Cancer Chemotherapy Flashcards
Selective toxicity with neoplasias
Destroy neoplastic cells via selective killing versus normal cells, can be described in terms of chemotherapeutic index (CTI)
Chemotherapeutic index (CTI)
Equal to toxicity to cancer cells (lethal dose) / toxicity to normal cells, toxicity is measured by LD50
Importance of rapid and frequent chemotherapy treatments
Chemotherapy must be given to kill cells in a log fashion, rate of cancer growth is initially exponential then slows until a plateau is reached
Advantages of using combinations of anti-cancer drugs
Maximum cell killing within range of toxicity tolerated by the host, broader range of coverage of resistant cell lines in heterogenous tumors, prevents or slows the development of new drug resistant cell lines
Primary drug resistance
Absence of a response from the cancer on the first exposure to currently available standard agents
Acquired drug resistance
Cells become resistant after multiple exposures, develops in a number of drug sensitive tumor types, can be highly specific to a single drug is usually based on genetic changes in the tumor with amplification or increased expression or one or more genes
Multidrug resistant phenotype
Resistance to a variety of anticancer drugs of differing structures developing after exposure to a single agent, often associated with increased expression of MDR1 gene for cell surface glycoprotein involved in drug efflux
P-glycoprotein
Uses the energy of ATP to expel a variety of foreign molecules, overexpressed in multidrug resistant tumors, has two binding sites for ATP (only one involved in transport)
Bone marrow suppression (myelosuppression)
Low WBC counts, low RBC counts, low platelet counts
Low WBC counts
Increased susceptibility to infection, fever, sore throat, cough, SOB, nasal congestion, burning during urination, shaking chills
Low RBC counts
Fatigue, dizziness, headaches, irritability, SOB, tachycardia, tachypnea
Low platelet counts
Bruise easily, bleed longer, bleeding gums, nosebleeds, large bruises, internal bleeding
Serotonin antagonists given as anti-nausea agents in cancer patients
Dolasetron (Anzemet), Granisetron (Kytril), Ondansetron (Zofran), most effective for management of nausea and vomiting, first line antiemetic therapies
Action of antiemetics
Act in the chemoreceptor trigger zone (CTZ) and vestibular apparatus, the vomiting center in the medulla
Antidopaminergics given as anti-nausea agents in cancer patients
Prochlorperazine (Compazine), Fluphenazine (Permitil, Prolixin), Chlorpromazine (Thorazine), act by selectively depressing the CTZ, second line drugs for nausea
