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. 6 11 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. • • • • • • • 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
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