Principles of Chemotherapy
and Radiotherapy
Dr. Dehan Gunasekera
Consultant Oncologist
National Cancer Institute of Sri Lanka
Cancer Statistics
Adult cancers 90 %
Haematological malignancies 30 – 40 %
Solid tumours 60 –70 %
Childhood cancers 5 – 10 %
Haematological malignancies 60 – 70 %
Solid tumours 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 CancerPrimary 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.
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
a) “Coulomb-force interactions with the external
nuclear field” when b << a
b) “hard collision” when b ≈ a
c) “soft collision” when b >> a
Charged particleb
a
Undisturbed trajectory
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.
• Xray Chest 0 .25 mSv
• Mammogram 1.0 mSv
• CT Brain 50.0 mSv
• CT chest 35.0 mSv
• CT Abdomen 25.0 mSv
• Ba enema 9.0 mSv
• Ba Meal 5.0 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
Classification of Drugs used in
the Treatment of Cancer
• Alkylating agents
Nitrosoureas Carmustine
Nitrogen Mustards Cyclophosphomide
Metal salts Cisplatin
Triazene Temozolamide
• Antimetabolites
Antifolates Methotrexate
Purine analogs 6MP, 6TG, Fludarabine
Pyrimidine analogs Cytarabine
• Natural ProductsAntibiotics
Anthracyclins Epirubacin Non Anthracyclins 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 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 cancer-
chemoRT 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
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