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

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