B.37. Cancer chemotherapy VI (large molecule signal transduction inhibitors)

Question 1

list the signal transduction inhibitors (large molecules)

Answer 1

Trastuzumab 
Panitumumab 
Rituximab 
Bevacizumab 
Pembrolizumab 
IFN- 𝝰
Aldesleukin

Question 2

what is Trastuzumab?

Answer 2

-anti-HER2/neu receptor
(epidermal growth factor receptor)
-Humanized monoclonal Ab

Question 3

which Ab are humanized monoclonal Ab?

Answer 3

trastuzumab
Bevacizumab
Pembrolizumab

Question 4

which Ab is a chimeric monoclonal Ab?

Answer 4

Rituximab

Question 5

which Ab is a human monoclonal Ab?

Answer 5

Panitumumab

Question 6

what is Trastuzumab-emtansine?

Answer 6

Antibody-drug conjugate:

trastuzumab covalently linked to the cytotoxic agent emtansine (DM1)

Question 7

what does emtansine do?

Answer 7

binds tubulin and cause mitotic arrest–> cell death

Question 8

indications for Trastuzumab (+emtansine)

Answer 8

breast cancer (HER2 +)

Question 9

side effects of Trastuzumab

Answer 9

injection-site reaction
nausea, vomiting
cardiotoxicity (reduced EF, CHF)

Question 10

what is Panitumumab and Cetuximab?

Answer 10

anti-EGFR

human monoclonal Ab

Question 11

what is the indication of Panitumumab?

Answer 11

colon cancer (metastatic disease, K-RAS wild type)

Question 12

what tumors are resistant to Panitumumab?

Answer 12

mutated K-RAS tumors

Question 13

side effects of Panitumumab

Answer 13

dermatologic symptoms
nausea, vomiting
diarrhea

Question 14

which agents do we give in combination with Panitumumab?

Answer 14

Irinotecan
fluorouracil
leucovorin
(FOLFIRI protocol)

Question 15

what is Rituximab?

Answer 15

Anti-CD20 (expressed on B-cells)

chimeric monoclonal Ab

Question 16

what is the mechanism of Rituximab?

Answer 16

binding on B cells–> induces complement-mediated lysis–> direct cytotoxicity and induction of apoptosis–> B- cell count ↓

Question 17

indications of Rituximab

Answer 17

Non-Hodgkin's B cell lymphoma 
CLL
post-transplant lymphoma 
immune-mediated diseases (RA, AIHA,ITP, TTP)
Wegner granulomatosis

Question 18

side effects of Rituximab

Answer 18

1. hypersensitivity reaction
   * infusion reaction
   * serum sickness
2. tumor lysis syndrome
3. myelosuppression
4. risk of latent infections (JC virus, HBV)

Question 19

what is Bevacizumab?

Answer 19

anti-VEGF (anti-angiogenesis agent)

humanized monoclonal Ab

Question 20

indications for Bevacizumab?

Answer 20

colon cancer
breast cancer
non-small lung carcinoma
renal cancer

Question 21

Side effects of Bevacizumab

Answer 21

hypertension 
impaired wound healing
injection site reaction
arterial thromboembolism
Gi perforation (rare)

Question 22

What is Pembrolizumab?

Answer 22

1. immunomodulator (check-point protein modulator)
2. Antibody binds PD-1 Receptor of lymphocytes (programmed cell death protein 1)–> blocks T cell activation
3. Humanized monoclonal Ab (IgG₄ isotype)

Question 23

when do we give Pembrolizumab?

Answer 23

melanoma

non-small cell lung carcinoma

Question 24

side effects of Pembrolizumab?

Answer 24

injection site reaction
pneumonitis
inflammation of endocrine glands

Question 25

what is IFN-𝝰?

Answer 25

cytokine with antineoplastic, antiviral, immunosuppressive properties

Question 26

what does IFN-𝝰 do?

Answer 26

binds to a specific receptor on the cell membrane
induces gene transcription
inhibits cellular growth
very cytotoxic–> cell death

Question 27

when do we use IFN-𝝰?

Answer 27

CLL 
Hairy-cell leukemia 
T-cell lymphomas
AIDS-related Kaposi sarcoma 
HPV, HBV, HCV

Question 28

Side effects of IFN-𝝰

Answer 28

Flu-like symptoms
myelosuppression
neurotoxicity
Fever, alopecia

*damage to all organs

Question 29

what is Aldesleukin?

Answer 29

IL-2 recombinant protein

stimulates growth and differentiation of T, B, NK Cells

Question 30

when do we give Aldesleukin?

Answer 30

Renal cancer

Melanoma

Question 31

side effects of Aldesleikin

Answer 31

Diarrhea
hypotension
capillary leak syndrome (CLS)