General Week 4 (CLL, Cancer Drugs)

Question 1

IL-12

Answer 1

induces IFNgamma –> increases inducible protein 10, which is anti-angiogenic

fever, chills, GI effects, liver function effects –> but decreases with time

Question 2

IFNalpha

Answer 2

decreases cell devision and increases MHC I

decreases FGF

Question 3

Bevacizumab

Answer 3

anti-VEGF (not VEGF-R)

Also used for diabetic retinopathy and macular degeneration [Ranibizumab]

common toxicities + GI perforation, wound deshisence, hemoptisis (spitting of blood, this can be fatal)–> risk with coronary heart disease

Question 4

Pazopanib, Sorafinib, Sunitinib

Answer 4

VEGF-R and PGF-R (orally, CYP 3A4, renal cell carcinoma)

Less specific than imatinib
Sorafinib = Raf
Pazo and Suni = c-Kit

congestive heart failure, but less than imatinib
teratogenic, PAZO and SOR= hepatotox, GI perforation, hypertension
Sunitinib = hand foot syndrome, skin color change.

Question 5

Everolimus, Temsirolimus

Answer 5

mTOR inhib (oral for renal cell carcinoma) –> decrease cell growth and proliferation via mTOR, which regulates cyclin D1 (G1/S) also, has bioenergetic activity

Decrease VEGF and PDGF release from cancer cells

Increases cytotoxicity with drugs that damage DNA

Tox: hypersensitivity, immunosuppression, angioedema, kidney thrombosis, delays in wound healing, nephrotoxicity, male infertility, hyperlipidemia

Question 6

Thalidomide

Answer 6

(oral) hanson’s disease (suppresses immune system –> lessening sump) and multiple myeloma (+ dexamethosone –> remission in 80%)
teratogenic –> results in phocomelia, effects occur 3-4 weeks post conception, and children/grandchildren affected

shifts CD4+ Th1 to Th2

*most potent antineoplastic TNFalpha agent
antiangiogenic

Tox: few side effects (besides teratogenic), peripheral neuropathy, increased risk for DVT (use warfarin)

Question 7

pulse therapy

Answer 7

intermittent high doses in cycles to allow recovery (primarily for bone marrow)

Question 8

rescue therapy

Answer 8

give high dose and then give antidote to rescue normal cells

Question 9

combination therapy

Answer 9

select drugs that

1. are effective alone
2. different MOA and mechanisms of resistance
3. CCNS/CCS
4. different toxicities

synergistic? hopefully…. could also decrease dose and decrease toxicity.

decrease development of resistance and clonal selection

Question 10

recruitment

Answer 10

CCNS given 1st –> recruits cells out of G0 –> then give CCS drug

example breast cancer regimen = cyclophosphamide (CCNS), methotrexate and 5-FU (CCS)

Question 11

synchrony

Answer 11

use CCS drugs to synchronize cell division –> increase sensitivity for radiation (ex. hydroxyurea + radiation)

Question 12

Hodgkin’s Lymphoma

Answer 12

malignant cell is Reed-Sternberg cell (req. for diagnosis) - CD15+, CD30+

B-cell (some are CD20+)

node to node spread

ABVD Tx (adriamycin, bleomycine, vinblastine, dacarbazine) + Rituximab

Question 13

How do you diagnose lymphoma?

Answer 13

Excisional biopsy (also bone marrow and flow)

CBC with diff. + CMP + LDH + uric acid

staging imaging (CT/PET)

hepatitis B, HIV screen

Question 14

Stage I lymphoma

Answer 14

single lymph node region or single organ

Question 15

Stage II lymphoma

Answer 15

two or more lymph node regions on same side of the diaphragm

Question 16

Stage III lymphoma

Answer 16

tow (or more) lymph node regions above and below the diaphragm

Question 17

Stage IV lymphoma

Answer 17

multiple organ with or without lymph node involvement (spleen and thymus don’t count)

Question 18

What is the late effect of bleomycin containing regimens for lymphoma?

Answer 18

lung disease = acute interstitial pneumonitis

Question 19

CD5-, CD19+, CD20+, CD23+, marrow negative, increased LDH…

Answer 19

diffuse large B-cell lymphoma DLBCL

Question 20

DLBCL Pearls….

Answer 20

most common NHL in adults

treated with CHOP + rituximab (R-CHOP)

Question 21

CD10+, CD20+, CD5-, CD23-, BCL6+

Answer 21

Follicular Lymphoma
t(14,18) –> BCL (18q) + IgH (14q) chain
over-expression of BCL-2 (anti-apoptosis)
not curable with chemo

Question 22

CD20+, CD5+, Cyclin D1 +,

Answer 22

mantel cell lymphoma t(11;14)

Tx = 6 cycles of R-CHOP

Question 23

CD19+, CD20+ (dim), CD23+, CD5+

monoclonal lymphocyte count >10,000

Answer 23

CLL (impt = monoclonal –> kappa or lambda (not both))

Question 24

Does every CLL patient need treatment?

Answer 24

No.

There is no survival benefit with early treatment of low risk patients –> early stage disease is just followed

Question 25

CD20+, CD10-, CD5-, CD23-

Answer 25

Malt Lymphoma

If stomach = H. Pylori

Question 26

Solid organ transplant patients (or other patients with immune suppression) should make you think of…

Answer 26

PTLPD (post transplant lymphoproliferative disorder)

This is EBV caused! Why? Suppression of T-cells –> loss of suppression of B-cell proliferation –> polyclonal B-cell expansion

Tx: back off immune suppression