Principles of Chemotherapy

[Audio] Good morning everyone! Today we will be discussing the use of chemotherapy to treat cancer. We'll look at the history, principles, and goals of chemotherapy, as well as its various effects on cancer and how clinicians use it with either curative or palliative intent. Let's get started!.

[Audio] I would like to emphasize that there are no conflicts of interest or financial relationships related to my presentation, nor will I discuss any off label use or investigational use in this presentation. Appreciate your comprehension..

[Audio] Understand the goals of chemotherapy and its application in the treatment of cancer, gain an awareness of the effect of chemotherapy on cancer cells and its use for curative or palliative purposes, learn about the Cell Kill Theory and its role in the principles of chemotherapy, and describe the principles of chemotherapy and how they are used - these are the objectives you should be able to accomplish by the end of the session..

[Audio] Chemotherapy has a lengthy past stretching back to the ancient Egyptians and Greeks. It wasn't until the 1940s, however, that its modern form was established. Over the years it has become an invaluable resource in treating cancer. This is due to its ability to interfere with the cancer cells replication and other normal functions which leads to cell death and shrinking of the tumor. One of the greatest advantages of chemotherapy is its systemic nature versus the localized treatment of radiotherapy and surgery. This allows doctors to devise drugs that are tailor-made for particular types of cancer - like acute leukemia and various types of solid tumors. This can be done with curative or palliative intent, hence the wide range of therapeutic options for clinicians. The field of chemotherapy is continually advancing, allowing for the proliferation of new drugs to combat cancer..

[Audio] Goals of chemotherapy can be divided into curative and palliative. In curative chemotherapy, a predetermined intensive regimen is utilized to increase chances of complete removal of cancer. On the other hand, with palliative intent, the clinician must take into consideration many factors to provide effective and humane relief of symptoms. Here, avoiding toxicity is of prime importance and the dosage and timing of chemotherapy may be modified as per the patient's requirements..

[Audio] Cell cycle duration is an important factor in determining the efficacy of chemotherapy. The cell cycle is the process by which a single cell duplicates its DNA, divides into two daughter cells, and prepares the daughter cells for division. In cancer cells, this process is often much faster than in normal cells, with completion of the cell cycle taking as little as a few hours, compared to days or even weeks for normal cells. As a result, cancer cells are more sensitive to chemotherapy than normal cells. The growth fraction of a tumor can also be used to predict the effectiveness of chemotherapeutic agents. Tumor cells in active phases of the cell cycle are more susceptible to chemotherapy, whereas those in G0 are protected. With a decrease in the number of cells in G0, the remaining cells will be more concentrated in the active phases, which makes them prone to the effects of chemotherapy. An understanding of the cell cycle is necessary for clinicians to understand the effects of chemotherapy and utilize it in a proper manner..

[Audio] The graph demonstrates that tumor growth is exponential in its early stages, however, this rate of growth decreases as the tumor enlarges. Most tumors have begun to plateau at the time of detection, which implies that tumors in the exponential growth phase will be more susceptible to chemotherapy as more cells are in the active phase of the cell cycle. Surgery is the typical first step in treating advanced ovarian cancer in order to remove the primary tumor and reduce the number of cells subject to chemotherapy. It is believed that when a tumor starts to shrink due to treatment, an increased number of cells enter the active cycle, thus making it more responsive to chemotherapy..

[Audio] Chemotherapy has been used for many years as a treatment option for malignant cancer. It is based on the concept of killing rapidly dividing cells, as cancer cells divide rapidly. The process of chemotherapy works by using drugs, called chemotherapeutic agents, to target and attack the rapidly dividing cells. Chemotherapeutic agents typically work by first-order kinetics to kill a constant fraction of cells rather than a constant number. This means that each dose of a chemotherapeutic agent will kill a certain fraction of the cells, but will not necessarily kill all of the cells. This helps in preventing the drug from becoming resistance to the drug. In general, the effectiveness of chemotherapy has been found to be inversely proportional to the number of viable cells present at the beginning of chemotherapy. To enhance the cell kill, chemotherapy can be used in combination with drugs that work in different phases of the cell cycle. Therefore, chemotherapy is typically used in cycles, as each cycle is likely to kill the majority of the cancer cells from that cycle. This is why a single course of chemotherapy may not be enough to eradicate all cancer cells, as the body’s immune system or additional cycles of chemotherapy will be needed to ensure the complete eradication of the cancer..

[Audio] This slide showcases the Cell Kill Theory and the effects it can have on patient survival. The red line illustrates what the tumour burden might look like in an untreated patient - the tumour is detected at 109 cells, the patient is symptomatic at 1010-1011 cells, and dies at 1012 cells. The dark blue line shows the effect of infrequent scheduling, low dosing and a late start of treatment on patient survival - it does not cure the patient but prolongs survival. The light blue line shows the effect of a more intensive treatment, with adequate dosing and an earlier start - this is successful in curing the patient. Finally, the green line indicates that with early surgical removal of the primary tumour and subsequent chemotherapy, the total duration of treatment needed need not be as long as with chemotherapy alone..

[Audio] Limit doses to avoid overtreatment in these cases..