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Heme / Onc > SM_276b: Chemotherapy Basics > Flashcards

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
Q

___ and ___ are cell cycle nonspecific chemotherapeutic agents

A

Alkylating agents and anthracyclines are cell cycle nonspecific chemotherapeutic agents

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26
Q

Describe types of alkylating agents

A

Alkylating agents

27
Q

Describe alkylating agents

A

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
Q

Describe alkylating agent toxicities

A

Alkylating agent toxicities

  • Alkyl sulfonates (busulfan): pulmonary toxicity
  • Nitrogen mustards (cyclophosphamide, ifosfamide): pro-drugs, hemorrhagic cystitis
  • Nitrosureas (carmustine, lomustine): pulmonary fibrosis
29
Q

Platinum alkylating agents are ___, ___, and ___

A

Platinum alkylating agents are cisplatin, carboplatin, and oxaliplatin

Metal adducts that cross-link DNA

30
Q

Carboplatin has toxicity of ____

A

Carboplatin has toxicity of thrombocytopenia (myelosuppression)

31
Q

Oxaliplatin toxicity is ___

A

Oxaliplatin toxicity is neurotoxicity (cold sensitivity, peripheral neuropathy)

32
Q

Cisplatin toxicities are ____ and ____

A

Cisplatin toxicities are nephrotoxicity and delayed CINV

33
Q

Alkyl sulfonates (busulfan) have toxicity of ___

A

Alkyl sulfonates (busulfan) have toxicity of pulmonary toxicity

34
Q

Nitrogen mustards (cyclophosphamide, ifosfamide) are ___ and have toxicity of ___

A

Nitrogen mustards (cyclophosphamide, ifosfamide) are pro-drugs and have toxicity of hemorrhagic cystitis

35
Q

Nitrosureas (carmustine, lomustine) have toxicity of ___

A

Nitrosureas (carmustine, lomustine) have toxicity of pulmonary fibrosis

36
Q

Describe types of antimetabolites

A

Antimetabolites

37
Q

Describe antimetabolites

A

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
Q

Purine antagonists (mercaptopurine and thioguianine) ___ and are ___

A

Purine antagonists (mercaptopurine and thioguianine) inhibit de novo purine synthesis and are metabolized by thiopurine methyltransferase

  • Thiopurine methyltransferase has polymorphisms
39
Q

Purine analogs (cladribine, fludarabine, clofarabine, and pentostatin) ____

A

Purine analogs (cladribine, fludarabine, clofarabine, and pentostatin) mimic deoxyadenosine

  • Myelosuppression
40
Q

Pyrimidine analogs (capecitabine, fluorouracil, gemcitabine, cyarabine, azacytidine, and decitabine) mimic ___

A

Pyrimidine analogs (capecitabine, fluorouracil, gemcitabine, cyarabine, azacytidine, and decitabine) mimic pyrimidines

  • Capacitabine and fluorouracil lead to hand foot syndrome, mucositis, and diarrhea
41
Q

Describe azacitidine and decitabine

A

Azacitidine and decitabine

  • Hypomethylation of DNA by inhibition of methyltransferase
  • Myelosuppression
42
Q

Describe gemcitabine

A

Gemcitabine

  • Deoxycytidine analog converts to a triphosphate to inhibit DNA polymerase
  • Thrombocytopenia and flu-like symptoms
43
Q

Describe cytarabine

A

Cytarabine

  • Inhibits DNA polymerase by convertinto ara-cytosine triphosphate
  • High dose causes neurotoxicity and otoxicity
44
Q

Methotrexate can cause ___

A

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
Q

___ and ___ are topoisomerase I inhibitors

A

Topotecan and irinotecan are topoisomerase I inhibitors

  • Camptothecins
  • Semi-synthetic compounds from plants
  • Inhibit topoisomerase I: reversible single strand breaks
  • Myelosuppression and diarrhea
46
Q

Describe diarrhea in irinotecan

A

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
Q

Doxorubicin, daunorubicin, epirubicin, idarubicin, and valrubicin are ___

A

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
Q

Anthracycline is associated with ___ toxicity

A

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
Q

Topoisomerase II inhibitors consist of ___ and ___

A

Topoisomerase II inhibitors consist of anthracenediones and epipodophyllotoxins

50
Q

___ is the most common anthracenedione

A

Bleomycin is the most common anthracenedione

  • Chelates iron -> free radical formation
  • Toxicities: pulmonary fibrosis and interstitial pneumonitis
51
Q

___ is a epipodophyllotoxin

A

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
Q

____ and ____ are antimicrotubule agents

A

Taxanes and vinca alkaloids are antimicrotubule agents

53
Q

___ and ___ are taxanes

A

Paclitaxel and docetaxel are taxanes

  • M phase, inhibit mitotic spindle used in cell division
  • Stabilize polymerized microtubules against depolymerization
  • Neurotoxicity and myelosuppression
54
Q

___, ___, and ___ are vinca alkaloids

A

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
Q

Describe chemotherapy classes

A

Chemotherapy classes

56
Q

Chemotherapy resistance can be ___, ___, or ___

A

Chemotherapy resistance can be pharmacokinetic, tumor microenvironment, or tumor-cell specific

57
Q

Common chemo toxicities are ____, ____, ____, ____, and ____

A

Common chemo toxicities are myelosuppression, nausea and vomiting, alopecia, fatigue, and mucositis

58
Q

Describe myelosuppression in chemo toxicity

A

Myelosuppression in chemo toxicity

  • Decreased platelets -> bruising and bleeding
  • Decreased WBCs -> risk of infection
  • Decreased RBCs -> anemia and fatigue
59
Q

Describe other chemo toxicities

A

Chemo toxicities

60
Q

Describe long terms effects of chemo

A

Long-term effects of chemo

  • Infertility: alkylating agents
  • Organ dysfunction
    • Anthracyclines: cardiomyopathy
    • Topoisomerase II inhibitors: pulmonary fibrosis
    • Platinums: nephrotixicity
    • Antimicrotubule agents: neuropathy
61
Q

Describe monoclonal antibodies

A

Monoclonal antibodies

  • Targeted antibody: rituximab, nivolumab
  • Drug conjugates: gemutuzumab
  • BITE therapy: blinatumomab (fragment antigen binding)
62
Q

Targeted therapies target the ____ pathway and ____ pathway

A

Targeted therapies target the tyrosine kinase pathway and JAK/STAT pathway

63
Q

Summarize targeted and monoclonal therapy

A

Heme / Onc (41 decks)

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