Chemotherapy - Dra. Alabastro Flashcards
(134 cards)
1
Q
Etiology of cancer
A
characterized by a shift in the control mechanisms that govern cell proliferation and differentiation
2
Q
PHASE OF CELL CYCLE: nuclear membrane breaks down, mitotic spindle forms, chromosomes condense
A
Mitotic Phase - Prophase
3
Q
PHASE OF CELL CYCLE: chromosomes condense at the center
A
Mitotic Phase - Metaphase
4
Q
PHASE OF CELL CYCLE: chromosomes separate into chromatids
A
Mitotic Phase - Anaphase
5
Q
PHASE OF CELL CYCLE: cells divide into parent and daughter cells
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Mitotic Phase - Telophase
6
Q
PHASE OF CELL CYCLE: Resting phase
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G0 Phase
7
Q
PHASE OF CELL CYCLE: RNA synthesis
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G1 Phase
8
Q
PHASE OF CELL CYCLE: DNA Replication
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Synthesis Phase
9
Q
PHASE OF CELL CYCLE: Preparation for mitosis
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G2 Phase
10
Q
Crucial component of cells’ machinery for organizing and dividing chromosomes
Forms spindles during mitosis
A
Microtubules
11
Q
Basis for advanced treatment therapy for cancer
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Proteins in control of cell growth
12
Q
Class 1 proteins
A
growth factors
13
Q
Class 2 proteins
A
Receptors for growth factors and hormones
14
Q
Class 3 proteins
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Intracellular signal transducers
15
Q
Class 4 proteins
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Nuclear transcription factors
16
Q
Class 5 proteins
A
cell-cycle control proteins
17
Q
Factors affecting tissue growth
A
- Cell cycle time
- Growth fraction
- Total # of cells in the population
- Increased cell death rate
18
Q
Stages of tumor growth
A
Lag Phase: cells try to accustom themselves
Log Phase: cells repeatedly double in number
Plateau Phase: leveling off of cell doubling
19
Q
Causes of cancer cells overproduction
A
- Failure of abnormal cells to undergo apoptosis
- Inappropriate stimulation of cell proliferation by genetic abnormalities
- Abnormalities of tumor suppressor gene (p53)
- Tumor angiogenesis
20
Q
Factor of tissue growth that determines MAXIMUM GROWTH RATE of tumor
A
Cell Cycle Time
21
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Factor of tissue growth that determines portion of cells sensitive to drug
A
Growth Fraction
22
Q
Factor of tissue growth that gives an index of how advanced the cancer is.
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Total # of cells in population
23
Q
Indications for Chemotherapy
A
- Cure certain malignancies
- Palliate symptoms
- Treat asymptomatic patients
- Allow less mutilating surgery
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Q
Contraindications to Chemotherapy
A
- 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
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Primary treatment for advanced cancer for which no alternative treatment exists
Primary Induction
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Patients with localized cancer for which alternative therapies exit but less than completely effective
Neoadjuvant example: CT, RT
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Reduces the incidence of both local and systemic recurrence and to improve the overall survival
Adjuvant
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CLASSIFICATION OF CELL-CYCLE SPECIFIC CHEMOTHERAPEUTIC DRUGS
1. Antimetabolites
2. Antitumor antibiotic
3. Vinca alkaloids
4. Epipodophyllotoxins
5. Taxanes
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CLASSIFICATION OF CHEMOTHERAPEUTIC DRUGS
Cell Cycle Specific Drugs
Cell Cycle non-specific drugs
Phase Specific Drugs
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CLASSIFICATION OF CELL-CYCLE NON-SPECIFIC CHEMOTHERAPEUTIC DRUGS
1. Alkylating Agents
2. Anthracyclines
3. Antitumor antibiotics
4. Camptothecins
5. Platinum Analogs
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GOALS OF CANCER THERAPY
1. Damage the DNA of the affected cancer cells
2. Inhibit the synthesis of new DNA strands to stop the cell from replicating
3. Stop mitosis
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Why are combinations effective?
```
Prevents resistant clones
Less cytotoxicity
Biochemical enhancement of effects
To have sanctuary access
Rescue
```
33
Neutrophil count and platelet count should be modified when?
Absolute neutrophil count <120,000/mL
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General Adverse Effects of CT drugs
Nausea & vomiting
Mucositis; Stomatitis
Baldness
Myelosuppression
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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)
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Which drugs should have their dose reduced in cases of hepatic impairment
Vinca alkaloids
| Anthracyclines
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ALKYLATING AGENTS (give most commonly used drug):
Nitrogen mustard
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cyclophosphamide
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ALKYLATING AGENTS (give most commonly used drug):
Ethylenemelamine derivatives
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Thiotepa
| Altretamine
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ALKYLATING AGENTS (give most commonly used drug):
Alkyl Sulfonate
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Busulfan
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ALKYLATING AGENTS (give most commonly used drug):
Triazene
```
Dacarbazine
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ALKYLATING AGENTS (give most commonly used drug):
Platinum Analogs
```
Cisplatin
| Oxaloplatin
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Adverse effects of platinum analogs
Nephrotoxicity
Ototoxicity
Neurotoxicity
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Mechanism of action of ALKYLATING AGENTS
Attachment of alkyl groups to DNA bases at N7 guanine forms fragmented DNA
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Characteristics of alkylating agents
Cell cycle non-specific
| Phase non-specific
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What should not be given in the administration of alkylating agents and why?
Do not give GLUTATHIONE as it can inactivate an alkylating agent
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Which among alkylating agents has a direct vesicant effect on the skin?
Nitrogen mustard
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Which alkylating agents are irritants?
Cisplatin
| Dacarbazine
48
Indication of Chlorambucil (nitrogen mustard)
Chronic Lymphocytic Leukemia
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Indication of cyclophosphamide IV/PO (nitrogen mustard)
BREAST
| LYMPHOCYTIC LEUKEMIA
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AE of cyclophosphamide IV/PO (nitrogen mustard)
Severe N/V
Alopecia
Hemorragic cystitis
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Indication of THIOTEPA (ETHYLENEMELAMINE DERIVATIVE)
Breast and ovarian CA
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Indication of Busulfan (alkyl sulfonate)
(CML) Chronic Myelogenous Leukemia
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AE of Busulfan (alkyl sulfonate)
Pulmonary fibrosis
| Interstitial Pneumonitis
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Indication of Dacarbazine (triazene)
Melanoma
Hodgkin’s
Soft tissue sarcoma
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AE of Dacarbazine (triazene)
CNS depression
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Platinum analog that causes ototoxicity
Cisplatin
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Platinum analog that causes severe N/V
carboplatin
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Platinum analog indicated for COLON CA
Oxaliplatin IV
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Oxaliplatin is resistant to?
Cisplatin
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Alkylating Agent that causes SEVERE N/V
Cyclophosphamide
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Alkylating agent that causes alopecia
Cyclophosphamide
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Alkylating agent that causes hemorrhagic cystitis
Cyclophosphamide
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Alkylating agent that causes REVERSIBLE neuropathy
Oxaliplatin
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Alkylating agent that causes IRREVERSIBLE ototoxicity
Cisplatin
| Carboplatin
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MOA of NITROSOUREAS
alkylation and carbamoylatio
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Characteristic of nitrosoureas
Highly lipid soluble allowing them to cross BBB
| Has delayed myelosuppressive effects (6 - 8 weeks)
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Nitrosourea with minimal bone marrow toxicity
Streptozocin
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Irritant nitrosourea
Carmustine (BCNU)
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Newest nitrosourea that is sugar-containing and indicated for insulin secreting islet cell pancreatic CA
Streptozocin
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Prototype of antifolate (antimetabolite)
Methotrexate IV/PO
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MOA of antimetabolites
inhibits critical enzymes involved in nucleic acid (NA) synthesis or become incorporated into the NA and produces incorrect codes
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Antimetabolite that does not have a non-linear dose response curve
5-FU
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Antimetabolites with both IV/PO preparation
Methotrexate
| Mercaptopurine
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Antifolate Methotrexate indication
Acute Lymphoblastic Anemia
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Antifolate Methotrexate AE
Megaloblastic anemia
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5-Fluorouracil mainly indicated for?
Breast and colorectal CA
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5-Fluorouracil AE
Megaloblastic anemia
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DEOXYCYTIDINE ANALOG Cytarabine indication
Acute Myelogenous Leukemia (AML)
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PURINE ANTAGONIST mercaptopurine indication
Childhood acute leukemia
| AML
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MOA of VINCA ALKALOIDS (NATURAL PRODUCTS)
Inhibits tubulin polymerization resulting to metaphase arrest and inhibition of mitosis
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common toxicity of vinca alkaloids
Leukopenia
| Areflexia (neurotoxic)
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Prototype of vinca alkaloid which is indicated for Acute Lymphoblastic Leukemia
Vincristine
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Natural product that stabilizes microtubule polymer
Taxane
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Taxanes can only be given via?
IV
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How many percent of taxanes are excreted in the urine?
10% only
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Main toxicity of taxanes
bone marrow /myelosuppression
| Peripheral sensory neuropathy
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Paclitaxel mainly indicated for?
Breast and lung CA
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Toxicity of Paclitaxel
Myalgia
| arthralgia
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EPIPODOPHYLLOTOXIN MOA
Inhibits topoisomerase II to promote DNA breakage and arrest in S and early G2 phase
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Characteristic of EPIPODOPHYLLOTOXIN
Cell cycle specific
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EPIPODOPHYLLOTOXIN given as IV only
Teniposide
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Most common ADR of EPIPODOPHYLLOTOXIN
diarrhea
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EPIPODOPHYLLOTOXIN indicated for small and non-small lung CA
Etoposide
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EPIPODOPHYLLOTOXIN indicated ALL
Teniposide
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Natural product Topoisomerase I inhibitor which cuts and re-ligates ssDNA to cause damage
CAMPTOTHECINS
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How is IRINOTECAN (IV CAMPTOTHECIN) eliminated from the body?
Through bile and feces
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CAMPTOTHECIN for lung and ovarian CA
Toptecan
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CAMPTOTHECIN for colorectal CA
IRINOTECAN (IV)
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ANTICANCER ANTIBIOTICS that cause Topoisomerase II-dependent DNA cleavage & intercalate with DNA double helix
Anthracycline and Dactinomycin
100
ANTICANCER ANTIBIOTIC that complexes with Mg++ to DNA & Blocks DNA/RNA synthesis
Plicamycin
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ANTICANCER ANTIBIOTIC that causes cross links between complementary strands of DNA that impair replication
Mitomycin
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ANTICANCER ANTIBIOTIC that causes strand scission by interacting with O2 and iron
Bleomycin
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ANTICANCER ANTIBIOTIC that poorly crosses BBB
Bleomycin
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Cardiotoxic ANTICANCER ANTIBIOTICS
anthracyclines (DOXORUBICIN & DAUNOROBUCIN)
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ANTICANCER ANTIBIOTICS that cause pukmonary fibrosis
Bleomycin
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ANTICANCER ANTIBIOTIC that is hepatotoxic
Plicamycin
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ANDROGEN ANTAGONIST for prostatic CA
Flutamide
108
AE of FLUTAMIDE
Hot flashes
impotence
loss of libido
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Androgen hormone drug that causes cholestatic jaundice
Fluoxymesterone
110
AE of estrogen antagonist TAMOXIFEN
Hot flashes
| Osteoporosis
111
AE of steroids
Immunosuppression
112
AE of ANASTROZOLE (aromatase inhibitor)
Myelosuppression
113
Indication of ANASTROZOLE
Advanced ER/PR (+) non-tamoxifien responsive breast cacner
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Antiangiogenesis drug for colon CA
Bevacizumab
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Treatment for ADR of cisplatin or cytoprotective against cisplatin
AMIFOSTINE
116
Serotonin antagonist for mgt of N/V during CT
ONDANSETRON
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Management for myelosuppression AE
Give hematopoietic growth factors
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Drug combination for Cervical Cancer
Cisplatin or Carboplatin + 5FU
119
Drug combination for Colon CA
FOLFIRI: 5-FU + Leucovorin + IRInotecan/Topotecan
FOLFOX: 5-FU + Leucovorin + OXaliplatin
CapeOx:
Capecitabine + Oxaliplatin
CapeOx +/- bevacizumab
120
Drug combination for Acute Lymphocytic Leukemia (ALL) REMISSION
Vincristine + Prednisone
121
Drug combination for Acute Lymphocytic Leukemia (ALL) maintenance
6-mercaptopurine + Methotrexate + Cyclophosphamide
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Drug combination for Acute Myeloid Leukemia (AML)
Cytarabine + Doxorubicin
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Drug combination for Chronic Lymphocytic Leukemia (CLL)
Chlorambucil + Prednisone
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Drug combination for Chronic Myeloid Leukemia (CML)
Busulfan
125
Drug combination for adjuvant therapy to prevent relapse of BREAST CA
Anastrozole or letrozole/tamoxifen
126
Drug combination for BREAST CA with METS
AC: doxorubicin (Adriamycin) + cyclophosphamide + Paclitaxel/Docetaxel
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Drug combination for BREAST CA
CAF: cyclophosphamide + doxorubicin (Adriamycin) + 5-FU
AC: doxorubicin (Adriamycin) + cyclophosphamide
CMFP: cyclophosphamide + methotrexate + 5-FU + prednisone
128
Drug combination for LUNG CA
Etoposide + cisplatin/carboplatin
Topotecan + other agents
129
Most popular breakthrough in cancer therapy
Nanotechnology
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MOA of non-classic alkylating agents
DNA alkylation; methylates DNA and inhibits DNA synthesis and function
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MOA of Platinum Analogs
Forms intrastrands and interstrand DNA cross-links; binds to nuclear and cytoplasmic proteins
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Common AE of Nitrosoureas
Nausea and vomiting
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Common toxicity of anthracyclines
Vesicant
134
Aromatase inhibitors that cause myelosuppression
Anastrozole
Aminoglutethimide
Letrozole
