chemo

• Chemotherapy


  The treatment of cancer using specific chemical agents or drugs that are destructive to malignant cells and tissues
• Chemotherapy


  The treatment of disease using chemical agents or drugs that are selectively toxic to the causative agent of the disease, such as a virus, bacterium, or other microorganism
• Cancer


  A group of more than one hundred different diseases

  
• Cancer


  • Uncontrolled cellular growth
  • Local tissue invasion
  • Distant metastasis

  
• According to the incidence, epidemics of cancer can be classified

  
• According to the rate of death, epidemics of cancer can be classified

  
• Role of pharmacist in carcinology

  • Industrial role for investigations of new drugs
  • Choice of drug regimen
  • Therapeutic drug monitoring
  • Monitoring of drug toxicity
  • Providing drug information related to anticancer drugs
  • Monitoring of patient with providing supportive care issues as: Nutritional support, Management of cancer induced pain, Management of anticancer induced nausea and vomiting, Management of anticancer induced anemia, etc
• Carcinogens


  • Chemical carcinogens (Aniline causes bladder cancer, Benzene causes leukemia, Hormones such as anabolic steroid and oral contraceptives)
  • Physical carcinogens (UV light)
  • Biological carcinogens (Epstein virus causes lymphoma, Hepatitis B virus causes hepato-cellular cancer, Human papilloma virus causes cervix and uterine carcinoma, Human herpes virus 8 (HHV8) causes Kaposi's sarcoma)

  
• Carcinogenesis


  1. Initiation (Exposure to carcinogen -> genetic damage -> if not repaired -> irreversible cell mutation or initiated cell)

  2. Promotion (Growth of mutated or initiated cells to form preneoplastic cells)

  3. Conversion (Mutated or initiated or preneoplastic cells -> cancerous cells)

  4. Progression (Cancerous cells -> proliferation or uncontrolled cell growth -> local tissue invasion -> metastasis)

  
• Oncogenes


  Oncogenes developed from protoncogenes. Genetic alteration of protoncogenes results in activation of oncogenes which leads to dysregulation of normal cell growth with subsequent neoplasm formation. There is other types of Oncogenes which interfere with normal mechanism involved in programmed cell death or apoptosis. Over-expression of Oncogenes may result in immortal cells with increased potential of malignancy
• Tumor suppressor genes


  The normal function of these genes is to regulate and inhibit inappropriate cellular growth and proliferation. Tumor suppression genes loss, suppression or mutation results in loss of control over normal cell growth. The common examples are Anti-tumor protein gene 53 (P53 gene) that regulates apoptosis, inhibit angiogenesis and induce DNA repair, and Retinobastoma gene (RB1 gene) that is tumor suppressor protein which inhibit abnormal cell growth and disrupt cell cycle

  
• Anti-metastatic genes


  Genes that suppress metastasis
• Tumor growth


  • Early stage: Exponential growth, large portion of tumor cells actively dividing and rapidly growing, short doubling time, sensitive and responsive to chemotherapy
  • Late stage: Slow growth, large tumor mass, long doubling time, more resistant and less responsive to chemotherapy, characterized by angiogenesis

  
• Doubling time


  The time required for tumor to double its size. Most solid tumors have a doubling time of 2-3 months, except Burkitt's lymphoma which has a doubling time of 1 day

  
• Tumor burden


  It takes 10^9 cells (1 gram mass, 1 cm in diameter) for the tumor to be clinically detected. Such a tumor mass undergoes 30 doubling times. If it takes 10 additional doubling times, it reaches 1 kg in size (10^12 cells), which is considered lethal. As the tumor grows beyond 10^9 cells, the doubling time declines. Increased tumor burden makes cancer cells less responsive to chemotherapy

  
• Cell kill theory


  A certain percentage of cancer cells, not a certain number, will be killed with each course of chemotherapy. The tumor burden never reaches absolute zero, but tumors consisting of less than 10^4 cells can be eliminated by the host immune system, leading to a cure. Limitations are that it assumes all cancer cells are equally responsive, neglects drug resistance, and assumes no metastasis

  
• Metastasis


  • Spread of cancer cells from primary tumor site to distant sites. Once metastasis occurs, cure becomes very difficult. At least 60% of patients have some form of metastasis at diagnosis. Metastasis occurs through hematogenous spread and lymph nodes

  
• Tumor characteristics


  • Benign tumor (Non cancerous, localized mass, encapsulated, no tissue invasion, no metastasis, no recurrence)
  • Malignant tumor (Cancerous genetically unstable cells, retain properties of original tissue, anaplasia, tissue invasion, metastasis, relapse after remission)

  
• Tumor origin


  • Epithelial tissue -> carcinoma
  • Connective tissue as blood or bone -> sarcoma
  • Glandular tissues -> adenocarcinoma
  • Nervous and muscular tissues -> neuroblastoma

  
• Screening


  • Cancer is asymptomatic, early detection of small mass makes it more easily cured, small mass is more sensitive to chemotherapy than large mass

  
• Screening tests


  • Sigmoidscopy
  • Guiac test
  • Digital or finger rectal examination (DRE or FRE)
  • Tumor markers

  
• Prostate specific antigen (PSA)

  Helpful tumor marker used for early detection or screening of prostate cancer. Normal value is less than 4 ng/ml, but increased PSA does not necessarily confirm prostate cancer as it can also increase with BPH and prostatitis

  
• CA 125


  Tumor marker for ovarian cancer

  
• CA19-9


  Tumor marker for colon cancer and pancreatic cancer

  
• Human Epidermal Growth Factor Receptor 2 (HER2)

  Tumor marker mainly used for breast cancer
• CEA (carcino-embryonic antigen)


  Tumor marker associated with cancers of the pancreas, colon, lung, breast, and ovary. Normal range is <3 ng/ml for non-smokers and ≤5 ng/ml for smokers

  
• Alpha-Fetoprotein (AFP)


  Fetal serum protein, elevated in hepatocellular carcinoma, pregnancy, benign liver disease, pancreatic cancer
• Hormones as tumor markers


  • Natural hormones produced by tumors (Insulin by islet cell tumor, Calcitonin by medullary thyroid carcinoma, Catecholamine by pheochromocytoma)
  • Ectopic hormones not associated with malignancy of secretory organs (ACTH and ADH elevation in lung cancers)
• Enzymes as tumor markers

  • Acid Phosphatase (elevated in prostate cancer)
  • Neuron Specific Enolase (NSE, marker for tumors of central nervous system, neuroblastomas, lung cancer)

  
• Natural hormones


  • Insulin production by islet cell tumor
  • Calcitonin by medullary thyroid carcinoma
  • Catecholamine by pheochromocytoma or tumor of adrenal gland
• Ectopic hormones


  Hormones not associated with malignancy of its associated or secretory organs
• Ectopic hormones


  • Elevation of ACTH (adrinocorticotropic and ADH (antidiuretic hormone) in case of lung cancers
• Acid Phosphatase


  Enzyme found in high concentrations in the normal prostate as well as in primary and metastatic prostate cancers
• Acid Phosphatase may also originate from other tissues
• Neuron Specific Enolase (NSE)

  Enzyme found only in brain and neuroendocrine tissue, used as a marker for tumors of the central nervous system, neuroblastomas
• Galactosyl Transferase II


  In colon cancer its level correlated with the extent of disease and disease progression, in pancreatic cancer it was more sensitive and specific in distinguishing benign from malignant disease than other tests as AFP or CA 19-9 or CEA

  
• Monoclonal immunoglobulin


  Production is characteristic of myeloma, the amount serving as an index of tumor volume, response to treatment indicated by a fall, relapse by a rise

  
• Pap test for cervical cancer

  Speculum used to gather cells from the outer opening of the cervix of the uterus and the endocervix, cells examined under a microscope to look for abnormalities, aims to detect potentially pre-cancerous changes usually caused by sexually transmitted human papillomaviruses

  
• Breast examination


  • Breast self examination
  • Breast physical examination
  • Mammography

  
• Mammography


  Examination technique that sends X-rays through the breast tissue to obtain images, analyzed for abnormalities and assessed for changes from previous tests