1. Microtubule inhibitors

2. Microtubules Inhibitors
These drugs disrupt microtubules, which are structures that pull the cell apart when it divides
are derived from natural substances such as plant alkaloids

3. ANTIMICROTUBULE AGENTS

4. Microtubules Inhibitors
CCS
Vinca alkaloids
Vinblastine
Vincristine
Taxanes
Paclitaxel
Docetaxel
Podophyllotoxine

5. Vinblastine and Vincristine
Both drugs are cell cycle-specific because they block mitosis in metaphase
They bind to the microtubular protein, tubulin and thus preventing the cell from making the spindles
This results in arrest of mitosis at metaphase

6. Therapeutic Uses Adverse Effects:
Vinblastine is used in testicular carcinoma, Hodgkin’s disease
Vincristine is used in the treatment of acute leukemia in children, Wilm’s tumor, and Hodgkin’s and non-Hodgkin’s lymphomas
Adverse Effects:
Common adverse effects for both drugs include cellulitis or phlebitis if the drugs extra vasate during injection
Nausea, vomiting, diarrhea, and alopecia

7. Toxicity of Vinblastine & Vincristine
Myelo-supression
Peripheral neuropathy: Depressed deep tendon reflex, paresthesia, foot drop
Vincristine
NOT myelosuppressant

8. Taxanes
Interferes with cell division by keeping the spindles from being broken down (freeze)
Paclitaxel (Taxol) shows good activity against metastatic breast cancer and advanced ovarian cancer
Side effects; neutropenia ‼, peripheral neuropathy
Filgrastim ( granulocyte colony stimulating factor)

10. V. Miscellaneous Anticancer Agents

11. V- Miscellaneous Agents
L-Asparaginase
Hydroxyurea
Mitotane
Retenoic acid derivatives
Interferon

12. Asparagine is amino acid required for protein synthesis)
L- Asparaginase
Asparagine is amino acid required for protein synthesis)
Neoplastic cells require an external source of asparagine (from the plasma) because of their limited capacity to make sufficient asparagine to support growth

13. L-Asparaginase L-asparaginase
Asparagine aspartic acid
+Ammonia
L-asparaginase hydrolyzes serum asparagine and thus deprives the tumor cells of this nutrient required for protein synthesis
Most normal cells can synthesize asparagine and thus are less susceptible to the action of asparaginase

14. Theraputic uses:
L-asparginase is used to treat childhood acute lymphocytic leukemia in combination with vincristine and prednisone
Adverse effects: Hypersensitivity reactions, liver affection and pancreatitis

15. Hydroxyurea
Hydroxyurea interferes with conversion of ribonucleotides to deoxyribonucleotides by inhibiting Ribonucleotide Diphosphate Reductase. In addition, hydroxyurea blocks the incorporation of the thymidine nucleotide into the DNA strand.
Melanoma; recurrent metastatic or inoperable carcinoma of the ovary

16. Mitotane 
 Adrenal carcinoma
Reduces excessive steroid secretion
Retenoic acid derivatives
Remissions -- acute leukemia

17. Drug combinations

18. The administration of combinations of drugs in the treatment of cancer produces better results than a single drug
A combination of drugs with different toxic effects and affecting different biochemical pathways has higher anti-tumour activity without additive toxicity
Therapy is given intermittently to allow recovery of normal tissue i.e. bone marrow and immune system that has been affected by the drugs

19. Examples of drug combinations
Acute lymphocytic leukemia: vincristine, methotrexate and 6-mercaptopurine
Hodgkin's disease: vinblastine, doxorubicin and bleomycin
Non-Hodgkin's lymphomas: cyclophosphamide, doxorubicin, vincristine

20. Thank you