Module 6 Anti-Cancer

Cont. Discuss appropriate pain management for cancer pain.

(ABCDE) -Assess often; ask what pain level is acceptable. -Believe the patient -Choose appropriate pain control measures. -Deliver interventions timely, dose often and around the clock. -Empower/educate patient and family to control treatment -Analgesics are the most powerful weapons for overcoming cancer pain (3 types) 1. Non-opioid analgesics (NSAIDS, acetaminophen) 2. Opioid analgesics (oxycodone, fentanyl, morphine) 3. Adjuvant analgesics (amitriptyline, carbamazepine, dextroamphetamine) -Select drug based on pain intensity. -Common practice to combine an opioid with a non-opioid -- combo can be more effective than either drug alone

Cont. Discuss the growth fraction and its relationship to chemotherapy (Dolan) High vs low growth fraction

-A tissue with a large percentage of proliferating cells and only a few cells in the resting phase (G0 cells) has a high growth fraction. -Tissue composed mostly of G0 cells have a low growth fraction.

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Regional drug delivery: Other specialized routes

-Anticancer agents can be administered via that portal vein to treat liver metastases and directly into the bladder for bladder cancer.

Cont. Discuss the major toxicities of chemotherapeutic drugs. Diarrhea

-Anticancer drugs impair absorption of fluids and other nutrients, causing diarrhea. -Diarrhea can be reduced with oral loperamide, a non absorbable opioid that slows gut motility by activating local opioid receptors.

MOA: Methotrexate

-Antimetabolite -S-phase specific -Folic acid analog; Inhibits dihydrofolic reductase which is necessary for conversion to active folic acid. -No folic acid = disruption of DNA synthesis & results in cell death.

Cont. Discuss obstacles to successful chemotherapy Limited drug access to tumor cells

-Because of a tumor's location or blood supply, drugs may have limited access to its cells. -Large solid tumors that poor vascularization, especially near the core. Therefore, cells within these tumors are difficult for drugs to reach. -Tumors in the CNS are hard to reach because it is difficult for most anticancer drugs to cross the BBB.

Cont. Discuss the growth fraction and its relationship to chemotherapy (Dolan) Why do we care about growth fraction?

-Because the growth fraction of a tissue is a MAJOR determining factors for how responsive a cancer may be to chemotherapy. -We need to understand growth fraction and the cell cycle to understand anti-cancer drugs.

Side effects: Methotrexate

-Bone marrow suppression -Pulmonary infiltrates and fibrosis -Oral and GI ulceration -Nausea and vomiting after administration -High doses can injure the kidneys -Death Fromm intestinal perforation and hemorrhagic enteritis -Fetal malformation and death

Cont. Discuss the major toxicities of chemotherapeutic drugs. Thrombocytopenia

-Bone marrow suppression can cause thrombocytopenia, thereby increasing the risk for serious bleeding. -Bleeding from the nose and gums is common. -Avoid drugs that promote bleeding (aspirin, anticoagulants). Can use acetaminophen. -For patients with severe thrombocytopenia, platelet infusions are the mainstay of treatment. -Caution should be exercised when performing procedures that might promote bleeding. -IV needles should be inserted with care, and IM injections should be avoided. -Blood pressure cuffs should be applied cautiously, because overinflation may cause bruising or bleeding.

Cont. Discuss the growth fraction and its relationship to chemotherapy (Dolan) How do cytotoxic drugs do their damage?

-By disrupting DNA synthesis or mitosis which are activities ONLY proliferating drugs carry out and therefore - we want cells to be in the proliferating phase and actively participating in the cell cycle in order for our drugs to be effective at killing these cells (aka a HIGH growth fraction).

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Cont. Combination therapy: 3. Reduced injury to normal cells

-By using a combination of drugs that do not have overlapping toxicities, we can achieve a greater anticancer effect than we could safely achieve using any of the other agents.

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Regional drug delivery

-By using special techniques for drug delivery, we can increase drug access to tumors, thereby increasing cell kill and reducing systemic toxicity. See below for options:

Cont. Discuss the major toxicities of chemotherapeutic drugs. Reproductive toxicity

-Can interfere with embryogenesis, causing death of the early embryo. -Fetal malformations -Highest risk in the 1st trimester, so avoid chemotherapy at this time. -After 18 weeks of gestation, risk is very low. -Drug effects on the ovaries may result in amenorrhea, menopausal symptoms, and atrophy of vaginal epithelium. -Cytotoxic drugs can cause irreversible sterility in males.

Cont. Discuss the major toxicities of chemotherapeutic drugs. Local injury from extravasation of vesicants

-Certain anticancer drugs, known as vesicants, are highly chemically reactive. -These drugs can cause severe local injury if they make direct contact with tissues. -Administered through IV, sites of previous irradiation should be avoided. -Leakage can produce high local concentrations, resulting in prolonged pain, infection, and loss of mobility. -Severe injury can lead to necrosis and sloughing, requiring surgical debridement and skin grafting. -If extravasation occurs, the infusion should be stopped immediately.

Cont. Discuss the growth fraction and its relationship to chemotherapy (Dolan) How does the growth fraction of a tissue within the body relate to chemotherapy?

-Chemotherapeutic drugs are MUCH MORE TOXIC to tissues that have a HIGH GROWTH FRACTION than tissues with a low growth fraction. -This is because cytotoxic drugs are more active against proliferating cells than against cells that are in the G0 or "resting" phase.

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Combination therapy

-Chemotherapy employing a combination of drugs is generally much more effective than chemotherapy with just one drug. Accordingly, most patient are treated with 2 or more agents. -By using a combo of drugs that DO NOT have overlapping toxicities, we can achieve a greater anticancer effect than we could with one drug alone. -Combination therapy offers 3 advantages: 1. Suppression of drug resistance 2. Increased cancer cell kill 3. Reduced injury to normal cells (see next 3 cards)

Cont. Discuss the major toxicities of chemotherapeutic drugs. Cont. Neutropenia

-Colony stimulating factors can minimize neutropenia. -3 of them -All 3 drugs act on the bone marrow to enhance granulocyte production. -Colony stimulating factors can decrease the incidence, magnitude, and duration of neutropenia. -As a result, they can decrease the incidence and severity of infection as well as the need for IV antibiotics and hospitalization.

Cont. Discuss the major toxicities of chemotherapeutic drugs. Nausea and vomiting

-Common -Immediate and drastic, may persist for hours or even days. -Discomfort is so great that refusal for further treatment occurs. -Nausea and vomiting associated with chemotherapy are much more severe than with other medications. -Nausea and vomiting can be reduced by premedication with antiemetics. -Antiemetics reduce anticipatory nausea and vomiting, prevent dehydration and malnutrition, and promote compliance with chemotherapy by reducing discomfort.

When discussing treatment options with a patient, it is important they understand all of the facts and risks vs. benefit of different treatments - treatment should bring about one of the following outcomes

-Curative -Palliative -Prolonged life

Therapeutic uses: Methotrexate

-Curative for women with choriocarcinoma -Non-Hodgkin's lymphoma -Acute lymphocytic leukemia of childhood -Large doses coupled with leucovorin have been employed to treat head and neck sarcomas and osteogenic sarcoma. -Rheumatoid arthritis -Crohn's disease -Psoriasis -Abortion

Cont. Discuss obstacles to successful chemotherapy Drug resistance

-Drug resistance can be a significant cause of therapeutic failure. -One mechanism of resistance, cellular production of a drug transport molecule, known as P-glycoprotein (pumps drugs out of the cell) can confer multiple drug resistance upon cells. -Drug resistance mechanisms, including production of P-glycoprotein, result from a change in DNA. -Drugs do not cause mutations that render cell resistance, drugs to create selection pressure favoring the drug resistant mutants. That is, by killing drug sensitive cells, anticancer agents create a competition free environment in which drug resistant mutants can flourish. -Because the presence of anticancer agents favors the growth of drug resistant clones, as therapy proceeds, the number of resistant cells will increase.

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Cont. Combination therapy: 1. Suppression of drug resistance

-Drug resistance occurs less frequently with multiple drug therapy than with single drug therapy. To understand why, we need to recall that resistance is acquired through random mutational events. -The probability of a cell undergoing 2 or more mutations, and therefore developing resistance to a combination of drugs, is smaller than the probability of a cell undergoing the single mutation needed for resistance to one drug. -Because drug resistance is reduced with combination therapy, the chances of therapeutic success are increased.

Cont. Discuss obstacles to successful chemotherapy Absence of true early detection

-Early detection of cancer with current screening methods is rare. Late detection has 3 important consequences: 1. By the time the primary tumor is discovered, metastases may have formed. 2. The tumor will be less responsive to drugs than it would have been at an earlier stage. 3. If the cancer has been present for a long time, the patient may be debilitated by the disease, and therefore less able to tolerate treatment.

Education: Methotrexate

-Educate women of childbearing age regarding potential fetal malformations and death when taking methotrexate. -Monitor kidney function; -Labs to monitor: CBC, Creatinine, BUN

Cont. Discuss the major toxicities of chemotherapeutic drugs. Hyperuricemia

-Excessive levels of uric acid in the blood. -Common following treatment for leukemias and lymphomas. -Major concern is injury to the kidneys secondary to deposition of uric acid crystals in renal tubules. The risk for this can be reduced by increasing water intake.

Etiology of cancer

-Genetic alterations caused by carcinogens, viruses, and radiation (x-rays, ultraviolet rays, radioisotopes). -Cancer cells alter their DNA and malignant changes result from a combo of activating oncogenes (cancer-causing genes resulting from proto-oncogenes being changes) and inactivating tumor suppressor genes (genes that prevent replication of cells that have become cancerous).

What is cancer?

-Group of more than 200 diseases characterized by uncontrolled and unregulated growth. -Most common: solid tumors of the breast, lung, prostate, colon, and rectum. Low growth fraction and respond poorly to drugs. -Rarer cancers: lymphocytic leukemia, Hodgkin's disease, certain testicular cancers. High growth fraction and respond well to drugs. -Genetic mutation, permanent DNA alteration. Begins in a single cell.

Cont. Discuss the growth fraction and its relationship to chemotherapy.

-Having established the relationship between growth fraction and drug sensitivity, we can apply this knowledge to predict how specific cancers will respond to chemotherapy. -The most common cancers (solid tumors of the breast, lung, prostate, colon, and rectum) have a low growth fraction, so they respond poorly to cytotoxic drugs. -In contrast, only some rarer cancers (like acute lymphocytic leukemia, Hodgkin's disease, and certain testicular cancers) have high growth fraction, so they tend to respond well to cytotoxic drugs. -So, this means that the most common cancers, which do not respond well to drugs, must be managed primarily with surgery. -Only a few cancers can be managed primarily with drugs.

Discuss safe dosage, handling, and administration of Cancer chemotherapy.

-High risk medications and specialized training it required to administer them. -Must be administered under direct supervision of an MD/DO. -These drugs are often mutagenic, teratogenic, and carcinogenic. -Direct contact with the skin, eyes, and mucous membrane can result in local injury (and can increase cancer risk if enough it absorbed). -Chemotherapy drugs administered via the IV route are vesicants (agents that cause blistering/irritation) and can cause serious local injury if extravasation occurs (leakage of potentially damaging medications into the extravascular tissue around the site of infusion). -To minimize the risk of injury, IV administration should be performed only into a vein with good blood flow. -Sites of previous irradiation should be avoided.

Discuss the major toxicities of chemotherapeutic drugs. Bone marrow suppression

-Highly toxic to bone marrow, a tissue with high proportion of proliferating cells. -Myelosuppression reduces the number of circulating neutrophils, platelets, and erythrocytes. -Loss of these cells has 3 major consequences: 1. Infections (from loss of neutrophils) 2. Bleeding (from loss of platelets) 3. Anemia (from loss of erythrocytes)

Therapeutic uses: Vincristine

-Hodgkins and non-hodgkins lymphomas -Lymphoma -Acute lymphocytic leukemia -Wilms' tumor -Rhabdomyosarcoma -Kaposi's sarcoma -Breast cancer -Bladder cancer -Bone marrow sparing -Ideal for combination therapy

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Cont. Combination therapy: 2. Increased cancer cell kill

-If we administer several anticancer drugs, each with a different mechanism of action, we will kill more malignant cells than if we use only one drug. -Therapeutic effects are enhanced because the combination attacks the cancer in 2 or more ways, not just one. -Greater cell kill is especially likely if a drug resistant subpopulation of cells is present.

Cont. Discuss the major toxicities of chemotherapeutic drugs. Stomatitis

-Inflammation of the oral mucosa. -Develops a few days after the onset of chemo and may persist for 2 or more weeks after treatment has ceased. -Can progress to denudation and ulceration, and is often complicated by infection. -Pain can be severe, inhibit eating, speaking, and swallowing. -Have good oral hygiene and a bland diet. -For a mild case, mouthwash containing a topical anesthetic plus an antihistamine can be used. -For severe cases, a systemic opioid may be needed. -In some cases, it is so severe that chemotherapy has to be interrupted.

Cont. Discuss obstacles to successful chemotherapy Toxicity to normal cells

-Injury to normal cells occur primarily in tissues where growth fraction is high (hair follicles, GI, bone marrow, and germinal epithelium of the testes. -Toxicity to normal cells is dose limiting. Meaning, dosage cannot exceed an amount that produces the maximally tolerated injury to normal cells. -Cytotoxic anticancer drugs are harmful to normal tissues because these drugs lack selective toxicity.

Discuss strategies for achieving maximum benefits from chemotherapy.

-Intermittent chemotherapy -Combination therapy -Optimizing dosing schedules -Regional drug delivery (see next cards)

Cont. Discuss the major toxicities of chemotherapeutic drugs. Anemia

-Less common than neutropenia or thrombocytopenia. -Can be treated with transfusions or erythropoietin (hormone that stimulates production of RBC's). -Erythropoietin cannot be used in patient with leukemias and other myeloid malignancies. -Erythropoietin shortens survival in all cancer patients, and is indicated only when the treatment goal is palliation. Do not use when the goal is cure or prolongation of life.

Education: Vincristine

-Must be given IV. -Good to give with other chemo meds as it causes very little bone marrow suppression.

Cont. Discuss the major toxicities of chemotherapeutic drugs. Neutropenia

-Neutrophils have critical role in fighting infections. -In patients with neutropenia, the incidence and severity of infection are increased. -Infection secondary to neutropenia ia one of the most serious complications of chemotherapy. -Onset it rapid and recovery is relatively quick. -Begins a few days after after dosing, and the lowest neutrophil count, called the nadir, occurs between day 10 and 14. -Recover a week or so later. -With some anticancer drugs, neutropenia is delayed. -Neutrophils counts must be monitored. Range is 2500-7000 cells/mm3. -Chemotherapy should be withheld until neutrophil counts return to normal. -Lack of neutrophils confounds the diagnosis of infections. Because the signs of infection depend on neutrophils being present. In the absence of neutrophils, fever is the principle early sign of infection.

Cont. Discuss the major toxicities of chemotherapeutic drugs. Cont. Neutropenia

-Patient should be made aware of their elevated risk of infection and taught how to minimize contagion. -They should be informed that fever may be the only indication of infection and report immediately. -The normal flora of the body is a major source of infection; the risk of acquiring an infection with these microbes can be reduced by daily examination and cleaning of the skin and oral cavity. -If neutropenic patients are hospitalized, every precaution must be taken to prevent nosocomial infections. -Patients should be given isolations room and monitored frequently for fever. -Certain foods (lettuce) abound in pathogenic bacteria should be avoided. -When a neutropenic patient develops and infections, immediate and vigorous interventions is requires. Specimens for culture should be taken, while waiting for results empiric therapy with IV antibiotic should be instituted.

Side effects: Vincristine

-Peripheral neuropathy -Sensory and motor nerve injury (decreased reflexes, weakness, paresthesias, sensory loss) nearly all pts experience this. -Injury to autonomic nerves (constipation, urinary hesitancy) -Severe local injury if extravasation occurs -Alopecia in 20% -Little bone marrow suppression (in comparison to others, this is why it is especially desirable for combined therapy.

Cont. Discuss the major toxicities of chemotherapeutic drugs. Alopecia

-Reversible hair loss results from injury to hair follicles. -Occurs with most cytotoxic anticancer drugs. -Begins 7-10 days after onset of treatment. -Regeneration 1-2 months after last course of treatment. -Forewarn patient -To some degree, hair loss can be prevented by cooling the scalp while chemotherapy is being administered. It is uncomfortable, causes headaches.

Cont. Discuss the growth fraction and its relationship to chemotherapy (Dolan) The cell cycle

-Sequence of events from one mitotic division to the next. -Cell cycle consist of 4 major phases: G1, S, G2, and M. -In any tissues, some cells are going through the cell cycle and some are "resting" aka in the G0 phase. -The ration of the cells that are actively going through the cell cycle (proliferating cells) to the cells that are resting (G0 cells) is the growth fraction.

Cont. Discuss obstacles to successful chemotherapy Solid tumors respond poorly

-Solid tumors have low growth fraction (high percentage of G0 cells) and generally respond poorly to cytotoxic drugs. There are 2 reasons for low responsiveness: 1. G0 cells do not perform the activities that most anticancer drugs are designed to disrupt. 2. Because G0 cells are not active participants in the cell cycle, they have time to repair drug induced damage before it can do them serious harm. -Not all solid tumors are equally unresponsive: Large tumors are less responsive than small ones. This difference occurs because, as solid tumors increase in size, more of their cells leave the cell cycle and enter G0, causing the growth fraction to decline even further. -The decrease in growth fraction in older tumors is a major reason why therapeutic success is more likely when cancers are detected early. -The drug sensitivity of a solid tumors can be enhanced by debulking. When a solid tumors is reduced by surgery or irradiation, many of the remaining cells leave G0 and reenter the cell cycle, thereby increasing their sensitivity to chemotherapy. This is known as recruitment.

Discuss the growth fraction and its relationship to chemotherapy.

-Some cells are going through the cell cycle, whereas others are "resting" in the G0. -The ratio of proliferating cells to G0 cells is called the growth fraction. -A tissue with a large percentage of proliferating cells and few cells in G0 has a high growth fraction. Conversely, a tissue composed mostly of G0 cells has a low growth fraction. -Chemotherapeutic drugs are much more toxic to tissues that have a high growth fraction than to tissues that have a low growth fraction. Why? Because most cytotoxic agents are more active against proliferating cells that agains cells in G0. -Proliferating cells are especially sensitive to chemotherapy because cytotoxic drugs usually act by disrupting DNA synthesis or mitosis (activities that only proliferating cells carry out). -These drugs are also toxic to normal tissues that have a high growth fraction (hair follicles, GI, bone marrow, and sperm forming cells).

Cont. Discuss appropriate pain management for cancer pain. WHO analgesic ladder for cancer pain management

-Steps of the ladder are associated with intensity of pain. -Patients pain level should be considered when deciding where to start on the ladder or how to proceed with pain analgesics. -Ex: if a patient is started on an NSAID, but there pain is increasing to a moderate rating, then we would move up the ladder and start the patient on an opioid analgesic to be given along with the non-opioid.

Discuss the major toxicities of chemotherapeutic drugs.

-The agents used for cancer chemotherapy constitute our most toxic group of medications. -Serious injury from chemotherapy occurs most often to tissues with high growth fraction (hair follicles, GI, bone marrow, sperm forming cells).

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Optimizing dosing schedules

-The dosing schedule is an important determinant of treatment outcome. -Matter of life and death due to dosing schedules. -Selection of the right drug for cancer therapy is only one of the requirements for success; those drugs must also be administered according to schedules that maximize beneficial effects. -Dosing schedules are especially critical for drugs that act during a specific phase of the cell cycle.

Keep in mind...

-The toxicity of anti-cancer drugs to normal tissues is one of the biggest obstacles to successful. chemotherapy. -Also, there are over 100 different types of cancers and treatments must be individualized, based on the specific biology of the cells involved.

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Intermittent chemotherapy

-The ultimate goal of chemotherapy is to produce 100% kill of neoplastic cells while causing limited injury to normal tissues. -When cytotoxic drugs are administered intermittently, normal cells have time to repopulate between rounds of therapy. -However, for this approach to succeed, normal cells must repopulate faster than malignant cells. -If malignant cells grow back faster than normal cells, there can be no reduction in tumor burden between treatment rounds.

Cont. Discuss obstacles to successful chemotherapy Cure requires 100% cell kill

-To cure a patient of cancer, we must eliminate every malignant cell. This usually cannot be achieved because the patient cannot tolerate the high doses of chemotherapy that it would take to kill every cancerous cell in the body. -Immune system is often suppressed as a result of the treatment, so we get very little assistance from the patient's own body in helping to destroy the cancerous cells (the body also does not recognize the cancerous cells as foreign and does not attack them). -It is difficult to truly know when we have 100% cell kill (< 1 billion cancer cells is undetectable by usual clinical methods).

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Regional drug delivery: Intrathecal delivery

-To enhance therapy of CNS cancers, drugs can be administered intrathecally (by injection directly into the subarachnoid space). -This technique passes the BBB, giving drugs better access to cells within the CNS.

Discuss obstacles to successful chemotherapy.

-Toxicity to normal cells -Cure required 100% cell kill -Absence of truly early detections -Solid tumors respons poorly -Drug resistance -Heterogeneity of tumor cells -Limited drug access to tumor cells

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Regional drug delivery: Intra-arterial delivery

-Treats solid tumors -Establishes a high concentration of the drug in the vicinity of the tumor while minimizing toxicity to the rest of the body. -Specific routes include carotid artery delivery (brain tumors) and hepatic artery delivery (liver metastases). -Only suitable for localized disease.

Cont. Discuss obstacles to successful chemotherapy Heterogeneity of tumor cells

-Tumors do not consist of a single population of identical cells. They are composed of subpopulations of dissimilar cells. -These subpopulations can differ in morphology, growth rate, and metastatic ability. More importantly, the can differ in responsiveness to drugs, primarily because of increased resistance. -As tumors age, cellular heterogeneity increase.

Cont. Discuss the growth fraction and its relationship to chemotherapy (Dolan) Understanding that cytotoxic drugs to treat cancer target tissues with high growth fraction helps us understand...

-Why these drugs are also TOXIC to NORMAL TISSUES that have a high growth fraction (cells that are proliferating often) such as bone marrow, GI epithelium, hair follicles, and sperm-forming cells - think about the common side effects of chemotherapy related to these effected tissues (makes sense!)

Anticancer drugs fall into 4 categories

1. Cytotoxic agents (drugs that kill cells directly) -this is what we are looking at in this module. 2. Hormones and hormone antagonists. 3. Biologic response modifiers (immunomodulating agents) 4. Target drugs (meds that bind with specific molecules that promote cancer growth.

Discuss appropriate pain management for cancer pain.

2 forms of pain for patients with cancer: 1. Nociceptive pain (more common) -Pain from injury to tissues -Somatic pain; injury to somatic tissues (bones, joints, muscles) , described as localized and sharp pain. -Visceral pain; injury to visceral organs (small intestines), described as diffuse, aching quality. -Nociceptive pain responds well to opioids. 2. Neuropathic pain -Pain from injury to peripheral nerves . -Described as burning, shooting, jabbing, tearing, numb, cold/ -Responds poorly to opioid analgesics, but instead response well to adjuvant analgesics (can be meds such as antidepressants, anticonvulsants, and local anesthetics/antidysrhythmics.

Cont. Neoplastic cell characteristics

Formation of metastases -Metastases are secondary tumors that appear at locations distant from the primary tumor site. -This is why you may hear "the patient has metastatic breast cancer", meaning tumors have formed somewhere else besides the breast. Immortality -Cancer cells can undergo endless divisions (most cancers have telomerase, an enzyme that allows for repeated division).

MOA: Vincristine

Mitotic Inhibitor M-phase specific Blocks mitosis by disrupting the assembly of microtubules

Neoplastic cell characteristics

Persistent proliferation -Cancer cells undergo unrestrained growth and division and in the absence of intervention and treatment, cancer cells will continue to grow until they cause death because there is no mechanism to stop their growth. Invasive growth -Normal cells are segregated from one another and do not impede the others territory - Cancer cells DO NOT care about boundaries and will invade into other tissues.

Cont. Discuss strategies for achieving maximum benefits from chemotherapy. Cont. Combination therapy and drug selection

So, there are 3 guidelines for selecting drugs in combinations: 1. Drugs should be effective by itself. 2. Each drug should have different mechanisms of action. 3. The drugs should have minimally overlapping toxicities.

Treatment options

Surgery -Often utilized for solid cancers (cancer in solid organs such as breast or prostate). Radiation -Often utilized for solid cancers. Drug therapy -Often utilized for disseminated cancers (those that have spread throughout the body such as leukemia or cancers that have metastasized) and some localized cancers (such as testicular carcinoma).

In summary; Cancer is

unregulated cell proliferation (rapid production).