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HEME: Yetter > 3.24 SWEATMAN Drug Treatment of Hematologic Malignancies > Flashcards

3.24 SWEATMAN Drug Treatment of Hematologic Malignancies Flashcards

1
Q

Classical Cancer drug administration

A
  • High doses (very toxic; induction therapy)
  • Lower doses (less toxic; consolidation therapy during remission)
  • Maintenance; long term. lower dose therapy during remission
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2
Q

General Rules for Combo Therapy

A
  • Drugs must show activity against the tumor type
  • No two drugs should have the same mechanism of action
  • Drugs should have different patterns of dose-limiting toxicity
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3
Q

Neo-Adjuvant

Adjuvent

A

Neo: before or during surgery/Radiotherapy
Adj: given after surgery/radiotherapy

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4
Q

Metronomic Dosing

A

Daily administration of much lower doses

  • Not all tumors/pts respond
  • Hormesis: treatments designed to kill tumor cells or suppress their proliferation in pts may have the capacity to enhance tumor growths when the drug is present in certain concentrations
  • May avoid pro-proliferative aspect of drug response
  • Thought to avoid the very low drug levels from classic administration suspected to be pro-proliferative (think of anti-biotic levels not high enough and see resistance form, similar concept)
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5
Q

Metronomic Dosing to avoid resistance

A

Gradually decreasing metronomic chemotherapy regimens aim to maintain the equilibrium b/t resitant and non-resistant tumor populations to reserve a certain level of tumor sensitivity leading to life long control rather than complete eradication.

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6
Q

Ways to Stim Anti-Tumor Immune Response

A

-Metronomic chemo with some drugs, by decreasing # and activity of Treg and may promote (re)activation of an anticancer immune response with CTLs and NK cells
Ex Cyclophosphamide

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7
Q

Problems with Metronomic Dosing

A

Nausea, vomitting, anemia, neutropenia, leucopenia and lymphopenia

  • -overall well tolerated
  • Risk in children
  • -angiogenesis important for dev in children
  • Secondary malignancies (all chemo agents)
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8
Q

Leukemia

A
  • Acute: short natural history
  • Chronic: long natural history
  • Myeloid or lymphoid origin
  • AML/ALL(children) or CML./CLL (elderly)
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9
Q

Acute Myeloid Leukemia

A 
Treat with combo of:
DAUNORUBICIN (free rad, intercalate and topo II)
-Tox: BM suppression, CV, Hepatic disease, second malig, extravasational necrosis
Cytarabine, ARA-C (pyrimidine analog)
Tox: BM suppression
THIOGUANINE, 6-TG (purine analog)
-Tox: BM supp 
-Dont always use 6-TG
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10
Q

Post-Remission Therapy

A

More dose-intensive cytarabine-based treatment

-BM allogenic rescue (transplant)

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11
Q

Gemtuzomab (Mylotarg)

A
  • mAb for CD33
  • binds and is internalized, where it has its MOA
  • Shows that mAbs can be used as carries and do not only have to work extracellularly
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12
Q

Acute Promyelocytic Leukemia

A

-PML/RARA fusion drive proliferation
(Retonoic acid receptors alpha)
-All Trans Retinoic Acid (ATRA): leads to differentiation of APL cells and then post-maturation apoptosis
-Tox: Acute Promyelocytic leukemia differentiation syndrome, leukocytosis
-Usually use in combo with other drugs
–anthracycline +/-cytarbine
-Uses ATRA in combo for all stages in different doses

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13
Q

Arsenic Trioxide

A

-Similar action to ATRA but more toxicity on CV system (black box)

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14
Q

Acute Lymphoblastic Leukemia

A
  • Imatinab does not have actions with acute phase, but does work in chronic phase
  • usually use predisone (cortico) +vincristine +antracycline
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15
Q

Imatinib

A

BCR-ABL tyrosine kinase inhibitor, ppl with 9:22 translocation (Philadelphia chromo)

  • usually used with combo therapy
  • regular CBC to monitor cytopenias
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16
Q

Chronic Myeloid Leukemia

A

Imatinib is 1st line of treatment (very effective)

-Dasatinib and Nilotinib are second gen drugs that bind in the ATP pocket with diff orientation than imatinib

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17
Q

Chronic Lymphocytic Leukemia

A

Bendamustine: antimetabolite and alkylating agent
-DNA cross linking and act of p53 pathway
-inhibits check points and forces cell to enter mitosis with damaged DNA leading to mitotic catastrophy
-Less susceptible to cross drug resistance
can also use Alemtuzumab (CD52) and Rituximab (CD20)

18
Q

Hairy Cell Leukemia

A

Use purine analogs: cladribine and Pentostatin

-Can also use IFN-alpha-2b

19
Q

IFN Antineoplastic Action

A

-Direct Antiproliferative effect on tumor cell
-prolong all phases of cell cycle and induce cellular differentiation
Induce host responses
-Activate Cytotoxic T cells and/or NK cells and other phagocytes

20
Q

Lymphomas

A

Hodgkin and non-Hodgkin Lymphomas

21
Q

Hodgkin Lymphomas

A
  • Use a lot of combinations, all drug combos have drugs with different MOAs, leads to decreased cross reactivity and decreased general drug toxicity
  • Common combos: contain anthracycline (doxorubicin), mitotic spindle inhibitor (vincristine) and alkylating agents (cyclo or bleomycin), a carbazine and sometime a corticosteroid
22
Q

Bleomycin (toxicity)

A

Idiosyncratic rxn to bleomycin (fever), pulmonary fibrosis

23
Q

Busulfan

A

BM suppression, secondary malignancies

24
Q

Carboplatin

A

anemia, infection

25
Q

Chlorambucil

A

BM suppression, secondary malignancy, pregnancy, infertility

26
Q

Cladribine

A

BM suppression neurotoxicity

27
Q

Ifosfamide

A

Coma, hemorrhagic cystitis

28
Q

Dacarbazine

A

BM suppression, hepatic disease, pregnancy, secondary malignancy

29
Q

Daunorubicin, Doxorubicin, and Idarubicin

A

BM suppression, heart disease, hepatic disease, secondary malignancy, extravasational necrosis

30
Q

Etoposide

A

Myelosuppression, bleeding, oppurtunistic Infection

31
Q

Teniposide

A

BM suppression

32
Q

Fludarabine

A

BM suprression, coma, seizures, dont give with pentostatin

33
Q

INF-alpha-2b

A

Contraindicated with autoimmune disease, cardiac disease, increased suicidal ideation, depression

34
Q

Mechlorethamine

A

BM suppression, extravasation, pregnancy

35
Q

Methotrexate

A

Ascites, diarrhea, exfoliative dermatitis, infection, lymphoma, pulmonary disease, pulmonary fibrosis, renal impairment, stomatitis, tumor lysis syndrome (TLS)

36
Q

Mitoxantrone

A

Extravasation, HR failure, intrahecal administration, neutropenia, secondary malignancy

37
Q

Pentostatin

A

Hepatic disease, pulmonary edema, renal failure, seizures, use with fludarabine

38
Q

Vinblastine, Vincristine

A

Extravasation, intrahecal administration-FATAL, neuropathic toxicity

39
Q

Alemtuzumab

A

BM suppression, infection, infusion rxn

40
Q

Gemtuzumab, Ozogamicin

A

BM suppression, hepatic and pulmonary disease, infusion rxn

HEME: Yetter (22 decks)

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