Chemo Flashcards
Uncontrolled cell growth followed by a loss of function.
Cancer
What are the Basic Principles of Chemo Administration?
-Dosage is based on BSA
-Administration usually follows a schedule of Therapy/Recovery/Therapy
-Most agents are metabolized via biotransformation in the Liver
-Most agents are eliminated primarily in the urine. Some agents require Enterohepatic Circulation
-Bile acids are stored in the gallbladder
-During digestion, bile acids are absorbed through the gut mostly unconjugated (some conjugated)
-In the terminal ileum, the bile salts are reabsorbed and carried through the portal blood circulation to be reconjugated and secreted back into bile
Enterohepatic Circulation
What are the 4 Cancer causing Factors?
1) Environmental Exposure (smoking, radiation, asbestos)
2) Viruses (Hepatitis B&C, HIV, HPV, Epstein-Barr)
3) Oncogenes (cause cells designated for apoptosis to survive and proliferate instead)
4) Tumor Suppressor Genes (Usually found in combination with other genetic changes)
A gene that has the potential to cause cancer.
-Often mutated or expressed at high levels in tumor cells
Oncogene
A gene that protects a cell from one step on the path to cancer.
-If this gene mutates or loses function, the cell can progress to cancer.
Tumor Suppressor Genes
The primary treatment for patients who present with advanced Cancer for which no other treatment exists.
-Goals: relieve tumor related symptoms, improve quality of life, and prolong time to tumor progression
Primary Induction Chemotherapy
Treatment for patients who present with localized disease, but surgery and/or radiation are inadequate by themselves.
-Administered before the main treatment (surgery or radiation)
Neoadjuvant Chemotherapy
Applied after initial treatment for cancer, especially to suppress secondary tumor formation.
-Potentially curative following resection of the primary tumor
-Goals: reduce the incidence of both local & systemic recurrence and to improve the overall survival of patients
Adjuvant Chemotherapy
-Single drugs at clinically tolerable doses have been unable to cure cancer
-Benefits: provides maximum cell kill within the range of toxicity tolerated by the patient. Effective only if dosing is not compromised due to side effects.
-Provides a broader range of interaction between drugs and tumor cells
-May prevent/slow the subsequent development of drug resistance
-Ex: CHOP (Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin, Adreiamycin), Vincristine (Oncovin), Prednisone)
Multi-Drug Therapy (Combination Therapy)
Only use drugs with a favorable history for the specific tumor
-Complete remission vs. Partial remission
Efficacy
Toxic effects of selected agents should not overlap.
-Minimizes the lethal effects of multiple insults to the same organ or organ system
Toxicity
Combinations should be given at consistent intervals
-Recovery should be the shortest time necessary
-Gauged by the recovery of the most sensitive normal target tissue (typically bone marrow)
Optimum Scheduling
Balance of factors to allow for maximal effects
-Biochemical, Molecular, Pharmacokinetics
Mechanism of Interaction
Random changes in drugs may reduce the impact of the most effective agent.
-Decreases the potential for a cure
Avoidance of Arbitrary Dose Changes
Increase the doses of the respective agent
Dose Escalation
Evaluate the patient’s response and then schedule the next round of Chemo
Reducing the Interval
Applied to both single agents and combo agents, drugs are given in a specific order
Sequential Scheduling
Resistance in the absence of prior exposure to available standard agents
Primary resistance
Develops in response to exposure to a particular cancer agent or an entire drug class.
-Usually based on a specific change in the genetic machinery of a given tumor cell
-Amplification of one or more genes on the tumor
Acquired Resistance
Chemo cells go through Mitosis or Meiosis?
Mitosis
Cells start in mitosis, then go through differentiation.
1) G1: Synthesis of cellular components needed for DNA synthesis
2) S phase: DNA Synthesis
3) G2 phase: synthesis of cellular components for Mitosis
A cell is weakest when it’s reproducing
Cell Cycle
Anticancer agents that exert their effects on malignant cells in a particular phase
Cell Cycle Specific Drugs (CCS)
Anticancer agents that can sterilize a tumor whether it is cycling or resting (G0 phase)
-Cycling cells are more sensitive
Cell Cycle Nonspecific Drugs (CCNS)
Which Anti-cancer agents impact Nucleotide Biosynthesis?
Methotrexate
Which Anti-cancer agents impact pyrimidines?
5-FU
Which Anti-cancer agents impact DNA Replication?
1) Cyclophosphamide
2) Cisplatin
3) Bleomycin
4) Doxorubicin
5) Cytarabine
6) Carboplatin
Which Anti-cancer agents impact Microtubule Polymerization?
1) Vincristine
2) Vinblastine
3) Taxel
What are the two drugs that are Alkylating Agents?
Cisplatin and Carboplatin
-Kills tumor cells in all stages (Non-specific)
-Binds DNA through the formation of intrastrand and interstrand DNA cross-links
-Requires dose modification for renal dysfunction
Cisplatin & Carboplatin
What are the adverse effects associated with Cisplatin?
Nephrotoxicity, peripheral sensory neuropathy, and ototoxicity
What are the adverse effects associated with Carboplatin?
Myelosuppression
Significantly less renal & GI toxicity than Cisplatin
-Has largely replaced Cisplatin
What are the 3 drugs that are Antimetabolites?
Methotrexate, 5-FU, and Cytarabine
-Interferes with DNA, RNA, and protein formation
-Adverse effects: Mucositis, Diarrhea, and Myelosuppression
-Leucorvorin Rescue is used in the presence of high dose MTX to rescue normal cells from toxicity
Methotrexate (MTX)
-Inhibits DNA synthesis
-Extremely short 1/2 life (10-15 min)
-Adverse effects: Myelosuppression, mucositis, diarrhea, and hand-foot syndrome
5-Fluorouracil
-Inhibits DNA elongation, synthesis, and repair
-S phase Specific (!!!!!)
-Adverse Effects: cerebellar ataxia (inflamed/damaged cerebellar tissue causing dizziness) and myelosuppression
-Give continuously over 5-7 days due to rapid degradation**
Cytarabine
What are the 3 drugs that are the Natural Product Cancer Chemotherapy Agents?
1) Vinblastine
2) Vincristine
3) Paclitaxel
All inhibit mitosis, are metabolized by the Liver P450 system, and are excreted in feces.
-Inhibits mitosis; Metabolized by the Liver P450 system, excreted in feces (same with whole drug class)
-Adverse effects: Myelosuppression, SIADH, Alopecia
Vinblastine
-Inhibits mitosis; Metabolized by the Liver P450 system, excreted in feces (same with whole drug class)
-Adverse effects: Myelosuppression, SIADH, Alopecia
(Less Myelosuppression effects than Vinblastine)
Vincristine
-Inhibits mitosis; Metabolized by the Liver P450 system, excreted in feces (same with whole drug class)
-Adverse effects: arrhythmias, skin rash
-5% of patients have a hypersensitivity rxn. Premedicate with Benadryl, Decadron, and Zantac
Paclitaxel
What are the two drugs that are Anti-Tumor Antibiotics?
1) Bleomycin
2) Doxorubicin
-Inhibits DNA Biosynthesis
-Cell Cycle Specific for G2 (!!!)
-Adverse effects: Pulmonary Fibrosis
Bleomycin
-Oxygen free radicals bind to DNA, causing single and double strand DNA breaks
-Adverse effects: Cardiomyopathy
-Can also have radiation recall rxn (erythema and desquamation at the sites of prior radiation therapy)
Doxorubicin
What are some side effects of chemotherapy?
1) Mucositis (sloughing of tissues in oral cavity)
2) Hand & Foot Syndrome (painful, reversible. During administration of agent, skin sloughs off. High risk for infection. Prevent with ice packs during administration)
3) Alopecia
