Download Dr Dehan Gunasekera Consultant Radiation oncologist Teaching

Principles of Chemotherapy
and Radiotherapy
Dr. Dehan Gunasekera
Consultant Oncologist
National Cancer Institute of Sri Lanka
Treatment of Cancer
What are the types of cancers?
1. Solid tumours
2. Haematological malignancies
Cancer Statistics
Adult cancers
Haematological malignancies
Solid tumours
90 %
30 – 40 %
60 –70 %
Childhood cancers
Haematological malignancies
Solid tumours
5 – 10 %
60 – 70 %
30 – 40 %

Solid tumours and Haematological
malignancies are seen in Children and
Adults
– Children are treated by Paediatric
Oncologists
– Adults are treated by Adult Oncologists

Haematological malignancies in adults
are treated by
– Haemato-Oncologists

Who are Adult Oncologists?
• Radiation Oncologists (Clinical
Oncologists)
• Surgical Oncologists (Onco Surgeons)
• Gynecological Oncologists
• Haemato-Oncologists

Who treats children with malignancies?
• Paediatric Oncologists
Treatment of Cancer
Primary modalities of treatment of cancer
1. Surgery
- Surgical and Gynecological Oncologists
2. Radiotherapy
- Radiation Oncologists(Clinical Oncologists)
3. Chemotherapy
- Clinical Oncologist and Paediatric Oncologists
4. Combination of 2 and 3
Secondary modalities of Treatment
Biological therapy
1. Hormonal treatment
Tamoxifen for Breast carcinoma
Flutamide for Prostate Carcinoma
2. Immunological treatment
Interferon for CML
(Chronic Myeloid Leukaemia)
3. Monoclonal Antibodies
Rituximab for NHL
(Non Hodgkin’s Lymphoma)
How do we decide on the treatment
modality?
 Depends on the stage and type of the disease.
 The primary modality of treatment of
Haematological Malignancies of any stage is
Chemotherapy.
Leukaemia, Lymphoma
 Early stage solid tumours are treated Primarily
with Radiotherapy or Surgery.
 Advanced stage solid tumours are down staged
by Chemotherapy before Radiotherapy or
Surgery
• In early stage disease the treatment
modality will not be only dependent on the
stage .
• It will be decided on the functional and
cosmetic outcome of the treatment.
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Radiotherapy
• The goal of radiation therapy is to kill the
cancer cells while preventing damage to
healthy tissues.
• Depending on the location, size and type
of cancer, 3 techniques are required.
• Radiation therapy can be delivered in
three ways, externally ,internally and by
isotopes.
1. External beam radiotherapy
2. Brachytherapy
3. Radioactive isotopes
• In external beam radiotherapy the radiation
source is at a certain distance from the
patient and the target within the patient.
• Brachytherapy is the placement of radioactive
sources in or just next to a tumour.
The word brachytherapy comes from the
Greek "brachy" meaning short distance.
• Radioactive iodine for Thyroid Carcinoma
How does Radiotherapy work
Undisturbed
trajectory
Charged
particle
b
a
a) “Coulomb-force interactions with the external
nuclear field” when b << a
b) “hard collision” when b ≈ a
c) “soft collision” when b >> a
Internationally acceptable Doses of
Radiation to humans
• Effective dose in any one year should not
exceed 50 mSv
• Individual workers life time effective dose
should not exceed
Age in years X 10 mSv
• No occupational exposure should be
permitted until age of 18
Radiation Exposure
1 mSv is equal to exposure caused by traveling
4000 miles by aircraft.
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Xray Chest
Mammogram
CT Brain
CT chest
CT Abdomen
Ba enema
Ba Meal
0 .25
1.0
50.0
35.0
25.0
9.0
5.0
mSv
mSv
mSv
mSv
mSv
mSv
mSv
Sensitivity of tumours to RT
• Seminoma – highly sensitve to RT
• Melanoma – poorly or not sensitive to RT
• Squamous cell carcinoma – Moderately
sensitive to RT
• Anal Carcinoma – no longer a disease of
surgeons
• Stage 2 (and above), carcinoma cervix –
no longer a disease of Gynae-Oncologists
• Chemotherapy
Classification of Drugs used in
the Treatment of Cancer
• Alkylating agents
Nitrosoureas
Nitrogen Mustards
Metal salts
Triazene
Carmustine
Cyclophosphomide
Cisplatin
Temozolamide
• Antimetabolites
Antifolates
Purine analogs
Pyrimidine analogs
Methotrexate
6MP, 6TG, Fludarabine
Cytarabine
• Natural Products
Antibiotics
Anthracyclins
Non Anthracyclins
Epirubacin
Bleomycin
Enzymes
Asparaginase
Mitotic Inhibitors (Vinca Alkaloids)
Vincristine
Microtubule stabilizers (Taxenes)
Paclitaxel
Topoisomerase I Inhibtors
Irinotican
Topoisomerase II Inhibtors (Podophyllotoxins)
Etopside
• Hormones and hormone antagonists
Androgens
Deca Durobolin
Androgen Antagonist
Flutamide
Aromatase Inhibitors
Anastrazole
Corticosteroids
Dexamethasone
Oestrogens
Diethylstilbestrol
Selective Oestrogen
Receptor modulators (SERM) Tamoxifen
Leutinizing hormone
Releasing hormone agonists
Goserelin
Progestins
Megesterol Acetate
Thyroid hormones
Thyroxine
Molecularly targeted agents
• Monoclonal antibody
Rituximab – CD 20
Trastuzumab –Her2
• Tyrosine kinase inhibitor
Imitanib Mesylate
• Gene expression modulators
Retinoids
Biologic response modifiers
• Interferons
- Interferon 
• Interleukins
- Aldesleukin
• Colony stimulating factors
- Filgrastrim
- Erythropoietin
• Non specific immune modulators
- Thalidomide
Miscellaneous agents
• Substituted Urea
Hydroxyurea
• Bisphosphonates
Palmidronate
• Cytoprotectors
Mesna
• Somatostatin Analogs
Octreotide
• Methylhydrazine derivatives Procarbazine
• Photosensitizing agents
Porfimer
The Cell Cycle
M
G2
G1
S
The Practical aspects of
Pharmacokinetics and
Pharmacodynemics of Cytotoxic agents
• The cell cycle has 4 phases
• Drugs active in the G1 phase
(Preparation phase for DNA Synthesis)
- Asparaginase, Steroids
• Drugs active in the S phase
(DNA synthetic phase)
- Antimetabolites,Doxorubacin
• Drugs active in the G2 phase
(Resting phase prior to mitosis)
- Bleomycin, Irinotican
• Drugs active in the M phase (Mitotic phase)
- Vinca alkaloids, Taxenes,
- Podophyllotoxins
• Cell Cycle phase specific drugs have a plateau
in cell killing
•
Cell Cycle non phase specific drugs have a
linear dose responsive curve to cell killing
- Alkylating agents
•
Advantages of Combination Chemotherapy
1.
Maximum cell kill within tolerable toxicity
2.
Broader range of actions on resistant
cells
3.
Prevents new drug resistant cell lines
• Timing and dose of chemotherapeutic agents is
crucial in tumour control.
• Reduction in dose by 20% leads to loss of cure
rates of 50%.
• Inability to cycle chemotherapeutic agents at the
correct time will cause the tumour to grow and
develop drug resistance
Place for combined modality treatment
• Stage 3 and 4 Head and neck cancerchemoRT with cisplatin
• Nasopharyngeal carcinoma- chemoRT
with cisplatin
• Anal carcinoma- chemoRT with cisplatin
• Stage 2-4 Cacinoma cervix
Less established indications
• Carcinoma lung-ChemoRT with cisplatin
• Carcinoma Pancreas-ChemoRT with
cisplatin
• Carcinoma Bladder-ChemoRT with
cisplatin
Thank you