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 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.

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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

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

• Chemotherapy

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

M

S

G2 G1

The Cell Cycle

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

Thank you