general oncology from devita presentation

1. PHARMACOLOGY AND USES
OF VINKA ALKALOIDS

2.  Naturally occurring
- Vincristine
- Vinblastine
 Semi-synthetic analogues
- Vinorelbine
- Vindesine
- Vinflunine

3. MECHANISM OF ACTION
 Periwinkle plant Catharanthus roseus
 Anti-microtubule agents
 Cell cycle-specific, active in the mitosis (M) phase of the
cell cycle.
 Inhibits tubulin polymerization, disrupting formation of
microtubule assembly during mitosis
 Arrest in cell division, ultimately leading to cell death.

6. MECHANISM OF RESISTANCE
 Mutations in ɑ- and ß-tubulin proteins - decreased
binding affinity for drug.
 Overexpression of p170 glycoprotein, encoded by the
MDR gene - enhanced drug efflux with decreased intra-
cellular accumulation of drug.

7. METABOLISM
 Metabolized by the hepatic P450 microsomal system
 75% drug excreted via fecal elimination
 Renal clearance – minor (<10% )

8. VINCRISTINE
 ONCOVIN, VCR
 White to off-white powder.
 Injection - single use only solution
 2 ml (1 mg, 2 mg) vials

9. INDICATIONS
 Acute and chronic lymphocytic leukemia
 Hodgkin’s and non-Hodgkin’s lymphoma
 Multiple myeloma
 Rhabdomyosarcoma
 Wilm’s tumor
 Neuroblastoma
 Ewing’s sarcoma

10. DOSAGE
 Adult - 0.5 – 1.4 mg/m2
 Pediatric - 1.5 – 2 mg/m2
 < 10 kg : 0.05 mg/kg per week
 Total individual dose should be limited to 2 mg to
prevent development of neurotoxicity.
 continuous infusion : 0.4 mg/day for 4 days as part of
VAD regimen.

11. DRUG INTERACATIONS
 Inhibit / induce cytochrome P450 system
 Cisplatin / Paclitaxel
 L-Asparginase
 Methotrexate
 Mitomycin - C

12. TOXICITY
 Neurotoxicity
- Dose limiting toxicity
- Peripheral neuropathy
- Autonomic nervous system dysfunction
- Cranial nerve palsies, ataxia, cortical blindness
 GIT
- constipation, abd pain, paralytic ileus
- Nausea, vomiting

13.  Vesicant
 Myelosuppression
 Reversible alopecia

14. DOSE MODIFICATIONS
 50% dose reduction – direct bilirubin > 3 mg /dl

15. CONTRAINDICATIONS
 Demyelinating forms of Charcot-Marie-Tooth syndrome
 Pregnancy category D
 Breastfeeding should be avoided

16. VINBLASTINE
 VELBAN, VLB
 White to off-white powder
 10 ml multidose vials ( 1mg / ml)

17. INDICATIONS
 Hodgkin’s and non-Hodgkin’s lymphoma
 Lymphocytic lymphoma
 Testicular cancer
 Breast cancer
 Kaposi’s sarcoma
 Renal cell carcinoma

18. DOSAGE
 Hodgkin’s lymphoma : 6 mg/m2 IV on day 1 and 15
(ABVD regimen)
 Testicular cancer : 0.15 mg/kg IV on day 1 and 2 (PVB
regimen)

19. TOXICITY
 Myelosuppression
- Dose-limiting
- Neutropenia
 Neurotoxicity
 GIT
 Hypertension
 Mucositis / stomatitis
 Reversible alopecia
 Vesicant

20. DOSE MODIFICATIONS
 50% dose reduction – direct bilirubin > 3 mg /dl

21. CONTRAINDICATIONS
 Severe neutropenia
 Pregnancy category D
 Breast feeding should be avoided

22. VINORELBINE
 NAVELBINE, VRL
 Semi-synthetic alkaloid
 Colourless to pale yellow solution
 1 ml (10 mg/ml) and 5 ml (50 mg/ 5 ml) vials

23. INDICATIONS
 Non-small cell lung cancer
- Cisplatin
- First line
- Locally advanced or metastatic
 Breast cancer
 Ovarian cancer

24. DOSAGE
 25 mg/m2 on days 1, 8, 15 and 21 of a 28 day cycle with
cisplatin 100 mg/m2 on day 1 only
 30 mg/m2 over 6-10 min once a week

25. SIDE EFFECTS
 Myelosuppression
- neutropenia
- dose-limiting toxicity, reversible
 Neurotoxicity
 GIT
 Vesicant
 Alopecia

26. DOSE MODIFICATIONS
 Hepatic toxicity
- 2.1 – 3.0 mg/dl : 50% dose
- > 3 mg/dl : 25% dose
 Hematologic toxicity
- < 1000/ cumm : do not administer
- 1000 – 1499 : 50% dose

27. CONTRAINDICATIONS
 Baseline neutrophil counts < 1000 cells/mm3
 Pregnancy category D
 Avoided in breast feeding

28. VINDESINE
 ELDISINE, VDS
 Semi-synthetic analogue
 Acute lymphoblastic lymphoma
 Blast crisis of CML
 Malignant melanoma unresponsive to other therapies
 Breast, colon, lung, renal cell cancer
 2-4 mg/m2 weekly

29. VINFLUNINE
 JAVLOR, VFL
 Semi-synthetic analogue
 Advanced or metastatic transitional cell carcinoma of the
urothelial tract after failure of platinum-containing
regimen
 320 mg/m2 IV every 3 weekly

30. LIPOSOMAL VINCRISTINE
 MARQIBO
 Vincristine encapsulated in sphingomyelin / cholesterol
liposomes, with an approx. liposome mean diameter of
100 nm.
 IV use
 5 mg / 5ml vials

31. INDICATIONS
 Adult patients with Philadelphia chromosome-negative,
acute lymphoblastic leukemia
- Second or greater relapse
- Disease has progressed following two or more anti-
leukemia therapies
- Clinical benefit such as improvement in overall survival
has not been verified

32. THANK YOU