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BASIC INFORMATION

BASIC INFORMATION. Oncology – the study of the causes, properties, disease progressions and treatments of tumors & cancer Oncologist – physician who specializes in treating cancer Radiation oncologist – oncologist who specializes in using radiation to treat cancer

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BASIC INFORMATION

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  1. BASIC INFORMATION • Oncology – the study of the causes, properties, disease progressions and treatments of tumors & cancer • Oncologist – physician who specializes in treating cancer • Radiation oncologist – oncologist who specializes in using radiation to treat cancer • Radiotherapy – use of high energy x-rays, external beams, or radioactive materials placed directly on the tumor

  2. Human body contains 5x10¹³ cells Cells can either be - non dividing and terminally differentiated - continually proliferating - rest but may be recruited into cell cycle Tumour becomes clinically detectable when there is a mass of 10,000,000,000 cells (1g)

  3. Cancer Cells and Normal Cells CANCER CELLS NORMAL CELLS Frequent mitoses Normal cell Few mitoses Nucleus Bloodvessel Abnormal heterogeneous cells Oncogene expression is rare Intermittent or coordinated growth factor secretion Presence of tumor suppressor genes Loss of contact inhibition Increase in growth factor secretion Increase in oncogene expression Loss of tumor suppressor genes

  4. Many definitions for the word cancer: • Any definition must embody two characteristics: The property of uncontrollable growth of cells originating from normal tissue. The property of killing the host by means of local tissue invasion and/or distant spread (metastasis). • Cancer is a group of diseases characterized by uncontrolled cellular growth with local tissue invasion and/or systemic metastasis. Metastasis-spread of cells, from a primary tumor via the lymphatic and circulatory systems to a distant body part, where cells give rise to another cancer. Micro metastasis-metastasis too small to be detected by conventional diagnostic methods. Tumor-abnormal growth that can be benign or malignant.

  5. Chemotherapy • Goals - Cure - Control - Palliation

  6. Chemotherapy • Systemic treatment. • Chemical agents that kill rapidly growing cells. • Most act by damaging DNA. Indications: • Curative • Adjuvant • Neo-adjuvant • Palliative • Radiosensitisation Administration/Cycle: • One drug or a combination of drugs. • Given monthly, every 3 wks, weekly or daily depending on the disease and drug.

  7. Chemotherapy Strategies of administration • Monotherapy • Combination chemotherapy • Goal: maximize efficacy & minimize toxicity • Adjuvant chemotherapy • Goal: prevention of recurrence • Neoadjuvant chemotherapy • As a 2nd line in resistant ds. • Combined modality chemotherapy : • Chemotherapy + radiotherapy + surgery • Goal: obtain higher response rate

  8. How do Cytotoxic Agents Work? • Compete with DNA/RNA building blocks • Affect enzymes in DNA/RNA synthesis • Prevent cells from dividing

  9. Classification of Chemotherapeutic Agents • Alkylating Agents - Bind to DNA at N-7 position of Guanine - Interferes with DNA Replications (Nitrosoureas) (Antitumor antibiotics) - Interfere with nucleic acid synthesis and function, inhibits RNA synthesis and DNA synthesis • Antimetabolites - Resemble cellular metabolites (folic acid, purine, pyrimidine) - Interfere with DNA precursors & cellular metabolism • Plant Alkaloids- arrest or inhibits mitosis • Hormonal Therapy • Immunotherapeutic Agents • Miscellaneous

  10. The Cell Cycle DEATH G0 DIFFERENTIATION Mitosis M S DNA synthesis DNA content = 2n DNA content = 4n G2 G1

  11. Cycle-Specific Agents

  12. Alkylating Agents • Cyclophosphamide (Cytoxan) - Oral or IV administration - Side effects include myelosuppression, cystitis + bladder fibrosis, alopecia, hepatitis, gonadal dysfunction • Ifosphamide (Ifex) • Dacarbazine (DTIC) • Chlorambucil (Leukeran) • Melphalan (Alkeran, L-PAM) • Triethylenethiophosphoramide (TSPA, Thiotepa)

  13. Antibiotics Cell cycle nonspecific • Isolated from natural products from soil fungi • Mechanisms of action vary between classes with complex structures • Bleomycin • causes single and double stranded DNA breaks at sites of guanine • IV, IM, SC, or IP administration • Fever, dermatologic reactions, pulmonary toxicity,anaphylactic reactions • Actinomycin D (Dactinomycin, Cosmegen) • IV administration • Nausea/vomiting, skin necrosis, mucosal ulcerationmyelosuppression • Doxorubicin (Adriamycin) • IV administration • Myelosuppression, alopecia, cardiotoxicity, local vesicant, nausea/vomiting, mucosal ulcerations • Anthracyclines • Mitomycin • Mithramycin

  14. Antimetabolites • 5-Fluorouracil (5-FU, fluorouracil) • IV administration, Oral • Myelosuppression, nausea/vomiting, anorexia, alopecia • Methotrexate • IV,IM,intrathecal • Mucosal ulceration,myelosuppression, hepatotoxicity, allergic pneumonitis, meningeal irritation • Hydroxyurea (Hydrea) • Gemcitabine (Gemzar)

  15. Plant Alkaloids • Cell cycle specific • Taxanes Bind preferentially to the microtubules themselves resulting in polymerization and stabilization • Paclitaxel (taxol) Myelosuppression, alopecia, allergic reactions, cardiac arrhythmias • Docetaxel (Taxotere) Myelosuppression, alopecia, hypersensitivity reactions • Vinorelbine (Navelbine) Myelosuppression, constipation, peripheral neruopathy • Epipodophyllotoxins (Etoposide) Interact with DNA to cause single stranded breaks Myelosuppression, alopecia, hypotension • Vinca alkaloids • Vincristine (Oncovin) • Vinblastine (Velban)

  16. Paclitaxel & Docetaxel 1971 Pacific Yew: Taxus brevifolia OH 1986 European Yew: Taxus baccata

  17. Miscellaneous • Cisplatin - IV administration - Side effects include nephrotoxicity, tinnitus, hearing loss, and nausea/vomiting • Carboplatin - IV administration - Side effects include nephrotoxicity and ototoxicity, although less than with cisplatin • Topotecan • Irinotecan

  18. Dosage Calculation • Remember the Five Rights: medication, time, route, dose, patient • Calculate body surface area (BSA) • Recalculate drug and dosage against order • Check current labs (CBC,KFT,LFT) • Review drugs and potential side effects • Verify informed consent • Pre-medicate if ordered

  19. Routes of Chemo Therapy Administration • Oral • Intravenous • Intra-arterial • Isolated limb perfusion • Intracavity • Intra-peritoneal • Intraventricular • Intrathecal • Intravesical • Intraperitoneal • Intraventricular • intrapleural

  20. Side Effects of Chemotherapy • Bone Marrow Suppression - Anemia - Neutropenia - Granulocytopenia - Leukopenia - Thrombocytopenia • Gastrointestinal - NVD/Constip - Mucositis/stomatitis • Fatigue • Alopecia • Infection

  21. Anticancer drugs kill fast growing cells blood cells progenitors cells in the digestive tract reproductive system hair follicles Other tissues affected heart and lungs kidney and bladder nerve system Liver

  22. Epithelial Ovarian Cancer • Early stage high risk ovarian cancer • single or multiagent chemotherapy with varying combinations of cisplatin, carboplatin, cyclophosphamide, and paclitxel • Advanced stage ovarian cancer • Combination chemotherapy with paclitaxel and carboplatin (Cycloph. / Cisplat) • Value of intraperitonal chemotherapy controversial • Alternative regimens in topotecan, gemcitabine, and liposomal doxorubicin

  23. Germ Cell Tumors • Dysgerminomas • Highly sensitive to low dose radiation, but should not used due to decreased fertility • Combination chemotherapy with BEP, VBP, or VAC preferable for metastatic disease • Recurrence treated with BEP or POMB-ACE • Immature teratomas • Ia grade 1 do not require adjuvant chemotherapy • Higher grades and ANY patient with ascites should receive adjuvant chemotherapy, for which BEP is currently the preferred regimen • Endodermal sinus tumors All, regardless of stage, are treated with adjuvant chemotherapy using BEP or POMB-ACE following surgery • Embyonal carcinomas • Mixed germ cell tumors

  24. Sex Cord Stromal Tumors • Granulosa Cell Tumors • No evidence chemotherapy has benefit in stage I • Late recurrence • Stage II/IV: postoperative chemotherapy with BEP may increase Long term survival • Metastasis and recurrence: cyclophosphamide, melphalan, VAC, PAC, or BEP • Suboptimally debulked benefits from BEP • Sertoli-Leydig Tumors • Limited data but have shown that measurable disease aftersurgery may benefit from cisplatin with doxorubicinor ifosphamide

  25. Gestational Trophoblastic Neoplasia • Placental site trophoblastic tumors are insensitive to chemotherapy • Gestational trophoblastic neoplasia (According to FIGO Score) • (low risk <7) Single agent: MTX or Actinomycin-D • (high risk >7) combination chemotherapy (EMA-PE/CO)

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