1.
A 69-year-old man with a large-cell lymphoreticular lymphoma was started on a chemotherapeutic regimen of cyclophosphamide, doxorubicin, vincristine, prednisone and bleomycin 1 year ago. Three weeks after his sixth course he developed dyspnea, a nonproductive cough and fever. Chest x-ray showed diffuse bilateral infiltrates and a lung biopsy revealed inflammation and fibrosis with no evidence of lymphoma. Bacterial, fungal and viral cultures were negative. Which of the drugs administered to the patient could have caused this pulmonary disorder?
Correct Answer
E. Bleomycin
Explanation
Answer: E
The patient is at risk for several processes that could produce his symptoms, but the exam results ruled
out bacterial infections and the progression of lymphoma. Therefore pulmonary toxicity resulting from
one or more of the drugs he received is a plausible hypothesis.
Among the anticancer drugs bleomycin most commonly caused pulmonary toxicity, mainly interstitial
pneumonitis followed by pulmonary fibrosis. The mortality associated with bleomycin pulmonary toxicity
is about 50%.
Other anticancer drugs that can cause pulmonary toxicity include cyclophosphamide, methotrexate,
carmustine and vinblastine, but the risk is much lower than that of bleomycin.
2.
A 6-year-old child presented with hematuria and complained of pain when urinating. The child, recently diagnosed with neuroblastoma, had begun a chemotherapy program five days previously. Which of the following drugs most likely caused the patient’s symptoms?
Correct Answer
D. CyclopHospHamide
Explanation
Answer: D
Gross hematuria can be either painless or painful. While the former can have many causes, painful
hematuria is usually due either to inflammatory disease of the urogenital tract (cystitis, prostatitis), or to
renal infarction or to nephrolithiasis. Renal infarction and renal calculi are quite unusual in a very young
child. Cyclophosphamide can cause hemorrhagic cystitis with bladder mucosa edema, ulcerations, and
minor to severe hemorrhage. This toxicity is believed to be due to metabolites of cyclophosphamide
including chlorethylaziridine and acrolein which are formed by hepatic microsomes and excreted in the
urine. They concentrate in the bladder and cause mucosa damage. The incidence of hemorrhagic cystitis
from cyclophosphamide administered at conventional doses is unknown but in patients receiving high
dose regimens is about 10%.
A, B) Adverse effects of prednisone and vincristine do not include gross hematuria
C, E) Cisplatin and (very rarely) doxorubicin can cause nephrotoxicity but hemorrhagic cystitis has not
been reported.
3.
Which of the following anticancer drugs exhibit dose-limiting toxicity to bone marrow?
(Check all that apply)
Correct Answer(s)
A. CyclopHospHamide
E. Doxorubicin
F. Cytarabine
Explanation
Answer: AEF
Most anticancer drugs exhibit a dose limiting toxicity to bone marrow. These dugs include alkylating
agents, antimetabolites, anthracyclines, taxanes and topoisomerase inhibitors.
B) Unlike vinblastine, vincristine causes very little myelosuppression. The reason of this difference is still
uncertain.
C, D, G, H, I ) These drugs cause very little or negligible myelosuppression.
4.
A 12-year-old girl suffering fro acute lymphoblastic leukemia received an anticancer therapy, which included high dose methotrexate. Leucovorin was also given along with methotrexate. Which of the following concepts specifically underlies this therapeutic strategy?
Correct Answer
E. Rescue therapy
Explanation
Answer: E
Rescue therapy is a strategy aimed at alleviating some adverse effects of anticancer chemotherapy by
the use of drugs that can “rescue” the normal cells exposed to the anticancer drug. Leucovorin (formyl
tetrahydrofolate, also called folinic acid ) is accumulated more readily by normal than by neoplastic cells.
The administration of this drug results in rescue of the normal cells, since the drug bypasses the step, in
the purine synthesis, which is blocked by methotrexate (i.e. dihydrofolate to tetrahydrofolate).
A) The log kill concept refers to the fact that a given dose of an anticancer drug kills a constant
proportion (not a constant number) of the tumor cell population.
B) Recruitment refers to a strategy that involves initial use of kill CCNS drugs to achieve a significant cell
kill. This kill “enrolls” previously resting cells in the G0 phase of the cell cycle. At this stage CCS drugs
are given. Since these drugs are active against dividing cells , maximal cell kill may be achieved.
C) This anticancer strategy involves cycles of treatment with very high doses of an anticancer drug.
Between cycles normal cells can recover from the cytotoxic effects of the drug.
D) Combination therapy is the rule in anticancer treatment and is usually done with drugs having different
mechanism of action and (when possible) different toxic effects
5.
A 10-year-old girl, recently diagnosed with a lymphoblastic T-cell lymphoma, received her first combination chemotherapeutic regimen which included cyclophosphamide, vincristine, doxorubicin and prednisone. Which of the following adverse effects was the patient most likely to suffer from, during the first day of treatment?
Correct Answer
E. Nausea and vomiting
Explanation
Answer: E
Nausea and vomiting are among the most common complications of chemotherapy administration. It has
been shown that on the first day of chemotherapy nausea is present in 50% and vomiting in about 25%
of patients. The most important factor influencing the frequency of nausea and vomiting is the
emetogenic potential of the drug . Among the drugs administered to this patient, cyclophosphamide and
doxorubicin are highly emetogenic, whereas the emetogenic potential of vincristine is low.
Corticosteroids on the other hand are effective antiemetics mainly in chemotherapy-induced nausea and
vomiting, but the basis for this effect is unknown.
A, B, C, D) All these listed adverse effects can occur (neuropathy with vincristine, hemorrhagic cystitis
and, rarely, pulmonary fibrosis with cyclophosphamide, congestive heart failure with doxorubicin) but
they are much less frequent than nausea and vomiting and are not acute adverse effects.
6.
A 47-year-old man with a non-Hodgkin’s lymphoma is being treated with CHOP
(cyclophosphamide, doxorubicin, vincristine and prednisone) and rituximab. He is in the clinic to receive his four cycle of CHOP. Physical examination reveals tachycardia, shortness of breath, neck vein distension, pulmonary rales and ankle edema. Which of the following drugs has most likely caused this findings?
Correct Answer
B. Doxorubicin
Explanation
Answer: B
The CHOP regimen has been considered the best treatment in terms of initial therapy for patient with
diffuse non-Hodgkin’s lymphoma. Recently it has been shown that the combination of CHOP with
rituximab results in improved response rates, disease-free survivals and overall survivals compared with
CHOP chemotherapy alone.
The signs and symptoms of the patient strongly suggest the diagnosis of cardiac failure. Anthracyclines
(doxorubicin, daunorubicin, idarubicin, etc.) are the anticancer drugs that have the highest risk of cardiac
toxicity. They can cause a dose dependent dilated cardiomyopathy associated with a potentially fatal
cardiac failure. This toxicity appears to result from increased production of free radicals within the
myocardium.
A, C, D, E) These drugs have a low (cyclophosphamide ) or negligible risk of cardiac toxicity
Other anticancer drugs that can cause some cardiac toxicity include fluorouracil, paclitaxel and
trastuzumab.
7.
A 12-year-old boy presents with fatigue, malaise and nosebleed. He has a one week history of an upper respiratory tract infection and otitis media. A blood examination reveals a normochromic, normocytic anemia and a differential white blood cell count shows 11% lymphoblasts. A bone marrow biopsy is performed which reveals 95% lymphoblasts. Which of the following pairs of drugs are most likely included in the therapeutic management of this boy?
Correct Answer
C. Vincristine and prednisone
Explanation
Answer: C
The symptoms and signs of the patient strongly suggest the diagnosis of leukemia and the bone marrow
biopsy confirms the diagnosis of acute lymphoblastic leukemia. A combination of vincristine and
prednisone (sometimes plus asparaginase and daunorubicin) is the current therapy of choice to induce
remission, since none of these agents is myelosuppressive to normal bone marrow elements. Over 90%
of children enter complete remission with this treatment.
A) This combination is currently used for lung and testicular cancers.
B) This combination is currently used for prostate cancer.
D) this drugs are used to treat breast cancer.
E) This combination is currently used for head and neck cancers.
8.
A 66-year-old woman with inoperable lung cancer is being treated with a combination
chemotherapy regimen. Laboratory exams reveal the following plasma levels: reatinine 7.5 mg/dL (normal: 0.6-1.5), BUN 45 mg/dL (normal 7-30), Mg++ 0.2 mmol/L (normal 0.6-1.0). Which of the following drugs most likely caused these laboratory abnormalities?
Correct Answer
D. Cisplatin
Explanation
Answer: D
The lab results of this patient strongly suggest the diagnosis of renal failure. Cisplatin is the anticancer
drugs with the highest risk of nephrotoxicity, and hypomagnesemia is the most common electrolyte
abnormality caused by cisplatin. However the routine use of hydration and diuresis has been largely
reduced cisplatin-induced nephrotoxicity.
A, B, C, E) All these drugs rarely cause nephrotoxicity.
9.
Which of the following drugs can be used most effectively against chemotherapy-induced nausea and vomiting? (Check all that apply)
Correct Answer(s)
A. Ondansetron
D. Aprepitant
F. Dexamethasone
Explanation
Answer: ADF
The first choice drugs used in chemotherapy induced emesis are 5-HT3 antagonists (ondansetron) NK1
antagonists (aprepitant) and glucocorticoids (dexamethasone). Other drugs like D2/5-HT3 antagonists
(metoclopramide), D2 antagonists (i.e. phenothiazines, butyrophenones) and cannabinoids (dronabinol)
are used only in patient intolerant or refractory to first line drugs.
B, C; E) Antihistamines (diphenhydramine, meclizine) and antimuscarinic drugs (scopolamine) have
negligible antiemetic activity against chemotherapy-induced nausea and vomiting.
10.
Which of the following statements correctly pair the anticancer drug with the enzyme it is able to inhibit, either directly or through its active metabolite?
(Check all that apply)
Correct Answer(s)
C. Mercaptopurine - pHospHoribosyl pyropHospHate synthetase
E. Fluorouracil - thymidylate synthetase
F. Topotecan - topoisomerase I
G. Pentostatin - adenosine deaminase
Explanation
Answer: CEFG
Mercaptopurine is biotransformed into a false purine nucleotide which inhibits the enzyme
phosphoribosyl pyrophosphate synthetase, a major control point in purine synthesis
Fluorouracil is activated to a false nucleotide which inhibit thymidylate synthetase, the enzyme
responsible for converting deoxyuridine monophosphate to deoxythimidine monophosphate.
Topotecan inhibits topoisomerase I, an enzyme that breaks and reseals single-stranded DNA.
Pentostatin inhibits adenosine deaminase so leading to accumulation of intracellular adenosine, which
blocks DNA synthesis
A) Hydroxyurea inhibits ribonucleotide reductase.
B) Doxorubicin inhibits topoisomerase II
D) Cytarabine blocks DNA elongation.
11.
Which of the following is a mechanism for multidrug resistance in cancer chemotherapy?
Correct Answer
C. Increased synthesis of the cell surface glycoprotein P-170
Explanation
Answer: C
Anticancer drugs resistance can develop to a single drug or to a variety of drugs of different structures,
after the exposure to a single agent.
Single drug resistance can be due to:
1) Decreased sensitivity of a target enzyme
2) Decreased target receptor affinity to the drug
3) Increased inactivation of drugs
4) Decreased activation of prodrugs
Multidrug resistance can be due to:
1) Increased efflux of the drug from the cells, due to increased expression of a normal gene for a cell
surface glycoprotein (P-170) which uses the energy of ATP to expel a variety of foreign molecules (this
is the most common mechanism of multidrug resistance)
2) Increased DNA repair, due to increased activity of topoisomerase enzymes.
A) DNA repair is increased, not decreased, in case of multidrug resistance.
B) This can explain the resistance to methotrexate (the drug that inhibits dihydrofolate reductase) but
cannot account for multidrug resistance.
D, E) These events are decreased, not increased, in case of drug resistance.
12.
Which of the following statements regarding antimetabolite anticancer drugs is correct? (Check all that apply)
Correct Answer(s)
A. They are CCS anticancer drugs
E. Their mechanism of action involve the inhibition of enzymes needed for nucleic acid synthesis
Explanation
Answer: AE
Antimetabolite anticancer drugs act in the S phase of the cell cycle. This is a consequence of their
mechanism of action. Since they inhibit enzymes needed for nucleic acid synthesis they act when
nucleic acid synthesis takes place, that is in the S phase.
B) These toxicities occur only with high doses of fluorouracil (cardiotoxicity) or methotrexate
(nephrotoxicity).
C) folate analogs (methotrexate) and purine analogs (mercaptopurine and thioguanine) can be given
PO, but pyrimidine analogs (fluorouracil, cytarabine and fludarabine) are not active by oral route.
D) Resistance to these drugs always occurs.
13.
Which of the following statements regarding vincristine are correct?
(Check all that apply)
Correct Answer(s)
A. It is a cell cycle specific agent
B. Neurotoxicity is a significant adverse effect
E. It is a component of the combination therapy for leukemias and lympHomas
Explanation
Answer: ABE
Vincristine is a plant alkaloid that acts in the M phase of the cell cycle. It can cause a peripheral
neuropathy in more than 50% of patients treated chronically. The drug is frequently used in the
combination therapy of leukemias and lymphomas.
C) Hemorrhagic cystitis is an adverse effect of cyclophosphamide.
D) This is a mechanism of action of alkylating agents, not of Vinca alkaloids.
14.
Which of the following statements regarding etoposide are correct?
(Check all that apply)
Correct Answer(s)
A. It is a cell cycle specific agent.
C. Toxicity to the hematopoietic and lympHoid system can be pronounced
E. It is mainly used for treatment of testicular and lung cancers
Explanation
Answer: ACE
Etoposide is a topoisomerase inhibitor that acts mainly in the S and G2 phases of the cell cycle. It
causes a dose-limiting myelosuppression and is mainly used for testicular cancer and small cell lung
cancer.
B) Resistance to this drug always occurs.
D) This is the mechanism of action of fluorouracil. Etoposide blocks topoisomerase II.
15.
The diagram below depicts a simplified pathway for the synthesis of DNA and RNA.
Which of the steps shown in the pathway are specifically inhibited by methotrexate?
(Check all that apply)
Correct Answer(s)
A. 1
B. 2
Explanation
Answer: AB
Methotrexate inhibits dihydrofolate reductase, the enzyme that catalyzes the reduction of folate to
dihydrofolate and the reduction of dihydrofolate to tetrahydrofolate. Methotrexate itself can inhibit the
enzyme but, in vivo, it is activated intracellularly to polyglutamated methotrexate, which has a higher
inhibitory activity on the enzyme.
C, D, E) These steps are not inhibited by methotrexate.
16.
Which of the following statements regarding asparaginase are correct?
(Check all that apply)
Correct Answer(s)
B. It inhibits protein synthesis in lympHoblastic leukemic cells
C. It acts on the G1 pHase of the cell cycle
D. It metabolizes circulating asparagine
Explanation
Answer: BCD
Asparaginase is an enzyme that catalyzes the hydrolysis of circulating asparagine to aspartic acid and
ammonia. Certain neoplastic cells, including acute lymphoblastic leukemic cells, require exogenous
asparagine for protein synthesis and therefore the lack of this amino acid inhibits cell proliferation and
activates apoptosis. The drug is CCS and acts mainly in the G1 phase of the cell cycle. Most normal
cells can synthesize asparagine and thus are less exposed to the action of asparaginase.
A) Asparaginase catalyzes the breakdown, not the synthesis of asparagine
E) Asparaginase causes very little myelosuppression. The main adverse effect of the drug is a
hypersensitivity reaction manifested by fever , nausea and vomiting, skin rash and urticaria.
17.
Which of the following statements regarding anticancer drugs are correct?
(Check all that apply)
Correct Answer(s)
A. Toxicity of anticancer drugs is often serious enough to require the suspension of the treatment
D. Acquired drug resistance develops in many drug-sensitive cancers
F. Anticancer drugs tend to send the cells into the programmed cell death (apoptosis)
Explanation
Answer: ADF
Toxicity of anticancer drugs is the first reason of failure of anticancer chemotherapy. These drugs are
toxic not only to cancer cells but also to various tissues and organs. Therefore toxicity is dose-limiting,
that is a factor that restricts the use of potentially curative doses.
Resistance to anticancer drugs is the second reason of failure of anticancer chemotherapy. Resistance
can occur de novo or can develop during cell division as a result of mutation. Cancer cells are gene
labile and therefore have an intrinsic ability to develop resistance to drugs by changing the cell genetic
apparatus with amplification or increased expression of one or more specific genes, which in turn can
cause a single or multidrug resistance.
Apoptosis is the genetically programmed cell death. In contrast, necrosis is a cell death due to external
causes (i.e. lack of oxygen or nutrients). When the DNA of a proliferating cell is sufficiently damaged,
the cell arrests in G2 and undergoes apoptosis. It has been shown that most anticancer drugs can
facilitate apoptosis, which is likely a consequence of the drug-induced damage of DNA of proliferating
cells.
B) Advanced (i.e disseminated) cancers rarely can be cured completely even if chemotherapeutic
treatment can prolong survival in several cases.
C) Combination therapy with two or more anticancer drugs is the rule for most malignancies since it
provides broader coverage against resistant cell lines and prevents the development of resistant clones
without increasing toxicity.
E) (see explanation of toxicity above)
18.
Which of the following statements correctly pair the anticancer drugs with their likely
mechanism of action? (Check all that apply)
Correct Answer(s)
C. Dactinomycin - binds to double-stranded DNA
F. Vincristine - inhibits tubulin polymerization
G. Etoposide - inhibits topoisomerase II
Explanation
Answer: CFG
Most cytotoxic antibiotics (including dactinomycin and anthracyclines) bind strongly to DNA by inserting
themselves between paired bases of double-stranded DNA, thereby causing deformation and uncoiling
of DNA. Therefore the synthesis of both DNA an RNA are blocked.
Vinca alkaloids bind to tubulin and inhibit tubulin polymerization. In this way they prevent microtubule
assembly, so blocking cell mitosis at metaphase.
Etoposide inhibits topoisomerase II, the enzyme that breaks and reseals double-stranded DNA.
A, B, D, E) All these mechanism of action are wrongly paired.
19.
Which of the following statements correctly pair the class of anticancer agents with the
specificity of their action on the cell cycle? (Check all that apply)
Correct Answer(s)
A. Alkylating agents - cell cycle nonspecific
B. Antimetabolites - cell cycle specific
D. Anthracycline antibiotics - cell cycle nonspecific
Explanation
Answer: ABD
An anticancer drug is called cell cycle non-specific (CCNS) when it acts on tumor stem cells both when
they are in the resting phase and when they are traversing the cell cycle. It is instead called
Cell cycle specific (CCS) when it acts on tumor stem cells only when they are traversing the cell cycle.
CCNS drugs include alkylating agents and cytotoxic antibiotics (except bleomycin).
CCS drugs include antimetabolites, antimitotic drugs, topoisomerase inhibitors, bleomycin, hydroxyurea
and asparaginase.
C, E) All these drugs are CCS
20.
Which of the following toxicities are common to most anticancer drugs?
(Check all that apply)
Correct Answer(s)
A. Bone marrow suppression
E. Nausea and vomiting
F. Alopecia
Explanation
Answer: AEF
Since anticancer drugs are cytotoxic, certain adverse effects are common to most agents. These
toxicities occur as a result of inhibition of host cell division, mainly in those tissues with rapid renewal of
cell population. These include bone marrow, lymphoid tissue, gonads, lining epithelium of the
gastrointestinal tract, oral mucosa and hair follicles.
Bone marrow depression leads to leukopenia and thrombocytopenia and this depression is doselimiting.
However the extent of this depression during the first course of treatment can help determine
the dosage and concurrent chemotherapy for subsequent courses.
Because hair bulb cells replicate every 12 to 24 hours, they are quite susceptible to various
chemotherapeutic agents. Hair loss usually begins after few days of chemotherapy and may be
prominent after one month. Alopecia is reversible and usually hair regeneration occurs 1-2 months after
discontinuation of the treatment.
About 70-80% of patients will experience nausea and vomiting during chemotherapy. In more than 50%
of these patients nausea starts the first day of chemotherapy. It is though that the pathophysiology of
the syndrome involves both central and peripheral mechanisms mediated by various neurotransmitters.
The two most important neurotransmitters seem serotonin and substance P. It has been postulated that
chemotherapy-induced local irritation and damage of the GI mucosa causes a release of serotonin from
enterochromaffin cells of the GI tract. Serotonin in turn will activate 5-HT receptors located in the gut
(afferent fibers of the vagus nerve) as well as and .in the CTZ
Substance P (also released from the GI mucosa) is thought to activate a neurokinin-1 receptor located in
the gut as well as in the nucleus of tractus solitarius. Aprepitant, a neurokinin-1 receptor antagonist, has
been recently approved for the treatment of chemotherapy induced nausea and vomiting.
B) This adverse effect is mainly caused by bleomycin
C) This adverse effect is mainly caused by vincristine
D) This adverse effect is mainly caused by cyclophosphamide
G) This adverse effect is mainly caused by anthracyclines
H) This adverse effect is mainly caused by cisplatin