Antineoplastic Drugs

Description of neoplasm & anti neoplastic drugs.

2. A=Anticancer drugs cause
N=Nausea and vomiting
T=Treatment regimen must be followed
I=Individualized dosage
N=New drugs appear on the market
E=Exposure time kept to a minimum
O=Only a physician can administer
P=Protect yourself
L=Look, listen, and learn
A=Assessment of laboratory tests
S=Safe dosage based on weight
T=Toxicities
I=Inform patients
C=Classification of agents

3. Neoplasm 
It is an abnormal mass of tissue as a result of Neoplasia
(Neoplasia (new growth in Greek) is the abnormal proliferation of cells)
Classification of Neoplasm
Benign
Potentially malignant
Malignant 

4. Warning Signs of
Neoplasm
Changes in bowel or bladder habits
A sore that will not heal
Unusual bleeding, discharge
Thickening or lump in breast or elsewhere
Indigestion, difficulty swallowing
Obvious change in wart or mole
Nagging cough, hoarseness

5. Antineoplastic Agent
•Don’t kill tumor cells directly; interrupt development, growth, 
spread of abnormal cells
•Normal Healthy cells
•Interfere with cell replication
•Antimetabolites interfere with DNA synthesis

6. Classification

7. According to Drug Acting
Directly on Cells
Alkalyting agent
•Nitrogen Mustard
e.g. : Mechlorethamine (Mustine HCL),
Cyclophosphamide, Ifosfamide.
•Ethylenimine
e.g. : Thio- TEPA
•Alkyl Sulphonate
e.g. : Busulfan
•Nitrosourea
e.g. : Carmustine, Lomustine
•Triazine
e.g. : Dacarbazine

8. Antimetabolites
Folate Antagonist
e.g.: Methotrixate
Purine Antagonist
e.g.: 6-Mercaptopurine, 6-thiogunine, Azathioprine
Pyrimidine Antagonist
e.g.: 5-Fluorouracil, Cytarabine
Vinka Alkaloids
e.g.: Vincristine, Vinblastine

9. Taxanes
e.g.: Paclitaxel
Epipodophyllotoxin
e.g.: Etoposide
Antibiotics
e.g.: Actinomycin, Doxorubicin, Daunorubicin,
Mitoxantrone, Bleomycins, Mithramycin.
Miscellaneous
e.g.: Hydroxyurea, Procarbazine,
L- Asparaginase, Cisplatin, Carboplatin.

10. Drug Altering Hormonal
milieu
•Glucocorticoids
e.g. : Prednisolone & Its Derivatives
•Estrogen
e.g.:  Fosfestrol, Ethinylestradiol
•Antiestrogen
e.g.:  Tomoxifen
•Antiandrogen
e.g.: Flutamide
•5a reductase inhibitor
e.g.: Finasteride
•GnRH analogues
e.g.: Naferelin, Goserelin

11. according to mechanism of
action
•Drugs affecting biosynthesis of nucleic acid
•Drugs destroying DNA structure and function
•Drugs interfering with transcription and blocking
RNA synthesis
•Drugs affecting protein synthesis
•Hormonal agents

12. Drug Affecting Nucleic Acid
Synthesis
Hydroxyurea
Drug Destroying DNA Structure
& its Function
Antitumor Antibiotics
Cisplatin &
carboplantin
Alkylating Agent
Camptothecins

13. Drugs interfering with
transcription
Dactinomycin
Doxorubicin
Daunorubicin
Drugs
affecting
protein
synthesis
L - Asparaginase
Podophyllotoxin : Teniposide
& Etoposide
Taxanes : Taxol & Taxotere
Vincristine & Vinblastin

14. Alkylating agents
HN
N
N
N
R
O
H
2N
Guanine in DNA
R-X HN
N
N
N
R
O
H
2N
R
HN
N
N
N
R
O
H
2N
R
HN
N
N
N
R
O
H
2N
R
Produce Highly reactive carbonium Ion
which transfer alkyl group to position 7
of guanine by the covalent bond.

15. Mechlorethamine:
• Ist Nitrogen Mustard , given by IV route
•Acute effects: nausea, vomiting & hemodynamic
changes.
•Dose: 0.1 mg/kg i.v. daily x 4 days
•Branded Name: Mustine 10 mg dry powder in vial
Cyclophosphamide:
•It is inactive & producing active metabolite. It has
prominent immunosuppressant property.
•Dose: Oral - 2-3 mg/kg/day, i.v. – every 10-15 mg/kg,
i.m. – 7-10 mg/kg/day
•Branded Name: Endoxan, Cycloxan 50 mg tab, 200, 500,
1000 mg inj.

16. Ifosfamide:
•Congener of Cyclophosphamide. It is utilize in
breast, testicular, head & neck carcinoma
•Dose: 200 mg
•Generic: Holoxan 1 g vial
Thiotepa( TSPA)
•It is a Ethylenimine
•Clinical uses: breast cancer, ovarian cancer, liver
cancer etc
•Toxicity: myelosuppression
•Dose: 0.3-0.4 mg/kg i.v.at 1-4 week interval
•Generic: Thiotepa 15 mg per vial inj
Busulfan (myleran)
•Good effect on chronic granulocytic leukemia
•Toxicity: myelosuppression

17. Nitrosourea
•Drugs : Carmustine, Lomustine
•Highly lipid-soluble, can cross BBB
•Treatment of brain tumor
•Dose: 100-130 mg orally
•Branded Name: Lomustine 40, 100 mg cap.
Methotrixate (MTX)
•Mechanism: inhibit dihydrofolate
reductase(DHFR), interfering synthesis of
thynidylate, Purine nucleotides
•Clinical uses: childhood acute lymphoblastic
leukemia and chorioepithelioma
•Toxicity: myelosuppression
•Dose : 2.5-15 mg/day
•Generic: Neotrexate 2.5 mg tab, 2 ml inj.

18. Antimetabolites
Mercaptopurine & thioguanine:
Converted into monoribonucleotides which inhibit the
conversion of IMP to adenine & guanine nucleotide.
Uses: acute leukemia & solid tumors
Dose: 6- Mercaptopurine – 2.5 mg/kg/day
6 Thioguanine: 100-200 mg/ day
Toxicity : myelosuppression and gastrointestinal
symptoms
Generic: Purinethol, Empurine – 50 mg Tab
Azathioprine:
Effects on T lymphocytes & suppress CMI
Use : immunosuppressant in organ transplantation & in
rheumatoid arthritis
Dose: 3-5 mg/kg/day

19. Pyrimidine antagonists
Fluorouracil （5-Fu）
Mechanism: convert to 5F-dUMP and inhibit thynidylate
synthase,block the synthesis of dTMP
Clinical uses: good effect on cancer of digestive tract, breast cancer
Toxicity : myelosuppression and mucositis
Dose: 1 gm orally on alternative days.
Branded Name: Fluracil, five fluro250 mg cap, 5 ml for i.v. inj.
Cytarabine （Ara-C ）
Ara-C →Ara-CMP →→Ara-CTP, competitively inhibit DNA
polymerase. The triphosphate of Cytarabine is an inhibitor of
DNA polymerase.
Clinical uses: acute granulocytic leukemia, mononuclearcyte
leukemia
Toxicity: severe myelosuppression , nausea etc
Dose: 1.5-3 mg/kg i.v. BD for 5-10 days
Branded Name: Cytarabine, cytosar & cytabin 100, 500, 1000 mg inj.

20. Vinka Alkaloids
Mechanism of action
Bind specifically to the micro tubular protein
tubulin in dimeric form, terminate assembly of
microtubules and result in mitotic arrest at
metaphase, cause dissolution of the mitotic
spindle and finally interfere with chromosome
segregation

21. Vincristine:
•Use: in childhood acute leukemia, Hodgkin's disease,
wilm’s tumor, ewing’s sarcoma & carcinoma lung.
•Dose: 1.5-2 mg/m
2
BSA i.v. weekly
•

Generic: Oncovin & cytocristin 1 mg/ vial inj
Vinblastin:
•Use :in Hodgkin's disease & testicular carcinoma.
•

Dose: 0.1-0.15 mg/kg
•Generic: Vinblastin 10 mg/vial inj
•Toxicity
VLB: nausea, vomiting, alopecia, myelosuppression
VCR: neurotoxicity , include muscle weakness,
peripheral neuritis and are flexia

22. Taxanes
Paclitaxal
•Mechanism: Enhance tubulin polymerization and promote
microtubule assembly
•Clinical uses: First choice for ovarian and advanced breast cancer
• Toxicity : Hypersensitivity, Peripheral neuropathy, Neutropenia ,
thrombocytopenia
•Dose: 175 mg by i.v. infusion over 3 hr, repeated every 3 weeks.
•Branded Name: Intaxel, paxtal 30 mg in 5 ml cremophor emulsion.
Docetaxel:
•More potent then Paclitaxel
•Use: breast & ovarian cancer. Also in gastric & head, neck carcinoma.
•Dose: 100 mg i.v over 1 hr repeat at 3 weeks
•Branded Name: Daxotel 20 mg, 80 mg inj.

23. Epipodophyllotoxin
Etoposide:
Semi synthetic derivative of podophyllotoxin. It arrest the
cells in G2 phase & cause the DNA breaks by affecting the
DNA topoisomerase II function .
Use: testicular tumor, lung cancer, Hodgkin's disease.
Dose: 50-100 mg /day oral for 5 days.
Branded Name: Peltasol 100 mg in 5 ml inj.

24. Camptothecin Analogues
Topotecan & Irinotecan are two semi synthetic analogues of Camptothecin.
They act similar as Etoposide but interact with different enzyme
topoisomerase I .
Topotecan:
Use: In metastatic carcinoma of ovary & small cell lung cancer.
AE: pain abdomen, vomiting & diarrhea
Dose: 1.5 mg i.v. over 30 min daily for 5 days.
Branded Name : Topotel 2.5 mg & 4.0 mg inj
Irinotecan:
It produces the cholinergic effects because it inhibit the AChE.
Use : Colorectal carcinoma, cancer lung/cervix/ovary
AE: body ach, weakness.
Dose: 125 mg i.v. over 90 min weekly for 4 weeks
Branded Name: Irinotel 40 mg, 100 mg inj.

25. Antibiotics
Dactinomycin
• Mechanism: bind tightly to double-stranded DNA
through interaction between adjacent guanine-
cytosine base pair, and inhibit all forms of DNA-
dependent RNA synthesis
•Clinical uses: narrow-spectrum
 In combination with surgery and Vincristine in
the adjuvant treatment of Wilm’s tumor
•Toxicity : evident myelosuppression
•Dose: 15 mg/kg i.v. daily for 5 days.
•Branded Name: 0.5 mg/vial inj.

26. Doxorubicin & Daunorubicin:
•Mechanism : Bind with high affinity to DNA through
intercalation and then block the synthesis of DNA and
RNA
•Clinical uses
ADM: one of the most important anticancer drugs ,
treatment of carcinoma of the breast, endometrium,
ovary, testicle, thyroid, lung and many sarcoma,
acute leukemia, Hodgkin’s disease
Daunorubicin: acute leukemia
•Dose: Doxorubicin 60-75 mg slow i.v. inj. every 3
weeks.
•Daunorubicin: 30-60 mg daily for 3 days repeat
weekly.
•Branded Name: Daunocin 20 mg/vial inj
•Adrimycin Doxorubicin Oncodria 10 mg, 50 mg per
vial inj.
Mitoxantrone :
•It is a analogue of doxorubicin
•Use : chronic myelogenous leukemia, non
Hodgkin’s lymphoma & carcinoma breast.
•Branded Name: 20 mg / 10 ml inj.

27. Bleomycin:
•It is mixture of glycopeptides antibiotics having anti
tumor activity.
•Dose: 30 mg twice weekly i.v./i.m.
•Branded Name: Bleocin, Oncobleo 15 mg inj.
Mitomycin:
•Use: In resistant cancer of stomach, cervix, colon, rectum,
bladder etc.
•Dose: 10 mg infused i.v. in one day.
•Branded name: Mytomycin C-2 10 mg inj.

28. Miscellaneous Cytotoxic Drugs
Hydroxyurea
Inhibit ribonucleotide reductase
Clinical uses: chronic granulocytic leukemia
Toxicity: bone marrow depression, nausea, vomiting
Dose: 20-30 mg/kg daily or 80 ml i.v. inj.
Branded Name: Cytodrox 500 mg cap.
Procarbazine:
Inhibit nucleic acid synthesis & cause chromosomal
damage.
Use : Oat cell carcinoma of lung.
Dose: 100-300 mg oral daily, maintenance dose 1-2
mg/kg/day
L- Asparaginase
it inhibit the synthesis of L- Asparagines to L-aspartic acid
which cause the cell death.
AE: Liver damage, pancreatitis & CNS symptoms (due to
protein synthesis)
Dose: 50-200 KU/kg i.v. daily for 2-4 weeks
Branded Name: Leunase 10,000 KU per vial inj.

29. Cisplatin & Carboplatin
•Clinical uses:
–Genitourinary cancers, particular ovarian and bladder cancer
–Testicular cancer: in combination with Vinblastin and
Bleomycin
•Toxicity
–Acute toxicity: nausea, vomiting
–Renal toxicity: hydration with saline infusion & diuretics
– Myelosuppression
Dose: 50-100 mg every 3-4 weeks
Branded name: Cisplatin, cisplate, Plantinex 10 mg, 50 mg vial.
Dose: 400 mg i.v. infusion over 15-60 min.
Branded Name: Oncocarbin 150 mg inj, kemocrab 150, 450
mg/vial inj.

30. Hormones
Glucocorticoids
Primarily used in childhood acute
leukemia & lymphomas .
Secondary effect in Breast cancer
Anti Androgen
Palliative effect in advanced / metastatic
cases because it increase the androgen
level.
Antiestrogen
Effective in positive estrogen receptor as
well as negative breast cancer in
postmenopausal women.
Estrogens
Use in carcinoma of male breast.
120-240 mg orally.
5a reductase inhibitor
Inhibit the conversion of testosterone to
dihydrotestosterone
GnRH agonists
Indirectly inhibit the secretion of androgen
/estrogen by suppressing the FSH & LH
has effect on prostate/breast
Progestin
Use in temporary remission in some cases
of advanced & metastatic endometrial
carcinoma

31. Side Effects
•Toxic effects on normal cells
•Bone marrow suppression
•Bleeding
•Stomatitis
•Nausea, vomiting, diarrhea resulting in weight
loss, malnutrition
•Hair loss
•Fetal malformations

32. Toxicity of the
anticancer drugs
Acute toxicity
Common toxicity
•Myelosuppression
•Gastrointestinal disturbance
•Alopecia
Specific toxicity
•Cardiac toxicity: Daunorubicin
•Liver toxicity: CTX, Dactinomycin
•Bladder toxicity: CTX
•Neurotoxicity: VCR
•Hypersensitivity: Taxol
Chronic toxicity
•Infertility, teratogenesis, carcinogenesis

33. Three Possible Benefits of
Antineoplastic
•Cure
•Palliation—reduce or alleviate
symptoms, but do not eradicate
tumor
•Prolongation of life