Chemotherapy Overview lecture notes.pptx

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1. Lecture-1: Ch emotherapy Overview Dr. Ali Alyahawi

2. Ch emotherapy is  a cancer treatment where medicine is used to kill cancer cells . There are many different types of chemotherapy medicine, but they all work in a similar way. They stop cancer cells reproducing, which prevents them from growing and spreading in the body

3. The choice of chemotherapy may depend on the following: Your cancer type: Some types of cancer, such as ovarian and pancreatic cancer, are almost always treated with chemotherapy. Other cancers, such as breast cancer, may use chemotherapy for certain subtypes or stages of cancer. Your cancer stage and grade: Because of its many side effects, chemotherapy is often used on hard-to-treat or aggressive cancers that are likely to spread or have already spread to other parts of the body. For cancer that has spread, the location or site of cancer spread: Certain chemotherapy drugs may work better in different organs. For example, the blood-brain barrier protects your brain by filtering out drugs. If cancer has spread to your brain, your oncologist may treat you with chemotherapy that is able to cross the blood-brain barrier. Your general health and other medical conditions: Chemotherapy can cause many side effects. Some drugs can affect the heart, liver, kidneys or other cells. Oncologists may choose specific chemotherapy agents for people with certain medical conditions, such as heart or kidney disease.

4. Pharmacologic Therapy Chemotherapy of cancer started in the early 1940s when nitrogen mustard was first administered to patients with lymphoma . Since then, numerous agents have been developed for the treatment of different cancers.

5. Dosing of Chemotherapy Chemotherapeutic agents typically have a very narrow therapeutic index. If too much is administered, the patient may suffer from fatal toxicities. If too little is given, the desired effect on cancer cells may not be achieved. Many chemotherapy agents have significant organ toxicities that preclude using steadily increasing doses to treat the cancer.

6. The doses of chemotherapy must be given at a frequency that allows the patient to recover from the toxicity of the chemotherapy; each period of chemotherapy dosing is referred to as a cycle. Each cycle of chemotherapy may have the same dosages; the dosages may be modified based on toxicity; or a chemotherapy regimen may alternate from one set of drugs given during the first, third, and fifth cycles to another set of different drugs given during the second, fourth, and sixth cycles. The dose density of chemotherapy refers to shortening of the period between cycles of chemotherapy.

7. This can accomplish two things: First, the tumor has less time between cycles of chemotherapy to grow, and second, patients receive the total number of required cycles in a shorter time period. Administration of dose-dense chemotherapy regimens often requires the use of colony-stimulating factors ( eg , filgrastim or granulocyte colony-stimulating factor [G-CSF]) to be administered. These agents shorten the duration and severity of neutropenia. The chemotherapy regimens that are dose dense tend to be adjuvant regimens, and the goal of therapy is cure.

8. When a chemotherapy regimen is used as palliative therapy (to control symptoms), the dosages of chemotherapy may be decreased based on toxicity or the interval between cycles may be lengthened to maintain quality of life. Patient and tumor biology also affect how cancer therapy is dosed. Patients with a uridine diphosphate–glucuronosyl-transferease1A1 enzyme (UGT1A1* 28) deficiency can have life-threatening diarrhea and complications from irinotecan related to a decreased ability to metabolize the parent drug.

9. The patient may have a blood test before irinotecan therapy to determine if this genetic mutation is present . In the case of some monoclonal antibodies, flow cytometry results reveal whether the tumor has the receptor where the drug will bind and exert the pharmacologic effect. The therapeutic uses of oncology drugs with valid genomic biomarkers will be discussed briefly in this chapter and in more detail in the following chapters.

10. Another consideration of chemotherapy administration is the patient. Factors that affect chemotherapy selection and dosing are age, concurrent disease states, and performance status. Performance status can be assessed through either the Eastern Cooperative Oncology Group (ECOG) Scale or the Karnofsky Scale. Performance status is a very important prognostic factor for many types of cancer. If a patient has renal dysfunction and the chemotherapy is eliminated primarily by the kidney, dosing adjustments will need to be made. If a patient has had a myocardial infarction recently or preexisting heart disease, the clinician will weigh the risks of anthracycline therapy against the benefit of the treatment of the cancer.

11. Another important consideration for treatment of cancers is reimbursement by third-party payers for compendia off-label use. Off-label use is when a medication is used to treat a cancer that is not an FDA-labeled indication. Because of rapid advancements in oncology, it is estimated that up to 75% of chemotherapy agents are prescribed “off-label.” Drugs used according to FDA-approved indications are usually reimbursed. If sufficient supportive literature exists and the use is supported by one of the Medicare-approved compendia ( eg , AHFS-DI, Clinical Pharmacology, DRUGDEX, NCCN, others), an insurer should cover the cost of the anticancer treatment that does not have an FDA indication.

12. During the time of chemotherapy administration, patients will likely experience various toxicities. The National Cancer Institute (NCI) has provided a standardized system for evaluating and grading the toxicity from chemotherapy to provide uniform grading of toxicity and evaluation of new agents and new regimens ( Table).

13. Combination Chemotherapy The underlying principles of using combination therapy are to use (1) agents with different pharmacologic actions, (2) agents with different organ toxicities, (3) agents that are active against the tumor and ideally synergistic when used together, and (4) agents that do not result in significant drug interactions (although these can be studied carefully and the interactions addressed). When two or more agents are used together, the risk of development of resistance may be lessened, but toxicity may be increased.

14. Traditional chemotherapy agents have some similar side effects, usually manifested on the most rapidly proliferating cells of the body. However, there are unique toxicities of various pharmacologic categories of antineoplastic agents. Anthracyclines ( eg , doxorubicin) have the potential to cause cardiac toxicity, which is related to the cumulative dose. Microtubule-targeting agents ( eg , vincristine) are associated with various forms of neurotoxicity. Alkylating agents ( eg , melphalan) are associated with secondary malignancies. - Currently, anticancer agents are categorized by the mechanism of action.