. Influence Hormone Homeostasis
Hormonal Drugs which bind to hormone receptors to
block the actions of the sex hormones which results
in inhibition of tumor growth.

17. According to Chemical Structure !

18. ANTIMETABOLITESALKYLATING
AGENTS
MICROTUBULE
INHIBITORS
ANTICANCER
ANTIBIOTICS
HORMONAL
AGENTS
TOPOISOMERASE
INHIBITORS

20. Platinum based alkylating agents Cisplatin
Carboplatin
Oxaliplatin

21. Cell cycle non specific agent
Act on both resting as well as dividing cells

24. CYCLOPHOSPHAMIDE
ALDOPHOSHAMIDE
PHOSPHPORAMIDE
MUSTARD
ACROLEIN
(TOXIC METABOLITE)

26. Triazine : Temozolamide Anaplastic astrocytoma
Glioblastoma
Metastatic melanoma
Methylhydrazine:Procarbazine Hodgkins and Non hodgkins
Brain tumors
Cutaneous T cell lymphoma

27. Toxicities of Alkylating agents
Gastrointestinal distress
Bone marrow suppression
Alopecia
Secondary cancers
Sterility

29. Platinum
agents !
Cisplatin
OxaliplatinCarboplatin

30. MECHANISM OF ACTION
Platinum based alkylating agents

31. Indication of cisplatin
• Head and neck cancer with 5 flurouracil
• Non small cell lung cancer: as part of cisplatin/etoposide or cisplatin/gemcitabine
regimen.
• Ovarian cancer: cisplatin/paclitaxel regimen or cisplatin/cyclophosphamide regimen.
• Testicular cancer: BEP regimen
• Locally advanced Ca esophagous
• Cisplatin act as radiosensitising agent

32. ADVERSE EFFECTS OF CISPLATIN

33. Indication of carboplatin
1.Ovarian cancer.
2. Germ cell tumors.
3. Head and neck cancer.
4. Small cell and non–small cell lung cancer.
5. Bladder cancer.
6. Relapsed and refractory acute leukemia.
7. Endometrial cancer.

34. Carboplatin
MYELOSUPRESSION
Dose limiting toxicity : Thrombocytopenia > leucopenia

35. AUC
DOSE: Calculated to a target area under curve based on GFR.
Calvert formula : dose in mg= target AUC X (GFR+25)
GFR:
Target AUC is usually b/w 5 and 7mg/ml/min for previously untreated patients.In previously
treated patients,lower AUC b/w 4 and 6mg/ml/min are recomended

36. Indications of
oxaliplatin
1.Metastatic colorectal cancer—FDA-
approved in combination with infusional
5-FU/LV in patients with advanced,
metastatic disease.
2. Early-stage colon cancer—FDA-
approved as adjuvant therapy in
combination with infusional 5-FU/LV in
patients with stage III colon cancer
3. Metastatic pancreatic cancer.
4. Metastatic gastric cancer and
gastroesophageal cancer.

37. Oxaliplatin
Dose limiting -neurotoxicity.
 Avoid exposure to cold following drug administration ,which can trigger or
worsen acute neurotoxicity.
Neurotoxicity-
Acute toxicity (80% to 85%) : peripheral sensory neuropathy with distal
paresthesia and voice changes.
Chronic toxicity is dose dependent- proprioception and neurosensory function.
Reversible :returns to normal within 3 to 4months of discontinuation of
oxaliplatin.

38. +

39. Resistance of Alkylating Agents
Membrane transport may
be decreased.
The drug may be bound by
glutathione (GSH) via GSH-
S-transferase or
metallothioneins in the
cytoplasm and inactivated.
The drug may be
metabolized to inactive
forms.

40. ANTIMETABOLITES
S phase-specific drugs that are structural analogues related
to normal components of DNA or of coenzymes involved in
nucleic acid synthesis.
They competitively inhibit utilization of normal substrate or
get themselves incorporated forming dysfunctional
macromolecules .
Immunosuppressive properties
Myelosuppression is the dose-limiting toxicity for all drugs in
this class.

42. Mtx ..
The structures of MTX and folic acid are similar.
Inhibits dihydrofolate reductase, the enzyme that normally converts dietary
folate to the tetrahydrofolate . THFA is required for one carbon reactions in
denovo purine synthesis and aminoacid interconversion reactions
Indication
Choriocarcinoma
Acute lymphocytic leukemia
Head and neck tumours

43. Adverse Effects：
Myelosuppression
Low doses : Megaloblastic
anemia
High doses : Pancytopenia
Severe gastrointestinal
disturbances.
Renal toxicity may
occur because of
precipitation
(crystalluria) of the 7-
OH metabolite of MTX.

44. Purine analogue : 6-Mercapapurine（6-MP)

45. 6-Mercapapurine（6-MP）
Indications:
Mercaptopurine is used primarily for the maintenance of remission in patients with
acute lymphoblastic leukemia (with MTX )
Induction therapy: 2.5 mg/kg PO daily…... Maintenance therapy: 1.5–2.5 mg/kg PO
daily.
Adverse Effects:
Well tolerated
Myelosuppression
Hepatotoxicity.

46. Pyrimidine analogue
5-Fluorouracil (5-FU)

47. 5-Fluorouracil (5-FU)
1.Colorectal cancer—Adjuvant setting and advanced disease
2. Breast cancer—Adjuvant setting and advanced disease
3. GI malignancies, including anal, esophageal, gastric, and pancreatic
cancer
4. Head and neck cancer
5. Ovarian cancer
7. Topical use in basal cell cancer of skin and actinic keratoses

48. - Cardiotoxicity
- Diarrhea

51. Anti Microtubule Agents
VINCA
ALKALOIDS
TAXANES

52. MICROTUBULES TUBULIN SPINDLE
VINCA ALKALOIDS
TAXANES

54. VINCA ALKALOIDS
prevent microtubule
assembly
TAXANES
Prevent microtubule
disassembly

56. VINCA ALKALOIDS
VINCRISTINE Leukemias
Lymphomas
Neuroblastoma
Multiple myeloma
Neuropathy
Paralytic ileus
VINBLASTINE Lymphoma
Germ cell tumours
Myelosuppression

57. TAXANES
Paclitaxel Ovarian cancers
Breast cancer
Lung cancer
Myelosupression
Neurotoxicity
Hypersensitivity reaction
Docetaxel Locally advanced Breast
cancer & Lung cancer
Metastatic Prostate
Cancer
Locally advanced head
and neck cancer
Neutropenia
Diarrhoea
Hypersensitivity reaction
Fluid retension
USES ADVERSE EFFECTS

58. Chemotherapy extravasation

59. Topoisomerase inhibitors

60. Topoisomerase Inhibitors
•Topoisomerases are enzymes that participate in the overwinding or underwinding
of DNA.
•During DNA replication and transcription, DNA becomes overwound ahead of a
replication fork.
•This torsion would eventually stop the ability of DNA or RNA polymerases involved
in these processes to continue down the DNA strand.
•In order to prevent and correct these types of topological problems caused by the
double helix, topoisomerases bind to DNA and cut the phosphate backbone of
either one or both the DNA strands.
•This intermediate break allows the DNA to be untangled or unwound, and, at the
end of these processes, the DNA backbone is resealed again.

62. Topoisomerase inhibitors are often divided according to
which type of enzyme it inhibits:
Topoisomerase I inhibitors:
CAMPTOTHECIN ANALOGUES : Irinotecan, Topotecan, Camptothecin
Topoisomerase II inhibitors:
EPIPODOPHYLLOTOXIN : Etoposide , Teniposide

63. Irinotecan
Drug class: Topoisomerase I inhibitor.
Mechanism of action:
Its active metabolite binds to and stabilizes the
topoisomerase I-DNA complex, inducing DNA single-strand
and double-strand breaks, preventing DNA repair, thereby
leading to cellular death.
Indications: Metastatic colorectal cancer.
Toxicities:
Diarrhea
 Myelosuppression
Cholinergic symptoms

64. Etoposide
Drug class: topoisomerase II inhibitor.
Mechanism of action: Etoposide is a semisynthetic
derivative of podophyllotoxin that inhibits topoisomerase
II by stabilizing the topoisomerase II-DNA complex,
thereby preventing DNA unwinding. This results in
inhibition of DNA synthesis.
It is cell cycle-specific with maximum effect in the S and
G2 phases.
Indications: Germ cell tumors and small cell lung cancer
Toxicities:
Myelosuppression : Neutropenia
Hypersensitivity reactions
Radiation recall

65. RADIATION RECALL
Bleomycin
Dactinomycin
Daunorubicin
Docetaxel
Doxorubicin
Etoposide
5 FU
Melphalan
Methotrexate

66. ANTICANCER ANTIBIOTICS
Bleomycin
Actinomycin D
Anthracycline Antibiotics: daunorubicin, doxorubicin ,
epirubicin , idarubicin
Mitomycin C

67. Indication Adverse effect

68. Mitomycin C:
Mitomycin C is an
antineoplastic antibiotic
that alkylates DNA and
thereby causes strand
breakage and inhibition of
DNA synthesis.
Metastatic gastric cancer
Metastatic pancreatic
cancer
Myelosuppression
Nausea / Vomiting
CHF
Vesicant

69. • Glucocorticoids : Prednisolone
• Oestrogen : Ethinylestradiol , fosfestrol
• Selective estrogen receptor modulator : Tamoxifen
• Selective estrogen receptor downregulator:
Fulvestrant
• Aromatase inhibitors : Letrozole , anastrozole
• Antiandrogen : Flutamide
• GnRH analogue : Nafarelin , triotorelin
• Progestins : Hydroxyprogestrone acetate.
HORMONAL
DRUGS

70. Glucocorticoids : Prednisolone Primarily used in childhood leukemia
and lymphoma
Osteoporesis
Hypertension
Hyperglycemia
Weight gain
Estrogen : Ethinylestradiol ,
Fosfestrol
Symptomatic relief in carcinoma
prostate which is an androgen
dependent tumour
Cardiac and cerebrovascular
complications
Carcinoma male breast
SERM : Tamoxifen • Non steroidal : Estrogen
antagonist
• ER + Breast Cancer
Thromboembolism
Hot flashes
Menstural irregularities
Risk of endometrial cancer
SERD: Fulvestrant • Estrogen receptor antagonist
• Hormone + Ca Breast in
postmenopausal with disease
progression with antiestrogen
Hepatic impairment
Peripheral edema
USES ADVERSE EFFECTS

71. Uses Adverse effects
Aromatase inhibitors :
letrozole , anastrozole
Hormone + Breast cancer :
adjuvant or metastatic
disease
Osteoporesis
Antiandrogen : Flutamide ,
Bicalutamide
Advanced and metastatic
disease : Ca Prostate
Impotence ,loss of libido ,
gynecomastia
GnRH analogues : Nafarelin ,
Tritorelin
Indirectly inhibits estrogen
/androgen secretion by
suppressing FSH and LH
release from pituitary and
has a palliative effect in
advanced estrogen /
androgen dependent ca –
:breast and prostate

73. THANKYOU ……