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
Blood vessel
Abnormal
heterogeneous cells
Loss of contact inhibition
Increase in growth factor secretion
Increase in oncogene expression
Loss of tumor suppressor genes
Oncogene expression is rare
Intermittent or coordinated
growth factor secretion
Presence 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 G0 M S G2 G1 DEATH DIFFERENTIATION Mitosis
DNA synthesis
DNA content = 4n
G2 G1
DNA content = 2n

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 ulceration myelosuppression
Doxorubicin (Adriamycin)
Myelosuppression, alopecia, cardiotoxicity, local vesicant, nausea/vomiting, mucosal ulcerations
Anthracyclines
Mitomycin
Mithramycin

14. Antimetabolites 5-Fluorouracil (5-FU, fluorouracil) Methotrexate
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 Carboplatin Topotecan
- Side effects include nephrotoxicity, tinnitus, hearing loss, and nausea/vomiting
Carboplatin
- 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
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

24. 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

26. 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 after surgery may benefit from cisplatin with doxorubicin or ifosphamide

28. 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)