Antineoplastic drugs

• These are the drugs that either kill cancer cells or modify their growth.
• Cancer is a disease of cells characterized by progressive, persistent, perverted (abnormal), purposeless and uncontrolled proliferation of cells.
• Cancer can be benign or malignant:
• Benign: Cell growth as compact mass and remains at their site of action.
• Malignant: Growth of cells is uncontrolled. Cells can spread into surrounding tissue and spread to distant sites.

Note: Cell division cycle

7 warning signs of cancer

• Change in bowel or bladder habits.
• A sore that does not heal.
• Unusual bleeding or discharge.
• Thickening or lump in breast or elsewhere.
• Indigestion or difficulty in swallowing.
• Obvious change in a wart or mole.
• Nagging cough or hoarseness.

Characteristics of cancer cells

• Self sufficiency in growth signals.
• Insensitivity to antigrowth signals.
• Evading programmed cell death.
• Limitless replicative potential.
• Sustained angiogenesis.
• Tissue invasion and metastasis.

Classification of antineoplastic agents

• Biological alkylating agents: Chlorambucil, Busulfan, Cyclophosphamide
• Antimetabolites: Azathioprine, Fluorouracil, Methotrexate, Mercaptopurine
• Antitumor antibiotics: Mitomycin, Actinomycin, Daunorubicin, Doxorubicin
• Other plant products: Vincristine, Vinblastine, Taxol
• Enzyme: L- Asparaginase
• Miscellaneous: Cisplatin, Oxaliplatin

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Handling of anticancer drugs

• Handling of cytotoxic drugs should be done at the designated area.
• Always use PPE (Personal Protective Equipments) when handling oral and injectable hazardeous drugs.
• All mixing and preparation should be performed in specially designated Class II Type B Biological Safety Cabinet where air is exhausted through HEPA (High Efficiency Particulate Air) filter and is equipped with continuous monitoring.
• Cytotoxic drugs should be packaged in a labeled, leak proof container with outer bags.

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• Storage
• There should be designated area for storing cytotoxic drugs
• Refrigerators should be easy to clean type.
• Handling spillage
• After the spillage, contaminated area must be isolated and cleaned immediately.
• PPE must be worn during cleaning.
• The spilled substances should be soaked up with sufficient quantities of adsorbent material.
• The spill kit must be replaced immediately after use.

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• Handling body waste
• Urine, blood, faeces, vomit etc need to be treated with caution
• Double flush the toilet after the patient uses it.
• Avoid touching body wastes.
• Disposal
• Cytotoxic waste should be incinerated at high temperature (800-1200 °C) depending upon the product.

Cisplatin

Chemistry

• Chemically it is cis diamino dichloro platinium.

• Mechanism of action
• inhibits DNA synthesis; cross-links and denatures strands of DNA

• Physical properties
• Occurs as yellow or orange yellow crystalline powder.
• It is slightly soluble in water, insoluble in alcohol.
• It is sensitive to light and air.
• It is odorless.
• MP: 270-272°C

• Stability and Storage
• Store protected from light and air.

• Uses
• Metastatic testicular cancer
• Advanced bladder cancer
• Metastatic Ovarian carcinoma
• Metastatic osteogenic carcinoma (orphan)
• Squamous cell carcinoma (orphan)
• Malignant melanona (orphan)
• Anal cancer (orphan)

6-mercapto purine

• Chemistry
• It the derivative of purine where pyrimidine and imidazole rings are fused
• Thione (mercapto) group is present in position 6.

• Mechanism of action
• Purine antagonist, antineoplastic

• Physical properties
• Occurs as yellow crystallline powder.
• It is sensitive to light and air.
• It is insoluble in water and soluble in hot alcohol.
• Odorless or practically odorless.
• MP: 308°C

• Stability and Storage
• Store protected from light and air.

• Uses
• Acute lymphatic leukemia
• Crohn’s Disease
• Ulcerative colitis.

5 - Fluorouracil

• Chemistry
• It is the derivative of uracil (pyrimidine 2, 4 – dione)
• Fluoro group is present in position 5.

• Mechanism of action
• inhibits DNA synthesis during S phase by inhibition of thymidylate synthetase

• Physical properties
• Occurs as white or almost white crystalline powder.
• Sparangly soluble in water and slightly soluble in ethanol.
• It is sensitive to light and air.
• It is odorless.
• MP: 282-286°C

Stability and Storage

• Store protected from light and air.

• Uses
• Colon and rectum cancer
• Breast cancer
• Gastric cancer
• Pancreatic cancer
• Gliobastoma multiforme – cancer of astrocytes of brain.

Doxorubicin

Chemistry

• It is the derivative of 8,10 dihydro tetracene.
• Ketone groups are present at position 5 and 12.
• Methoxy group is present in position 4.
• Hydroxy group is present in position 6, 9 and 11.
• Hydroxy methyl carbonyl group is present at position 9.
• 4-amino, 5-hydroxy, 6-methyl oxane is linked to position 7 by glycosidic linkage.

Mechanism of action

• Intercalates between DNA base pairs.
• Impairs topoisomerase II function and inhibits replication and transcription.

Physical properties

• It is official as Doxorubicin Hydrochloride.
• It occurs as orange red crystalline powder.
• It is soluble in water, slightly soluble in methanol.
• It is hygroscopic in nature. It is also photosensitive.
• MP: 216 degree celsius.

Stability and Storage

• It is hygroscopic and photosensitive so it is stored in a tightly closed, light resistant container.

Uses

• Cancers of breast, ovary, prostrate, stomach, thyroid, small cell cancer of lung, squamous cell cancer of head and neck
• Hepatocellular carcinoma (Orphan)

Mitomycin

Chemistry

• It is the derivative of diazatetracyclotridecadiene.
• Ketone groups are present at position 10 and 13.
• Methyl group is present at position 12.
• Methoxy group is present at position 7.
• Methyl carbamate (Carbamoyloxy methyl) group is present at position 8.
• Amino group is present at position 11.

Mechanism of action

• crosslinks DNA, preventing replication and transcription.

Physical properties

• It occurs as blue violet crystalline powder.
• It is soluble in water and methanol.
• It is sensitive to heat. It is also sensitive to light and moisture.
• MP: 370 degree celsius.

Stability and Storage

• It is affected by light, heat and moisture. So it must be stored in tightly closed, light resistant container in a cold place.

Uses

• Stomach cancer
• Pancreatic cancer
• Anal cancer

Tamoxifen

Chemistry

• It is the derivative of dimethyl amino ethane.
• 1,2 diphenyl butenyl phenoxy group is attached to position 2 of dimethyl amino ethane.

Mechanism of action

• Selective estrogen receptor modulator. Non steroid with potent antiestrogenic effects in breast (but may be estrogen agonist in uterus)

Physical properties

• It is official as Tamoxifen citrate.
• It occurs as white or almost white crystalline powder.
• It is soluble in water and alcohol.
• It is sensitive to light and moisture.
• MP: 140-144 degree celsius

• Stability and Storage
• Store protected from light and air.

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Uses

• Breast cancer
• Breast cancer prevention
• Ovulation induction (Off label)
• Mastalgia (Off label)

Placitaxel

aka Taxol

It is the constituent derived from Taxus sps.

Chemistry

• Derivative of taxane
• 3-benzamido, 2-hydroxy, 3-phenyl propanoyloxy group is present at position 13.
• Acetyl, benzoyloxy, hydroxy, acetoxy, ketone and methyl groups are present at various positions.

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Mechanism of action

• prevents depolarization of cellular microtubules.

Physical properties

• Occurs as white or almost white crystalline powder.
• Sensitive to light and high temperature.
• Soluble in water and alcohol.
• Odorless
• MP: 216-217 degree celsius.

Stability and Storage

• It should be stored in well closed container protected from light at a temperature not exceeding 25 degree celsius.

Uses

• Breast cancer
• Ovarian cancer
• Non small cell lung cancer
• Pancreatic cancer

Vincristine

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Vincristine is a natural alkaloid isolated from the plant Vinca rosea

Chemistry

• It is the derivative of indole.
• Diazatetracyclononadecatetraene and diazapentacyclononadecatetraene rings are linked together.
• Methoxycarbonyl, acetoxy, formyl , methoxy, hydroxy, and ethyl groups are present in various positions.

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Mechanism of action

• acts in M and S phases by inhibiting microtubule formation

• Physical properties
• Occurs as white or almost white crystalline powder.
• Odorless
• Sensitive to heat, moisture and light.
• Freely soluble in water, slightly soluble in ethanol.
• MP: 218-220°C

• Stability and storage
• Store protected from light and moisture in a deep freezer (below °-18C)

• Uses
• Acute leukemia
• Hodgkins disease
• Non-hodgkin’s malignant lymphoma
• Rhabdomyosarcoma (cancer that affects muscle)
• Neuroblastoma (cancer of embryonic cell from which nerve fibres originate)
• Breast cancer (off label)
• Bladder cancer (off label)

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