CHAPTER 28

PHARMACOLOGY AND TOXICITY

OF ANTINEOPLASTIC DRUGS
1. DOSE MODIFICATION: A. HEPATIC B.
RENAL

i. Doxorubicin A
ii. Etoposide B
iii. Vincristine A
iv. PonatinibA
v. Imatinib B
vi. Lenalidomide B
vii. Hydroxyurea B
viii. Methotrexate B
2. The toxicity of radiation therapy to normal tissues such as skin, lung,
heart, and brain is markedly enhanced by concurrent administration of the
following medications EXCEPT:
A. Anthracyclines
B. Bleomycin
C. 5-fluorouracil
D. Gemcitabine

• Thus, 5-fluorouracil and cisplatin are potent radiosensitizers and are often used with
radiation therapy to improve local tumor control of the head and neck and
gastrointestinal cancers.

• The toxicity of radiation therapy to normal tissues such as skin, lung, heart, and brain is
markedly enhanced by concurrent administration of anthracyclines, bleomycin, or
gemcitabine.
3. Cells are most vulnerable to cell-cycle-specific agents at what stage
of their life cycle

A. G1
B. S Phase
C. G2
D. Mitosis
E. G0
4. TRUE OR FALSE | Methotrexate

A. Patients receiving HD-MTX can be rescued from drug toxicity by administering small doses
of N-10-formyltetrahydrofolate (leucovorin). It is administered intravenously or orally in
doses of 10–25 mg/m2 at 12-hour 6- hour intervals, starting 6–24 hours after the infusion
of MTX, and continues until plasma levels fall below 2 1 μM. FALSE

B. MTX and its hydroxylated metabolite are organic acids and, have limited solubility at acid
pH. Hence, to prevent renal dysfunction, we do pretreatment hydration of 1.5 2.5 L/24 h
during drug infusion and by raising the urine pH higher than 8 7 with intravenous sodium
bicarbonate prior to and during therapy. FALSE

C. Toxic doses suppress all marrow components, although anemia leukopenia is more
common. FALSE

D. Transaminase elevations rapidly return to normal in most patients, and without sequelae,
although low-dose chronic administration, used to treat psoriasis or rheumatoid arthritis,
may lead to cirrhosis. TRUE
5. TRUE OR FALSE | Cytarabine

A. Ara-C confers particular benefit in patients with cytogenetic abnormalities (t[8:21], inv[16],
t[9:16], and del[16]) related to the core binding factor that regulates hematopoiesis. TRUE

B. The nadir of the white count and platelet count occurs at about days 10 to 14 7-10 days
after the last dose of drug. FALSE

C. In patients older than 60 years, and in patients with renal dysfunction, intravenous high-dose
ara-C (3 g/m2 every 12 hours, days 1, 3, and 5, for 6 doses) causes a high incidence of
cerebellar toxicity, manifested as ataxia and slurred speech TRUE

D. It is orally not orally bioavailable because of it is not degraded by cytidine deaminase

which is present in the gastrointestinal epithelium and liver. FALSE
 6. Which purine analog must have dose reduction when co-administered with
Allopurinol?

A. 6-mercaptopurine
B. 6-thioguanine
C. Both
D. Neither

•Allopurinol inhibits the metabolic inactivation of 6-MP, but not of 6-TG.

o Therefore, it is recommended that dosages of orally administered 6-
MP be reduced by 75% in patients receiving allopurinol.
7. The major toxicities of HU are leukopenia and __________________.
The leukocyte nadir occurs __________ days after a single dose of drug,

A. Anemia; 3 to 5
B. Thrombocytopenia; 5 to 7
C. Anemia; 5 to 7
D. Thrombocytopenia; 3 to 5
 8. The only anthracycline amenable to oral administration
A. Daunorubicin
B. Doxorubicin
C. Idarubicin
D. Epirubicin

•Idarubicin, the only anthracycline amenable to oral administration, has a

bioavailability of 20% for the parent drug and 40% for the parent drug plus idarubicinol, the
primary active metabolite.
o Idarubicinol has a very prolonged biologic half-life, ranging from 50 to 60
hours, and is likely responsible for the antitumor activity of this drug.
o In contrast to the metabolites of doxorubicin and daunorubicin, idarubicinol is
eliminated primarily by renal excretion.
o No dose adjustment for hepatic dysfunction is indicated. 
9. TRUE regarding Dexrazoxane EXCEPT:

A. As cardiotoxicity of anthracyclines results from the generation of free radicals by an

anthracycline–iron complex, dexrazoxane, an iron chelator, decreases free radical formation
in vitro and decreases the risk of cardiotoxicity in children receiving treatment for ALL, and
in adults with metastatic breast cancer as well

B. Dexrazoxane causes does not cause apparent diminution of antitumor activity of

anthracyclines.

C. In adult patients, dexrazoxane should be added only in patients who have received a total
dose of at least 300 mg/m2 doxorubicin.

D. Dexrazoxane injected subcutaneously lessens tissue damage after extravasation to prevent

tissue necrosis.
10. What is the dose-limiting
extramedullary toxicity of high-dose
Cyclophosphamide?

A. Cardiac
B. Renal
C. GI
D. CNS
11. TRUE OR FALSE | BLEOMYCIN and L-ASPARAGINASE

A. The clinical risk of pulmonary toxicity with Bleomycin is related to the cumulative dose of BIP(Bleomycin
Induced Pneumonitis) administered, with the risk increasing to 10% in patients given more than 500 450 mg
over the patient’s lifetime. FALSE

B. In patients who have received bleomycin, O2 supplementation during subsequent surgery must be avoided,
as it promotes the oxidative injury to pulmonary tissue. TRUE

C. Hyperdiploid ALL cells are particularly sensitive to l-asparaginase, whereas lymphoid leukemia cells
containing the BCR-ABL translocation are more resistant. TRUE

D. L-asparginase purified from Erwinia chrysanthemi, Pegaspargase and calaspargase have long plasma half-
lives, are less likely to cause hypersensitivity, and are used for first-time therapy and for patients
hypersensitive to the unmodified enzyme. FALSE

E. Another major toxic effects of l-asparaginase are a consequence of the ability of this drug to inhibit protein
synthesis in normal tissues, resulting in hypoalbuminemia, a decrease in clotting factors, a decrease in
serum lipoproteins, and a marked increase in plasma triglycerides, which predisposes to pancreatitis. TRUE
12. Differentiation syndrome caused
• Approximately 15% of patients with APL,
by ATRA and ATO can effectively beparticularly those with an initial leukemic cell
count greater than 5000/μL, develop a
reversed with: differentiation syndrome of
hyperleukocytosis, fever, altered mental
status, pleural and pericardial effusions,
A. Glucocorticoids and respiratory failure.
B. HU • Increased leukocyte adherence to small vessels
in the lung results from the increased
C. Both expression of integrins on the leukemic cell
D. Neither surface and from leukocyte secretion of
cytokines in response to ATRA.
• Glucocorticoids and HU are effective in
reversing this syndrome.
• ATRA should be continued unless severe
symptoms supervene.
13. Which among the histone deacetylase inhibitors is regarded as the most
potent pan-HDAC inhibitor, and is approved in combination with bortezomib and
dexamethasone, for relapsed or refractory multiple myeloma.
A. Vorinostat

B. Romidepsin

C. Panobinostat

D. Belinostat
14. Only TKI agent with activity against the gatekeeper mutation
T315I

A. Imatinib
B. Nilotinb
C. Bosutinib
D. Dasatib
E. Ponatinib
15. The following are FLT3 Tyrosine Kinase Inhibitors EXCEPT

A. Midostaurin
B. Ivosidenib
C. Gilteritinib
D. Sorafenib
16. Venetoclax works by tipping of the
balance toward apoptosis by preventing key
BH3 proteins from binding to antiapoptotic
proteins. Antiapoptotic proteins include the
following EXCEPT

A. MCL1
B. BCL2
C. BAK
D. NONE OF THE ABOVE
17. Dose adjustment for Lenalidomide for patients with SEVERE renal
impairment (CrCl <30 ml/min)

A. 10 mg/day - moderate (CrCl of 30–50 mL/min)

B. 10 mg every other day
C. 5 mg once daily- on dialysis
D. No dose adjustment
18. MATCHING TYPE | MONOCLONAL ANTIBODIES (0.1
EACH)
A. CD19
i. Rituximab B B. CD20
ii. Ofatumumab B C. CD22
iii. Obinutuzumab B D. CD30
iv. Alemtuzumab G E. CD33
v. Brentuximab D F. CD38
vi. Gemtuzumab Ozogamicin E G. CD52
vii. Inotuzumab Ozogamicin C H. Signaling lymphocytic
viii. Blinatumomab A activation molwcule
ix. Daratumumab F family 7 (SLAMF7)
x. Isatruximab H
19. MATCHING TYPE | ADVERSE EFFECTS (0.1 EACH)

i. Fludarabine A A. Hemolytic anemia with warm

ii. Vincristine B or cold antibodies
iii. Doxorubicin D B. Neurotoxicity
iv. Etoposide and Tenoposide C C. Leukopenia
v. Busulfan, Bleomycin E D. Cardiotoxicity
vi. Bortezomib J E. Pulmonary Fibrosis
vii. Cyclophosphamide and Ifosfamide F F. Chronic Bladder Toxicity
viii. L-asparaginase G G. Hypersensitivity/Anaphylaxis
ix. ATRA H H. Pseudotumor cerebri
x. Fedratinib I I. Fatal Wernicke
encephalopathy
J. Sensory peripheral neuropathy
20. MATCHING TYPE | Antineoplastic Drugs: Hematologic Malignancy (0.1
EACH)
A. Gastrointestinal stromal tumor
i. Fludarabine H and systemic mastocytosis
ii. Cladribine F B. APL
iii. Nelarabine G C. Glioblastoma
iv. Pentostatin F D. Hodgkin lymphoma
v. Hydroxyurea E E. Sickle Cell Disease Crisis
vi. Vinblastine D F. Hairy Cell Leukemia
vii. Temozolomide C G. T cell lymphoblastic lymphoma
viii. ATRA B and Acute T cell leukemias
ix. Arsenic Trioxide B H. CLL
x. Imatinib A
BONUS: MAX OF 1 POINT
1. Dose of intrathecal methotrexate: 12 mg cytarabine: 50-70 mg

2. Vinblastine and vincristine are derived from the vinca rosea or

periwinkle plant

3. Formula for area under the curve AUC= Dose (mg/m2)/(glomerular

filtration rate + 25
MORPHOLOGY
1. IDA 2. TTP