Chemotherapy - Dra. Alabastro Flashcards
Etiology of cancer
characterized by a shift in the control mechanisms that govern cell proliferation and differentiation
PHASE OF CELL CYCLE: nuclear membrane breaks down, mitotic spindle forms, chromosomes condense
Mitotic Phase - Prophase
PHASE OF CELL CYCLE: chromosomes condense at the center
Mitotic Phase - Metaphase
PHASE OF CELL CYCLE: chromosomes separate into chromatids
Mitotic Phase - Anaphase
PHASE OF CELL CYCLE: cells divide into parent and daughter cells
Mitotic Phase - Telophase
PHASE OF CELL CYCLE: Resting phase
G0 Phase
PHASE OF CELL CYCLE: RNA synthesis
G1 Phase
PHASE OF CELL CYCLE: DNA Replication
Synthesis Phase
PHASE OF CELL CYCLE: Preparation for mitosis
G2 Phase
Crucial component of cells’ machinery for organizing and dividing chromosomes
Forms spindles during mitosis
Microtubules
Basis for advanced treatment therapy for cancer
Proteins in control of cell growth
Class 1 proteins
growth factors
Class 2 proteins
Receptors for growth factors and hormones
Class 3 proteins
Intracellular signal transducers
Class 4 proteins
Nuclear transcription factors
Class 5 proteins
cell-cycle control proteins
Factors affecting tissue growth
- Cell cycle time
- Growth fraction
- Total # of cells in the population
- Increased cell death rate
Stages of tumor growth
Lag Phase: cells try to accustom themselves
Log Phase: cells repeatedly double in number
Plateau Phase: leveling off of cell doubling
Causes of cancer cells overproduction
- Failure of abnormal cells to undergo apoptosis
- Inappropriate stimulation of cell proliferation by genetic abnormalities
- Abnormalities of tumor suppressor gene (p53)
- Tumor angiogenesis
Factor of tissue growth that determines MAXIMUM GROWTH RATE of tumor
Cell Cycle Time
Factor of tissue growth that determines portion of cells sensitive to drug
Growth Fraction
Factor of tissue growth that gives an index of how advanced the cancer is.
Total # of cells in population
Indications for Chemotherapy
- Cure certain malignancies
- Palliate symptoms
- Treat asymptomatic patients
- Allow less mutilating surgery
Contraindications to Chemotherapy
- Inadequate facilities
- Survival unlikely even if tumor shrinkage is accomplished
- Unlikely to obtain benefits because of severe debilitation
- Asymptomatic patient with slow growing incurable tumors
Primary treatment for advanced cancer for which no alternative treatment exists
Primary Induction
Patients with localized cancer for which alternative therapies exit but less than completely effective
Neoadjuvant example: CT, RT
Reduces the incidence of both local and systemic recurrence and to improve the overall survival
Adjuvant
CLASSIFICATION OF CELL-CYCLE SPECIFIC CHEMOTHERAPEUTIC DRUGS
- Antimetabolites
- Antitumor antibiotic
- Vinca alkaloids
- Epipodophyllotoxins
- Taxanes
CLASSIFICATION OF CHEMOTHERAPEUTIC DRUGS
Cell Cycle Specific Drugs
Cell Cycle non-specific drugs
Phase Specific Drugs
CLASSIFICATION OF CELL-CYCLE NON-SPECIFIC CHEMOTHERAPEUTIC DRUGS
- Alkylating Agents
- Anthracyclines
- Antitumor antibiotics
- Camptothecins
- Platinum Analogs
GOALS OF CANCER THERAPY
- Damage the DNA of the affected cancer cells
- Inhibit the synthesis of new DNA strands to stop the cell from replicating
- Stop mitosis
Why are combinations effective?
Prevents resistant clones Less cytotoxicity Biochemical enhancement of effects To have sanctuary access Rescue
Neutrophil count and platelet count should be modified when?
Absolute neutrophil count <120,000/mL
General Adverse Effects of CT drugs
Nausea & vomiting
Mucositis; Stomatitis
Baldness
Myelosuppression
When to modify drug dose in terms of renal toxicity?
Drugs that cause renal toxicity not administered unless creatinine clearance >55 ml/min (MTX; Cisplatin; Streptozocin)
Which drugs should have their dose reduced in cases of hepatic impairment
Vinca alkaloids
Anthracyclines
ALKYLATING AGENTS (give most commonly used drug): Nitrogen mustard
cyclophosphamide
ALKYLATING AGENTS (give most commonly used drug): Ethylenemelamine derivatives
Thiotepa
Altretamine
ALKYLATING AGENTS (give most commonly used drug): Alkyl Sulfonate
Busulfan
ALKYLATING AGENTS (give most commonly used drug): Triazene
Dacarbazine
ALKYLATING AGENTS (give most commonly used drug): Platinum Analogs
Cisplatin
Oxaloplatin
Adverse effects of platinum analogs
Nephrotoxicity
Ototoxicity
Neurotoxicity
Mechanism of action of ALKYLATING AGENTS
Attachment of alkyl groups to DNA bases at N7 guanine forms fragmented DNA
Characteristics of alkylating agents
Cell cycle non-specific
Phase non-specific
What should not be given in the administration of alkylating agents and why?
Do not give GLUTATHIONE as it can inactivate an alkylating agent
Which among alkylating agents has a direct vesicant effect on the skin?
Nitrogen mustard
Which alkylating agents are irritants?
Cisplatin
Dacarbazine
Indication of Chlorambucil (nitrogen mustard)
Chronic Lymphocytic Leukemia
Indication of cyclophosphamide IV/PO (nitrogen mustard)
BREAST
LYMPHOCYTIC LEUKEMIA
AE of cyclophosphamide IV/PO (nitrogen mustard)
Severe N/V
Alopecia
Hemorragic cystitis
Indication of THIOTEPA (ETHYLENEMELAMINE DERIVATIVE)
Breast and ovarian CA
Indication of Busulfan (alkyl sulfonate)
(CML) Chronic Myelogenous Leukemia
AE of Busulfan (alkyl sulfonate)
Pulmonary fibrosis
Interstitial Pneumonitis