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Blood and Lymph_pharm_misc > Tx of Leukemias and Lymphomas > Flashcards

Tx of Leukemias and Lymphomas Flashcards

1
Q

Contrast adjuvant Tx w/ neo-adjuvant Tx

A

adjuvant–chemo following surgery or radiation

neoadjuvant–chemo BEFORE surgery or radiation

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2
Q

Cell-Cycle Specific (CSS) chemo drug classes [3]

A
  1. antimetabolites
  2. topoisomerase inhibitors
  3. microtubule poisons
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3
Q

Cell-Cycle non-specific (CCNS) chemo drug classes [2]

A
  1. alkylating agents

2. anti-tumor antibiotics

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4
Q 
Cyclophosphamide
Route:
MOA:
AE:
*
A 
Route: oral or IV
MOA: N-mustard pro-drug; activated by host metabolism (liver)
-Alkylating Agent
AE:
-nausea/vomiting
-myelosuppression (dose-related)
-alopecia
-sterile hemorrhagic cystitis

*CPH is cleaved into activated particles which are toxic to bladder epithelial cells

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5
Q 
Mechlorethamine
Route:
MOA:
AE:
*Tx:
T 1/2:
A

Route: IV only (caustic to skin/mucous membranes–causes necrosis)
MOA: N-mustard; Alkylating Agent
AE:
-nausea/vomiting
-decreased blood counts; minimal count 10-12 days after Tx; recovery 3-6 wks

  • Tx:Hodgkin’s Lymphoma (MOPP Tx)
  • T 1/2: MINUTES
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6
Q 
Melphalan
Route:
MOA:
AE:
T 1/2:
Tx:
A

Route: IV
MOA: phenylalanine N-mustard; Alkylating Agent
AE: myelosuppression
T 1/2: 50 minutes

  • renal excretion
  • Tx: Multiple Myeloma; myeloablative therapy
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7
Q 
Bendamustine
Route:
MOA:
AE:
T 1/2:
Tx:
A 
Route: IV
MOA: N-mustard; Alkylating Agent
AE: 
-nausea/vomiting
-myelosuppression
-mucositis
T 1/2: 30 minutes
Tx: CLL; indolent B-cell Non-Hodgkins lymphoma
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8
Q 
Chlorambucil
Route:
MOA:
AE: ?
T 1/2:
Tx:
A 
Route: ORAL
MOA: N-mustard; Alkylating Agent
AE: ?
T 1/2: 1.5 hrs
Tx: CLL (now rarely used)
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9
Q 
Busulfan
Route:
MOA:
AE:
T 1/2: ?
Tx:
A 
Route: ORAL or IV (high doses)
MOA: Alkylsulfonate: Alkylating Agent
AE:
-profound myelosuppression
-pulm fibrosis
-veno-occlusive dx
T 1/2: ?
Tx: CML (prior to Imatinib)
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10
Q 
Decarbazine
Route:
MOA:
AE:
T 1/2:
Tx:
A

Route: IV
MOA: activated by hepatic metabolism; Alkylating Agent
AE: acute nausea/vomiting; delayed myelosuppression (dose-limiting)
T 1/2:
Tx: Hodgkin’s lymphoma; multiple myeloma

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11
Q

Anticancer metabolites [3]

A
  1. folate analogs
  2. purine analogs
  3. pyrimidine analogs

*enters and interrupts a normal metabolic pathway

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12
Q

Drug which may be “rescued” with folinic acid (Citrovorin, leucovorin)

A

Methotrexate

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13
Q 
Methotrexate
Route:
MOA:
AE:
Resistance:
A

Route: oral, IV, intrathecal
MOA: Dihydrofolate reductase (DHFR) inhibitor; Anti-Metabolite
AE:
-anti-folate AE (bone marrow, GI)
-hepatotoxicity (chronic use)
T 1/2:
Resistance: decreased drug accumulation, amplified DHFR, altered DHFR

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14
Q 
6-Mercaptopurine, 6-Thioguanine
Route:
MOA:
AE:
Resistance:
A

Route: Oral
MOA: purine analogs; Anti-Metabolites
AE: well-tolerated, bone marrow suppression at high doses
Resistance: decrease in hprt activity, increase in alkaline phosphatase

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15
Q 
Fludarabine
Route:
MOA:
AE:
T 1/2:
Tx:
A

Route: oral, IV (monophosphate)
MOA: purine analog; Anti-Metabolite
-diphosphate–inhibits ribonucleotide reductase
–triphosphate–inhibits DNA polymerase and ligase, incorporated into RNA and DNA
AE: nausea/vomiting, myelosuppression
T 1/2:
Tx: mono- or combo Tx for CLL

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16
Q 
Cytarabine
Route:
MOA:
AE:
Tx:
A

Route: IV, intrathecal
MOA: pyrimidine analogs; Anti-Metabolite
-activated by deoxycytidine kinase–polymorphic
–triphosphate incorporated into DNA, inhibits elongation/repair
AE: more toxic than purines, myelosuppression, GI, stomatitis
Tx: AML, ALL

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17
Q 
Vinblastine
Route:
MOA:
AE:
*
A

Route: IV
MOA: inhibits/reverses tubulin polymerization, disrupts mitotic spindles
-metaphase arrest
-plant alkaloid
AE: nausea/vomiting, alopacia, Bone marrow depression
*biliary excretion

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18
Q

Vincristine (Oncovin)
Route:
MOA:
AE:

A

Route: IV
MOA: inhibits/reverses tubulin polymerization, disrupts mitotic spindles
-metaphase arrest
-plant alkaloid
AE: short duration due to peripheral neuropathy
-less toxic to bone marrow, no nausea/vomiting

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19
Q

Etoposide (VP-16)
Route:
MOA:
AE:

A

Route: oral, IV
MOA: topoisomerase-II inhibitor (dsDNA breaks)
-CCS
-arrests cells in S-G2 stage
-podophyllotoxin
-plant alkaloid
AE: nausea/vomiting, alopecia, bone marrow suppression

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20
Q

Route of all anti-tumor antibiotics

21
Q 
Doxorubicin
Route:
MOA:
AE:
Tx:
A 
Route: IV
MOA: intercalate into DNA
-block topoisomerase-II
-strand breaks
-antitumor antibiotic; anthracycline
AE: bone marrow suppression, GI, alopecia, CARDIOTOXICITY (function of cumulative dose)
  • free radical mechanism
    • -minimize by admin of Dexrazoxane
22
Q 
Daunorubicin
Route:
MOA:
AE:
Tx:
A 
Route: IV
MOA: intercalate into DNA
-block topoisomerase-II
-strand breaks
-antitumor antibiotic; anthracycline
AE: bone marrow suppression, GI, alopecia, CARDIOTOXICITY (function of cumulative dose)
  • free radical mechanism
    • -minimize by admin of Dexrazoxane
23
Q 
Idarubicin
Route:
MOA:
AE:
Tx:
A 
Route: IV
MOA: intercalate into DNA
-block topoisomerase-II
-strand breaks
-antitumor antibiotic; anthracycline
AE: bone marrow suppression, GI, alopecia, less cardiotoxic
  • free radical mechanism
    • -minimize by admin of Dexrazoxane
24
Q 
Bleomycin
Route:
MOA:
AE:
Tx:
A 
Route: IV
MOA: binds DNA, generates ROS
-causes strand breaks
--active in G2 (CSS)
anti-tumor antibiotic
AE: 
-hypersensitivity, cutaneous rxns
-pulm toxicity
-fibrosis
Tx:
25
Q 
Dexamethasone, Prednisone
Route:
MOA:
AE:
Tx:
A

Route: oral
MOA: suppresses proliferation of immune cells (growth/differation of many tissues is under hormonal control)
AE: fluid retention, immunosuppression, diabetes
Tx: leukemias, lymohomas

26
Q 
Asparaginase
Route:
MOA:
AE:
Tx:
A

Route: ?
MOA: catalyzes breakdown of asparagine in blood, inhibits growth of ALL cells, which lack asparagine synthetase
AE: allergic responses, enhances coagulation
Tx: ALL

27
Q 
Rituxamab
Route:
MOA:
AE:
T 1/2:
Tx:
A

Route: IV
MOA: monoclonal Ab, blocks CD20 B-cell Ag
AE: allergic reactions, hypogammaglobulinemia, autoimmune disorders
T 1/2: 22 days
Tx: B-cell lymphomas–CLL, Non-Hodgkin’s

28
Q 
Imatinib (gleevec)
Route:
MOA:
AE:
Tx:
A

Route: ?
MOA: inhibits bcr-abl and c-kit tyrosine kinase
-signal transduction inhibitor targeted therapy
AE: myelosuppressive, fluid retention, hepatotoxicity
Tx: CML (blocks growth factor signaling)
-used in any hematologic malignancy w/ Philadelphia chromosome

29
Q

Dasatinib, Nilotinib
Route:
MOA:

A

Route: ?
MOA: newer tyrosine kinase inhibitors, broader spectrum than Imatinib

  • STI (signal transduction inhibitor) transforms cancer from “curable” to “managable”
  • STI Tx continues until 1. tumor gains resistance, 2. patient dies, 3. pt chooses to discontinue drug
30
Q 
Ibrutinib
Route:
MOA:
AE:
Tx:

*CYP

A

Route: oral
MOA: inhibits Bruton’s tyrosine kinase (BTK)
-signal transduction inhibitor
AE: GI, thrombocytopenia, neutropenia, infections, fatigue
Tx: mantle cell lymphoma, relapsed CLL (esp w/ 17p deletion)

*CYP3A4–15x more potent as BTK inhibitor

31
Q 
Idelalisib
Route:
MOA:
AE:
Tx:

*CYP

A

Route: oral
MOA: P13K inhibitor
-signal transduction inhibitor
AE: potentiall fatal HEPATOTOXICITY, diarrhea/colitis, pneumonitis, intestinal perforation
Tx: relapsed CLL, SLL, follicular B-ell, Non-Hodgkin’s

  • CYP3A4 inhibitor
  • metabolized by CYP3A4 and aldehyde oxidase
32
Q 
all-trans-Retinoic acid (ATRA triretinoin)
Route:
MOA:
Tx:
Resistance: *CYP
A

Route: ?
MOA: binds retinoic-acid receptor-gamma, promotes cell differentiation
-“differentiating agent”
-promotes degredation of PML-RAR-alpha fusion protein
-activates RAR-gamma
Tx: mono-therapy or w/ anthracycline or arsenic for APL
Resistance: through enhanced clearance (CYP26A1) or loss of fusion gene expression

33
Q

Arsenic trioxide

MOA:

A
  • differentiating agent
  • inhibits thioredoxin reductase–enhancing oxidative stress
  • promotes modification /degredation of APL fusion protein
  • cytotoxic, and promotes differentiation
34
Q 
Lenalidomide
MOA:
AE:
Tx:
*
A

MOA: differentiating agent
-thalidomide derivative
AE: lacks teratogenic, sedative effects of thalidomide
Tx: CLL, multiple myeloma

*may inhibit effects of Rituximab

35
Q

Combination Chemotherapy regiments

ABVD

A

Adriamycin (doxorubicin)
Bleomycin
VinBlastine
Decarbazine

36
Q

Combination Chemotherapy regiments

CHOP

A 
Cyclophosphamide
Doxorubicin
Oncovin (Vincristine)
Prednisone
*add rituximab R-CHOP
37
Q

Combination Chemotherapy regiments

COP or CVP

A

Cyclophosphamide
Oncovin (Vincristine)
Prednisone
*add rituximab R-COP

38
Q

Combination Chemotherapy regiments

MOPP

A

Mechlorethamine
Oncovin (Vincristine)
Procarbazine
Prednisone

39
Q

Combination Chemotherapy regiments

Hyper-CVAD

A 
Cyclophosphamide
Doxorubicin
Vincristine
Dexamethasone
Methotrexate
Cytarabine
Prednisone
40
Q

Combination Chemotherapy regiments

Stanford V

A 
Doxorubicin
VinBlastine
Bleomycin
N-mustard
Prednisone
Etoposide
41
Q

Tx of Acute Lymphocytic Leukemia (ALL)

A

Asparaginase
Dasatinib - if t(9;22) +
Rituximab - if CD 20+
6-Mercaptopurine

*Hyper - CVAD Combo:
Cyclophosphamide
Doxorubicin
Vincristine
Dexamethasone
Methotrexate
Cytarabine
Prednisone
42
Q

Tx of Acute Myelocytic Leukemia (AML)

A

Cytarabine
Idarubicin

*“3+7” regimen (idarubicin daily infusion, days 1-3; cytarabine continuous infusion days 1-7)

43
Q

Tx of Acute Promyelocytic Leukemia (APL)

A

ATRA
Daunorubicin/Idarubicin
Arsenic trioxide - if High-risk

44
Q

Tx of Chronic Lymphocytic Leukemia (CLL)

A
  • Watch and wait if no symptoms
  • Chlorambucil and Predisone
  • Fludarabine and Rituximab
  • Bendamustine and Rituximab
  • Fludarabine, Rituximab and Cyclophosphamide
  • COP
  • CHOP
  • R-COP
  • R-CHOP
  • Lenalomide - Refractory cases
45
Q

Tx of Chronic Myelocytic Leukemia (CML)

A

Imatinib

Dasatinib/Nilotinib - if resistant

46
Q

Tx of Non-Hodgkin’s Lymphoma

A

Rituximab
Rituximab plus Fludarabine or Bendamustine
R-COP
R-CHOP
May combine with involved field radiation

47
Q

Tx of Diffuse Large B-Cell Lymphoma

A

R-CHOP

Clinical trials

48
Q

Tx of Hodgkin’s Lymphoma

A

MOPP - used to be mainstay of treatment
ABVD - more effective, better tolerated than MOPP
R-CHOP and Stanford V for advanced disease

*Increasingly aggressive chemo and radiation for more advanced disease

Blood and Lymph_pharm_misc (4 decks)

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