This presentation is a short brief regarding Brain tumor and the leading molecules used in the treatment of Brain tumor as BBB is the major limiting factor for treating brain tumor.

1. Leading Substances for
Brain Tumour
By: SHIVANI CHAUHAN

2. • Introduction
• Definition
• Causes of Brain tumor
• Types of Brain tumor
• Chemotherapy in brain tumor
• Leading Substances for Brain tumor
Outlines

3. Brain tumor

4. Definition of Brain tumor
A brain tumor is a localized intracranial lesion which
occupies space with the skull and tends to cause a rise
in intracranial pressure.

5. Causes of Brain Cancer
 DNA Damage
 Radiation
 Genetics
 NF-1 (acoustic neuromas)
 Li Fraumeni syndrome
 Tuberous sclerosis (astrocytomas)
 Multiple endocrine neoplasia type-1(Pituitary
macroadenoma)
 Infection
 HIV

6. Distribution of Primary CNS
Tumors By Histology

7. I Primary Brain Tumors:
Benign
• Pituitary – adenoma,
Cranic-pharyngioma
• Meningioma
• Acoustic neuroma
• Dermoid tumor
Malignant:
• Glioma
• Primary cerebral Lymphoma
• Germinoma
• Pineoblastoma
• Medullablastoma

8. II Secondary Brain Tumors
• Lung
• Breast
• GI
• Any primary potentially

9. Chemotherapy
in
Brain Tumors

11. Timing of Chemotherapy
 Adjuvant
 After surgery or radiation
 Defined number of cycles
 Aim
Prolong time of recurrence
 Recurrence
 Number of cycles limited by side effects
 Aim
Improve symptoms, quality of life and slow progression

12. A BIT of HISTORY….
• Surgery & radiation mainstays of treatment (and still are)
• Chemotherapy options
• PCV standard of care for many years
• Procarbazine
• Carmustine
• Vincristine
• Single agent nitrosurea (Lomustine/carmustine) are equivalent

13. Rationale For The Use Of
Chemotherapy in Neuro-Oncology
 1 gram of tumor = one billion cells
 GTR = removal of 99% (990,000,000 cells)
 Still have 10,000,000 tumor cells
 Radiation may remove 99% (9,900,000 cells),
leaving 100,000 cells

14. Barriers to Use of Chemotherapy
 Uncommon (2% of all malignancies)
 Blood-brain barrier
 Interaction of chemotherapeutic agents with EIAC

15. Solutions to Barriers to Use of
Chemotherapy
 Lipophilic molecules (Nitrosureas)
 Small molecules (Gefitinib)
 Osmotic Blood Brain Barrier Disruption
 Design drugs that do not interfere with EIAC
medications
 Make chemotherapy drugs very expensive

16. How to overcome BBB ??
Newer delivery method includes:
 Interstitial chemotherapy uses disc-shaped polymer wafers (known as Gliadel
wafers) soaked with carmustine, the standard chemotherapeutic drug for brain
cancer.
 Intrathecal chemotherapy delivers chemotherapeutic drugs directly into the
spinal fluid
 Intra-arterial chemotherapy delivers high-dose chemotherapy into arteries in
the brain using tiny catheters.
 Convection-enhanced delivery (CED) involves placing catheters into the brain
tumor or nearby brain tissue to deliver slowly and continuously a cancer drug
over several days.

17. Chemotherapeutic Agents
 Carmustine (BCNU)
 Lomustine (CCNU)
 Procarbazine
 Temozolomide
 Vincristine
 Camptothecans (Irinotecan, Edotecarin)
 Gefitinib

18. Carmustine and Lomustine
 Highly lipophilic nitrosureas
 Hydrolysis in vivo to form reactive metabolites
 Metabolites cause alkylation and cross-linking of DNA
 CSF equilibrates within one hour to > 50% of plasma levels
 Metabolism = hepatic microsomal enzyme
 Excretion = predominantly renal

19. Nitrosurea Toxicities
 Dose limiting toxicity is myelosuppression
 Nadir 25-60 days, recovery 35-85 days
 Nausea and vomiting
 Dizziness, ataxia, lethargy, disorientation
 Pulmonary fibrosis (dose dependent)
 Infertility and mutagenesis
 Carmustine is a vesicant

20. Procarbazine
 Multiple sites of action (inhibits DNA, RNA and
protein synthesis)
 Rapid equilibration with CSF
 Metabolism = microsomal enzymes
 Excretion = predominately renal

21. Procarbazine Toxicities
 DLT = myelosuppression, nadir 14-21 days, recovery 28 days
 Nausea and vomiting
 CNS depression, lethargy, peripheral neuropathy
 Hypersensitivity pneumonitis
 Infertility, mutagenesis
 Radiation enhancer

22. Standard ones include:
Temozolomide
 Taken oral
 First approved in 1999 for adult patients with anaplastic astrocytoma that did
not respond to other treatments.
 In 2005, it was approved for use during and after radiation therapy for
patients newly diagnosed with glioblastoma multiforme.
 Adverse effects: Relatively minor, but may include constipation, nausea and
vomiting, fatigue, and headache..

23. Temozolomide
 Classification = alkylating agent
 Rapid conversion at physiologic pH to MTIC, CSF concentration is
30% of serum
 MTIC cytotoxicity due to methylation of DNA at the O6 position of
guanine
 Antitumor activity is schedule dependent
 Cytotoxicity influenced by levels of MGMT
 Levels not infuenced by cytochrome p450
 Renal and hepatic clearance minor

24. Treatment Schedule
*PCP prophylaxis was required for patients receiving TMZ during the concomitant phase

25. Significant Improvement in Survival

26. Gefitinib
 Potent and selective inhibitor of EGFR tyrosine kinase
 EGFR expression and over-expression in GBM other brain
cancers
 Over-expression correlated with poor prognosis in many
cancers
 Once-daily, oral dosing
 Lipophilic compound but CNS levels are low

27. THANK YOU
For any queries, please contact me at: shivanichauhan232@gmail.com