3.24 SWEATMAN Drug Treatment of Hematologic Malignancies Flashcards Preview

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Flashcards in 3.24 SWEATMAN Drug Treatment of Hematologic Malignancies Deck (40):
1

Classical Cancer drug administration

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

2

General Rules for Combo Therapy

-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

3

Neo-Adjuvant
Adjuvent

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

4

Metronomic Dosing

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)

5

Metronomic Dosing to avoid resistance

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.

6

Ways to Stim Anti-Tumor Immune Response

-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

7

Problems with Metronomic Dosing

Nausea, vomitting, anemia, neutropenia, leucopenia and lymphopenia
--overall well tolerated
-Risk in children
--angiogenesis important for dev in children
-Secondary malignancies (all chemo agents)

8

Leukemia

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

9

Acute Myeloid Leukemia

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

10

Post-Remission Therapy

More dose-intensive cytarabine-based treatment
-BM allogenic rescue (transplant)

11

Gemtuzomab (Mylotarg)

-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

12

Acute Promyelocytic Leukemia

-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

13

Arsenic Trioxide

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

14

Acute Lymphoblastic Leukemia

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

15

Imatinib

BCR-ABL tyrosine kinase inhibitor, ppl with 9:22 translocation (Philadelphia chromo)
-usually used with combo therapy
-regular CBC to monitor cytopenias

16

Chronic Myeloid Leukemia

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

17

Chronic Lymphocytic Leukemia

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

Hairy Cell Leukemia

Use purine analogs: cladribine and Pentostatin
-Can also use IFN-alpha-2b

19

IFN Antineoplastic Action

-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

Lymphomas

Hodgkin and non-Hodgkin Lymphomas

21

Hodgkin Lymphomas

-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

Bleomycin (toxicity)

Idiosyncratic rxn to bleomycin (fever), pulmonary fibrosis

23

Busulfan

BM suppression, secondary malignancies

24

Carboplatin

anemia, infection

25

Chlorambucil

BM suppression, secondary malignancy, pregnancy, infertility

26

Cladribine

BM suppression neurotoxicity

27

Ifosfamide

Coma, hemorrhagic cystitis

28

Dacarbazine

BM suppression, hepatic disease, pregnancy, secondary malignancy

29

Daunorubicin, Doxorubicin, and Idarubicin

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

30

Etoposide

Myelosuppression, bleeding, oppurtunistic Infection

31

Teniposide

BM suppression

32

Fludarabine

BM suprression, coma, seizures, dont give with pentostatin

33

INF-alpha-2b

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

34

Mechlorethamine

BM suppression, extravasation, pregnancy

35

Methotrexate

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

36

Mitoxantrone

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

37

Pentostatin

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

38

Vinblastine, Vincristine

Extravasation, intrahecal administration-FATAL, neuropathic toxicity

39

Alemtuzumab

BM suppression, infection, infusion rxn

40

Gemtuzumab, Ozogamicin

BM suppression, hepatic and pulmonary disease, infusion rxn