Lecture 1.pptx PHCL 414 Pharmacotherapy-VIII

PHCL 414 Pharmacotherapy-VIII

1. Chemotherapy management Dr. Zabih Ullah Ph.D., EFRE (Belgium & Netherlands) Assistant Professor Email: [email protected]

2. Cancer definition Cancer is: Cancer is a large group of diseases that can start in almost any organ or tissue of the body when abnormal cells grow uncontrollably, go beyond their usual boundaries to invade adjoining parts of the body and/or spread to other organs. The latter process is called metastasizing and is a major cause of death from cancer. A neoplasm and malignant tumor are other common names for cancer.

3. Epidemiology Cancer is the second leading cause of death globally, accounting for an estimated 9.6 million deaths, or 1 in 6 deaths, in 2018. Lung, prostate, colorectal, stomach and liver cancer are the most common types of cancer in men, while breast, colorectal, lung, cervical and thyroid cancer are the most common among women.

4. Treatment approach 1- Chemoprevention(hormonal therapy) Use of medications to prevent cancer in high risk individual 2-Neoadjuvant therapy(chemotherapy before surgery) Use of one or more treatment modalities prior to the primary therapy, the goal is to debulk the tumor prior to surgery 3-Adjuvant therapy (chemotherapy, radiation) Therapy following the primary treatment modality, the goal is to target the minimal disease for patients at high risk for recurrence

5. Chemotherapy Chemotherapy is the use of drugs to destroy cancer cells. This type of cancer treatment works by keeping cancer cells from growing, dividing, and making more cells Chemotherapy target different phases of cell cycle and halt growth and division of the cell leading to cell death.

6. Phase of the cell cycle The cell cycle is a 4-stage process consisting of  Gap 1 (G1), synthesis (S), Gap 2 (G2), and mitosis (M) , which a cell undergoes as it grows and divides

7. Gap 0 (G) (1) Resting or dormant phase (2) Cells are temporarily out of the cycle and not actively proliferating; however, all other cellular activities occur. (3) Cells continue in G, until a stimulus causes them to reenter the cell cycle. (4) Because they are not actively proliferating, cells in this phase have some protection from exposure to cell cycle-specific chemotherapy agents.

8. Gap 1 (G1) (1) Postmitotic phase (2) Cells begin the first phase of reproduction and growth by synthesizing the proteins and RNA necessary for cell division.

9. Synthesis (S): DNA is replicated.

10. Gap 2 (G2) (1) Premitotic (or postsynthetic ) phase (2) The second phase of protein and RNA synthesis occurs. (3) Preparation for mitotic spindle formation occurs. (4) The cell is now prepared for division.

11. Mitosis (M) (1) Cell division occurs. (2) Shortest phase of the cell life cycle (3) Mitosis results in formation of two daughter cells with exact copies of the parent cell's DNA. Cells either reenter the cell cycle to reproduce or perform the specific functions of the tissue for which they are programmed

12. Classification of chemotherapy agents 1- Alkylating agents 2-Antimetabolities 3-Antitumor antibiotics 4-Miscellaneous agent 5-Nitrosoureas 6-Plant alkaloids

13. Alkylating agents a) First anticancer agents developed b) Cell cycle nonspecific c) Cause breakage in DNA helix strand, thereby interfering with DNA replication and result- ing in cell death d) Dose-limiting toxicities include bone mar- row suppression, gastrointestinal toxicities, and organ-specific toxicities (e.g., renal and hepatic, dependent on drug and dose). e) Other effects include carcinogenic and muta - genic effects and impaired fertility. Examples: bendamustine , busulfan , cyclophosphamide, cisplatin

14. Antimetabolities a) Block DNA and RNA growth by interfering with enzymes (e.g., antifolates , a type of anti- metabolite, interfere with the use of folic acid, which is necessary for normal cellular metabolism) b) Often divided into the following categories: folate analogs, purine analogs, adenosine analogs, pyrimidine analogs, and substituted ureas

15. Combination chemotherapy principles 1. Benefits a) Maximum cell kill within dose limits b) Broader coverage to overcome resistant cell lines 2. Drug selection for combination chemotherapy a) Are active as single agents b) Have differing mechanisms of action making them synergistic c) Have differing dose-limiting toxicities to allow therapeutic doses to be tolerated d) Have differing patterns of resistance e) Should be used at optimal schedule and dose Should be given at consistent intervals

16. Chemotherapy toxicity by system Some anticancer medicines may affect cells of vital organs, such as the heart, kidney, bladder, lungs, and nervous system. Chemo may have no serious long-term problems for many people. But in some cases, it can cause permanent changes or damage to the heart, lungs, nerves, kidneys, and reproductive or other organs

17. Chemotherapy toxicity by system