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SM_276b: Chemotherapy Basics Flashcards

1
Q

Describe systemic therapy for cancer

A

Systemic therapy is one of the major cancer treatment modalities

  • Reduce tumor size: can promote resection
  • Treat micro-metastatic disease: decreasing relapse
  • Prolong survival
  • Can be a curative treatment modality
  • Chemotherapy: cytotoxic, teratogenic, carcinogenic
  • Cancer treatment is fluid
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2
Q

Describe the drug development process

A

Drug development process

  1. Drug discovery
  2. Preclinical research
  3. Phase 1
  4. Phase 1
  5. Phase 3
  6. FDA approval (may be done earlier with accelerated FDA approval or adaptive trial design)
  7. Phase 4
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3
Q

Describe Phase I studies

A

Phase I studies

  • Goal: define toxicity (dose limiting doxicity, maximum tolerated dose)
  • Patient population: typically refractory patients, various tumor types
  • Dose escalation studies: often use a 3+3 design
  • Key characteristics: low number of patients, multiple doses used, toxicity endpoints
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4
Q

Describe Phase II studies

A

Phase II studies

  • Goals: provide general response rates at maximal tolerated dose, provide additional safety data
  • Patient population: small group of patients with specific tumor type
  • Key characteristics: more but not a ton of patients, may not provie clinical benefit
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5
Q

Describe Phase III studies

A

Phase III studies

  • Goal: efficacy in a specific line of therapy
  • Patient population: large cohort with specific type of cancer at same level of treatment
  • Key characteristics: large number of patients, usually a RCT with set control, gold standard points for assessment (overall survival, progression free survival)
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6
Q

Describe Phase IV studies

A

Phase IV studies

  • Post-market safety monitoring
  • Studies completed after drug has been FDA approved
  • Long term effect
  • Key characteristics: enormous number of patients, retrospective or FDA dictated RCT, gold standard points for assessment
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7
Q

Describe types of cancer treatment

A

Cancer treatment: CREST

  • Chemo
  • Radiation
  • Endocrine therapy
  • Surgical intervention
  • Targeted therapy
  • Immune therapy
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8
Q

Describe chemotherapy basics

A

Chemo basics

  • Goal: cure vs palliation
  • Requirements: killing most cancer cells, control most cancer cells, differentiation of cancer cells
  • Mechanism: exploit differences between cancer cells and normal host cells to develop anti-cancer agents
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9
Q

Describe combination chemo

A

Combination chemo

  • Used to overcome inherent drug resistance to single agents, delay / prevent acquired resistance
  • Which agonists?: single agent activity against tumor, differing mechanisms of action, non-overlapping toxicities
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10
Q

Describe neoadjuvant and adjuvant treatment

A
  • Neoadjuvant: given prior to removal of the tumor, to decrease tumor size in order to increase likelihood of complete resection
  • Adjuvant: given after removal of tumor, to eliminate micro-metastatic tumor deposits and decrease risk of tumor recurrence
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11
Q

Describe concurrent therapy

A

Concurrent therapy

  • Two treatment modalities at same time: chemo + radiation
  • Chemo radio sensitizes tumor to increase tumor killed
  • Increased risk of toxicities
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12
Q

Describe maintenance therapy

A

Maintenance therapy

  • After initial chemo treatment
  • Delays return of tumor
  • Less return of toxicities
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13
Q

Describe remission induction

A

Remission induction

  • First course of chemo in hematologic cancers
  • To eradicate 99% of initial tumor burden and restore normal hematopoiesis and performance status
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14
Q

Describe consolidation therapy

A

Consolidation therapy

  • During remission
  • Administered at high level of intensity
  • To reduce leukemic burden and decrease likelihood of relapse
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15
Q

____ and ____ are important dosing considerations

A

Dose intensity and density are important dosing considerations

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16
Q

Describe doxorubicin + cyclophosphamide dosing

A

Doxorubicin + cyclophosphamide dosing

  • Traditional dosing: doxorubicin 60 mg/m2 IVP on day 1 + cyclophosphamide 600 mg/m2 IV on Day 1 of every 21 day cycle
  • Dose dense: doxorubicin 60 mg/m2 IVP on day 1 + cyclophosphamide 600 mg/m2 IV on Day 1 of every 14 day cycle
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17
Q

Pharmacokinetics is ___

A

Pharmacokinetics is what body does to drug

  • ADME: absorption, distribution, metabolism, and excretion
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18
Q

Pharmacodynamics is ___

A

Pharmacodynamics is what drug does to the body

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19
Q

Describe cell cycle

A

Cell cycle

  • G0: cell cycle arrest
  • G1: cellular contents, excluding chromosomes, are duplicated
  • S: each of 46 chromosomes is duplicated by the cell
  • G2: cell double checks the duplicated chromosomes for error and makes repairs
  • Mitosis
  • Cytokinesis
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20
Q

___ is a chemotherapeutic agent that targets G1

A

Asparaginase is a chemotherapeutic agent that targets G1

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21
Q

___ and ___ are chemotherapeutic agent that target S

A

Antimetabolites and topoisomerase-I inhibitors are chemotherapeutic agents that target S

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22
Q

___ and ___ are chemotherapeutic agents that target G2

A

Epipodophyllotoxins and anthracenediones are chemotherapeutic agents that target G2

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23
Q

____ are chemotherapeutic agents that target M

A

Antimicrotubule agents are chemotherapeutic agents that target M

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24
Q

Describe chemotherapy classes

A

Chemotherapy classes

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25
\_\_\_ and ___ are cell cycle nonspecific chemotherapeutic agents
Alkylating agents and anthracyclines are cell cycle nonspecific chemotherapeutic agents
26
Describe types of alkylating agents
Alkylating agents
27
Describe alkylating agents
Alkylating agents * Reactive carbonium ion covalently binds to phosphates, amines, sulfhydryl, and hydroxyl groups * N7 guanine is the main alkylation site: inhibit DNA transcription and replication -\> mispair DNA, strand breakage -\> apoptosis * Toxicities: myelosuppression, CINV, mucositis
28
Describe alkylating agent toxicities
Alkylating agent toxicities * Alkyl sulfonates (busulfan): pulmonary toxicity * Nitrogen mustards (cyclophosphamide, ifosfamide): pro-drugs, hemorrhagic cystitis * Nitrosureas (carmustine, lomustine): pulmonary fibrosis
29
Platinum alkylating agents are \_\_\_, \_\_\_, and \_\_\_
Platinum alkylating agents are cisplatin, carboplatin, and oxaliplatin Metal adducts that cross-link DNA
30
Carboplatin has toxicity of \_\_\_\_
Carboplatin has toxicity of thrombocytopenia (myelosuppression)
31
Oxaliplatin toxicity is \_\_\_
Oxaliplatin toxicity is neurotoxicity (cold sensitivity, peripheral neuropathy)
32
Cisplatin toxicities are ____ and \_\_\_\_
Cisplatin toxicities are nephrotoxicity and delayed CINV
33
Alkyl sulfonates (busulfan) have toxicity of \_\_\_
Alkyl sulfonates (busulfan) have toxicity of pulmonary toxicity
34
Nitrogen mustards (cyclophosphamide, ifosfamide) are ___ and have toxicity of \_\_\_
Nitrogen mustards (cyclophosphamide, ifosfamide) are pro-drugs and have toxicity of hemorrhagic cystitis
35
Nitrosureas (carmustine, lomustine) have toxicity of \_\_\_
Nitrosureas (carmustine, lomustine) have toxicity of pulmonary fibrosis
36
Describe types of antimetabolites
Antimetabolites
37
Describe antimetabolites
Antimetabolites * Analogs in DNA and RNA pathways to inhibit synthesis of nucleic acids or incorporate into DNA or RNA which result in defective product * Myelosuppression
38
Purine antagonists (mercaptopurine and thioguianine) ___ and are \_\_\_
Purine antagonists (mercaptopurine and thioguianine) inhibit de novo purine synthesis and are metabolized by thiopurine methyltransferase * Thiopurine methyltransferase has polymorphisms
39
Purine analogs (cladribine, fludarabine, clofarabine, and pentostatin) \_\_\_\_
Purine analogs (cladribine, fludarabine, clofarabine, and pentostatin) mimic deoxyadenosine * Myelosuppression
40
Pyrimidine analogs (capecitabine, fluorouracil, gemcitabine, cyarabine, azacytidine, and decitabine) mimic \_\_\_
Pyrimidine analogs (capecitabine, fluorouracil, gemcitabine, cyarabine, azacytidine, and decitabine) mimic pyrimidines * Capacitabine and fluorouracil lead to hand foot syndrome, mucositis, and diarrhea
41
Describe azacitidine and decitabine
Azacitidine and decitabine * Hypomethylation of DNA by inhibition of methyltransferase * Myelosuppression
42
Describe gemcitabine
Gemcitabine * Deoxycytidine analog converts to a triphosphate to inhibit DNA polymerase * Thrombocytopenia and flu-like symptoms
43
Describe cytarabine
Cytarabine * Inhibits DNA polymerase by convertinto ara-cytosine triphosphate * High dose causes neurotoxicity and otoxicity
44
Methotrexate can cause \_\_\_
Methotrexate can cause nephrotoxicity * Nephrotic damage may be irreversible * Requires basic urine to prevent crystallization: give bicarb * Requirements to receive high dose methotraxe: urine pH ≥ 7 until cleared from body
45
\_\_\_ and ___ are topoisomerase I inhibitors
Topotecan and irinotecan are topoisomerase I inhibitors * Camptothecins * Semi-synthetic compounds from plants * Inhibit topoisomerase I: reversible single strand breaks * Myelosuppression and diarrhea
46
Describe diarrhea in irinotecan
Diarrhea in irinotecan 1. Active metabolite SN-38 is inactivated by UGT1A1 (glucuronidation): polymorphism UGT1A1\*2B (reduced enzyme activity) 2. Gut flora deglucuronidates SN38 -\> diarrhea
47
Doxorubicin, daunorubicin, epirubicin, idarubicin, and valrubicin are \_\_\_
Doxorubicin, daunorubicin, epirubicin, idarubicin, and valrubicin are anthracyclines * Intercalate DNA between bases to induce topoisomerase II strand breaks -\> free radicals cause oxidative stress damage * Vesicants * Cardiotoxicity
48
Anthracycline is associated with ___ toxicity
Anthracycline is associated with cardiac toxicity 1. Acute: within first dose or course of treatment 2. Delayed: within 1 year of treatment, dose dependent 3. Late onset: 5-20 yaers, more common in adolescents
49
Topoisomerase II inhibitors consist of ___ and \_\_\_
Topoisomerase II inhibitors consist of anthracenediones and epipodophyllotoxins
50
\_\_\_ is the most common anthracenedione
Bleomycin is the most common anthracenedione * Chelates iron -\> free radical formation * Toxicities: pulmonary fibrosis and interstitial pneumonitis
51
\_\_\_ is a epipodophyllotoxin
Etoposide is a epipodophyllotoxin * Inhibits topoisomerase II: causes primarily single strand and some double strand breaks * Myelosuppression * Secondary leukemia: rearrangement of mixed lineage leukemia at 11q23
52
\_\_\_\_ and ____ are antimicrotubule agents
Taxanes and vinca alkaloids are antimicrotubule agents
53
\_\_\_ and ___ are taxanes
Paclitaxel and docetaxel are taxanes * M phase, inhibit mitotic spindle used in cell division * Stabilize polymerized microtubules against depolymerization * Neurotoxicity and myelosuppression
54
\_\_\_, \_\_\_, and ___ are vinca alkaloids
Vincristine, vinblastine, and vinorelbine are vinca alkaloids * M phase, inhibit mitotic spindle used in cell division * Inhibiti microtubule polymerization by inhibiting mitotic spindle formation * Neurotoxicity * Do NOT give intrathecally * Vesicants
55
Describe chemotherapy classes
Chemotherapy classes
56
Chemotherapy resistance can be \_\_\_, \_\_\_, or \_\_\_
Chemotherapy resistance can be pharmacokinetic, tumor microenvironment, or tumor-cell specific
57
Common chemo toxicities are \_\_\_\_, \_\_\_\_, \_\_\_\_, \_\_\_\_, and \_\_\_\_
Common chemo toxicities are myelosuppression, nausea and vomiting, alopecia, fatigue, and mucositis
58
Describe myelosuppression in chemo toxicity
Myelosuppression in chemo toxicity * Decreased platelets -\> bruising and bleeding * Decreased WBCs -\> risk of infection * Decreased RBCs -\> anemia and fatigue
59
Describe other chemo toxicities
Chemo toxicities
60
Describe long terms effects of chemo
Long-term effects of chemo * Infertility: alkylating agents * Organ dysfunction * Anthracyclines: cardiomyopathy * Topoisomerase II inhibitors: pulmonary fibrosis * Platinums: nephrotixicity * Antimicrotubule agents: neuropathy
61
Describe monoclonal antibodies
Monoclonal antibodies * Targeted antibody: rituximab, nivolumab * Drug conjugates: gemutuzumab * BITE therapy: blinatumomab (fragment antigen binding)
62
Targeted therapies target the ____ pathway and ____ pathway
Targeted therapies target the tyrosine kinase pathway and JAK/STAT pathway
63
Summarize targeted and monoclonal therapy

Heme / Onc (41 decks)

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