Pharm Antineoplastic Drugs Part 2

Answer: C
Cyclophosphamide can cause a hemorrhagic cystitis which seems to be due mainly to acrolein, an active
metabolite. Prevention consists of providing adequate IV hydration and administration of MESNA (2-
mercaptoethane sulfonate) that is thought to work by inactivating acrolein.
A, B, D, E) All these drugs cannot prevent cyclophosphamide-induced hemorrhagic cystitis.

Answer: C
The results of lymph node biopsy confirm the diagnosis of Hodgkin’s disease. Reed-Steinberg cells are
giant connective tissue cells with one or two large nuclei. These cells are specific to are Hodgkin’s
lymphoma ad are therefore diagnostic markers of the disease. Hodgkin’s disease is classified in 4 stages
according to its extent. In the present case the disease is stage IV because of extranodal (mediastinal)
involvement.
Two 4 drug combination regimens have demonstrated equivalent long-term survival rates in advanced
Hodgkin’s disease. These regimens are the MOPP regimen (mechlorethamine, vincristine procarbazine
and prednisone) and the ABVD regimen. However the MOPP regimen is associated with a higher risk of
toxicity and therefore the ABVD regimen is currently the preferred one.
A, B, D, E) These malignancies do not show Reed-Sternberg cells and are not treated with the ABVD
regimen.

Answer: A
The patient paresthesias and loss of reflexes are signs of vincristine peripheral neuropathy, which often
appears within the first few weeks of therapy. Areflexia is common in patients treated with high
cumulative doses. Vinca alkaloids have certain toxicities in common (i.e. nausea and vomiting, diarrhea,
alopecia) but other adverse effects differ. Vincristine causes a dose-limiting neurotoxicity but is a mild
myelosuppressant, whereas vinblastine causes negligible neurotoxicity but gives rise to a severe, doselimiting
myelosuppression.
B, C, D, E) The risk of peripheral neuropathy with these drugs is negligible.

Answer: D
Dactinomycin is a cytotoxic antibiotic. Its main mechanism of anticancer action involves binding to
double-helical DNA so preventing DNA transcription and RNA synthesis. Dactinomycin is used mainly in
Wilms’ tumor, a kidney tumor that is the most common intra-abdominal tumor of childhood and accounts
of about 6% of all childhood malignancies.
A) This is the mechanism of action of alkylating drugs
B) This is the mechanism of action of methotrexate
C) This is the mechanism of action of pyrimidine analogs
E) The formation, not the inhibition, of free radical is one of the postulated mechanisms of action of
some anticancer drugs including doxorubicin and bleomycin.

Answer: A
Methotrexate is a folic acid antagonist that inhibits dihydrofolate reductase, the enzyme responsible for
the reduction of dihydrofolate to tetrahydrofolate. The drug is biotransformed intracellularly to
polyglutamated derivatives that are selectively retained within cancer cells and have a higher inhibitory
effect on the enzyme. The inhibition of dihydrofolate reductase leads to a decreased synthesis of
tetrahydrofolate, which is a one carbon unit carrier. These one carbon units are used in the synthesis of
purine and pyrimidine, which in turn are essential for the synthesis of DNA and RNA.
B) This is the mechanism of action of cytarabine.
C) This is the mechanism of action of hydroxyurea .
D) This is the mechanism of action of etoposide.
E) This is the mechanism of action of Vinca alkaloids .

Answer: B
Carmustine belongs to nitrosoureas. These alkylating agents have a high lipophilicity that facilitates their
entry into the brain. In fact their concentration in the CSF are 15-30% of the concurrent plasma values.
Because of this, nitrosoureas are mainly used in the treatment of brain tumors.
A) Nitrosoureas are CC NS agents that actually may kill most neoplastic and non neoplastic cells.
C) Carmustine actually can cause encephalopathy, when given in high doses.
D) The amine pump is specific for monoamines. Nitrosoureas are not monoamines.
E) Nitrosoureas undergo a spontaneous degradation in most body fluids, with formation of active
metabolites which alkylate DNA

Answer: A
Doxorubicin is an anthracycline antibiotic. These anticancer drugs likely act by multiple mechanisms
including the following :
1) They can intercalate between adjacent base pairs of DNA so causing blockade of DNA replication.
2) They block topoisomerase II, the enzyme which catalyzes DNA repair.(it breaks and then reseals DNA
strands).
3) They generate free radicals which can oxidize DNA bases.
The end result of these multiple mechanisms is cell apoptosis.
B) This would be the mechanism of action of taxanes
C) This would be the mechanism of action of Vinca alkaloids
D) This would be the mechanism of action of alkylating drugs
E) This would be the mechanism of action of methotrexate.

Answer: B
Bleomycin is the only cytotoxic antibiotic that is CCS. It has been shown that the drug causes
accumulation of cells in the G2 phase of the cell cycle
A, D) These drugs are CC NS
C) Vinblastine is CCS but act in the M phase of the cell cycle.

Answer: E
The blood exam and the bone marrow biopsy are consistent with the diagnosis of acute lymphoblastic
leukemia. Before CNS preventive therapy was routine, the CNS was the most common site of leukemic
relapse in children with acute lymphoblastic leukemia. Today preventive therapy is performed with
intracranial irradiation and intrathecal administration of anticancer drugs. Methotrexate (with or without
cytarabine and corticosteroids) is the most common drug administered intrathecally to prevent relapse.
A, B, C. D) these drugs are not currently used to treat acute lymphoblastic leukemia and are not
administered intrathecally.

Answer: C
The signs of the patient strongly suggest a prostate cancer and the exam results confirm the diagnosis
of prostatic carcinoma. The PSA is the most used lab test for early detection of prostate cancer, and
spine metastases with prevalent necrotic lesions are the most common metastases of prostatic
carcinoma. The mainstay of treatment for metastasized prostate cancer is hormonal therapy. Since the
cancer is testosterone dependent, hormonal manipulation is centered to reduce testosterone levels.
Leuprolide is a synthetic GnRH analog. When administered daily (or as a depot preparation) to maintain
stable blood levels, it inhibits the release of FSH and LH, likely due to down-regulation of pituitary
receptors. This inhibition strongly reduces testicular androgen synthesis. Flutamide is a androgen
receptor antagonist. Combined treatment with these two drugs reduces symptoms in 70-80% of patients,
causes an appreciable regression of established metastases and prolongs survival. On the contrary
cytotoxic chemotherapy failed to prolong survival in patient with advanced prostate cancer.
A) This is the most common therapy for advanced ovarian cancer.
B) This is the most common therapy for acute lymphoblastic leukemia.
D) These drugs are used in hormone receptor positive breast cancer.
E) These drugs are used in Wilms tumor.

Answer: A
Ototoxicity, characterized by a progressive hearing loss, commonly occurs with cisplatin and appears to
be more pronounced in children. The reversibility of this ototoxicity is questionable and it seems
substantial only with early cessation of cisplatin. Ototoxicity does not appear to be associated with other
platinum analogs (carboplatin, oxaliplatin).
B, C, D, E) The risk of ototoxicity with these drugs is negligible.

Answer: A
The WBC count and the presence of the Philadelphia chromosome confirm the diagnosis of chronic
myelogenous leukemia. The disease ( which is associated with the Philadelphia chromosome in over
90% of cases) is characterized by increased granulocytes in peripheral blood and often increased
platelets in early stages, as in the present case. The goal of chemotherapy in chronic myelogenous
leukemia is to reduce leukocytosis and its associated symptoms. Hydroxyurea is still the most common
agent used for leucocyte reduction. However interferon-alpha and the monoclonal antibody imatinib
seem to give better results in term of remission and 5 year survival.
B, C; D, E) All these agents are antibacterial, not anticancer, drugs.

Answer: C
Maintenance therapy of acute lymphoblastic leukemia is usually performed for 2.5-3 years after
remission since early trials have shown that, without maintenance, most children will relapse within 1 or 2
months. Impressive improvements in disease-free survival are achieved with various maintenance
regimens. Methotrexate and mercaptopurine are the drugs most often included in these regimens.
Mercaptopurine is effective and well tolerated orally when administered daily.
A, B, D, E) All these drugs are NCCS.

Answer: E
The symptoms of the patient and the bronchial biopsy are consistent with the diagnosis of a small cell
lung cancer. Although the risk of developing any type of lung cancer increases with cigarette smoking,
the relative risk of small cell lung cancer is among the highest. The cell of these cancers, also called ‘oat
cell’ carcinomas, contain a scanty amount of cytoplasm and rarely have nucleoli. These malignancies,
which are of neuroendocrine origin, may cause a variety of paraneoplastic syndromes due to the
synthesis and secretion of hormones such as ACTH and serotonin. Small cell lung cancers carry a poor
prognosis since they metastasize early and are already spread at the time of diagnosis. Etoposide, given
together with a platinum compound, has been shown to improve significantly survival and is today a drug
of choice in this disease.
A, B, C) These drugs are antimicrobial agents and are therefore of no value in lung cancer.
D) Asparaginase is an anticancer drug used in childhood lymphoblastic leukemia.

Answer: E
Because of significant relapse rate in patients with extensive colon cancer, adjuvant therapy is usually
performed in those patients who underwent potential curative surgery, since it has been shown to
improve disease-free survival. Fluorouracil plus leucovorin given for 6 months is the most commonly
used regimen. Leucovorin is given because it has been shown that, by increasing the intracellular
concentration of a reduced folate (i.e. leucovorin), the formation of a stable complex between the
fluorouracil metabolite, the reduced folate and the thymidylate synthetase will be favored, so increasing
the cytotoxicity of fluorouracil.
A, B, C, D) These drugs are all CCS and are mainly used in tumors with a high grow fraction. They are
not currently used in the post surgical therapy of colon cancer, a tumor with low growth fraction

Answer: B
(Golan, pp 499, Koda-Kimble, pp 88-15)
The therapeutic strategy adopted in this case is based on the ‘log kill’ rule. This rule states that a given
dose of an anticancer drug will kill a constant proportion (not a constant number) of the tumor cell
population. In other words, killing by anticancer drugs is a first order process, and the curve representing
the number of killed cells with increasing dose of an anticancer drug is an exponential curve. This curve
can be transformed into a straight line by plotting the logarithm of the number of killed cells against the
dose. Remembering that the logarithm is the exponent required to produce a given number, it follows
that 1 is the log of 10 , 2 is the log of 10 (that is 100), 1 2 3 is the log of 103 (that is 1000) and so on.
Therefore if a population of 103 tumor cells is reduced to 102 tumor cells it can be said that it is reduced
by 1 log. This means that 900 cells are killed by the drug, resulting in a 90% decrease of cell number.
Accordingly a 2 log decrease means that 99% of the cells are killed, a 3 log decrease that 99.9% of the
cells are killed, and so on. Usually a 2 log decrease is the strategy most often used since a higher
decrease would produce unacceptable toxicity on healthy dividing cells.

Answer: D
Ovarian cancer is the fifth most common cause of cancer and cancer death in women. Since the cancer
is relatively asymptomatic usually it has extended beyond the pelvis at the time of diagnosis. Therefore
chemotherapy is indicated after surgery. Cisplatin or carboplatin plus paclitaxel is the first-line regimen
most commonly used in ovarian cancer.
A, B, C, E) These drugs are not used to treat ovarian cancer.

Answer: A
For many years chlorambucil (with of without prednisone) has been the standard treatment of chronic
lymphocytic leukemia. Recently comparisons of fludarabine with chlorambucil has demonstrated that
fludarabine improves progression-free survival, but not overall survival Chlorambucil, a nitrogen mustard,
belongs to the class of alkylating agents. These drugs act by intramolecular cyclization, to form either an
ethyleneimonium or a carbonium ion which are strongly electrophile (i.e. electron attracting). These
intermediates can alkylate, that is can transfer alkyl groups, to various cellular constituents by formation
of covalent bonds with nucleophile (i.e. electron donor) groups of these constituents. Alkylation of
guanine of a single strand of the DNA molecule results in miscoding or in depurination by excision of
guanine residues. Alkylation of guanine of both strands of the DNA molecule results in cross-linking,
which appears to be of major importance to the cytotoxic action of alkylating agents.
B) This is the mechanisms of action of cytarabine
C) This is the mechanisms of action of fluorouracil
D) This is the mechanisms of action of topoisomerase inhibitors
E) This is the mechanisms of action of Vinca alkaloids

Answer: D
The decrease of peripheral blood cells after cancer chemotherapy depends upon the life span of that cell
line. The life span of granulocytes, once released from the bone marrow, is 4-5 hours in the blood and
another 4-5 days in the tissues. Platelets survive about 10 days. Therefore myelosuppression first results
in granulocytopenia followed by thrombocytopenia
A) Lymphocytes continually circulate throughout the body and have life spans of weeks, months or even
years.
B) (See explanation above)
C) Monocytes, once in the tissues, become macrophages and can live for months or even years.
E) Erythrocytes have a life span of about 120 days

Answer: D
The blood exam and the bone marrow biopsy are consistent with the diagnosis of acute myelogenous
leukemia. This leukemia primarily affects adults (the incidence increases with age) and is characterized
by the neoplastic proliferation of myeloblasts. This leukemia primarily affects adults (the incidence
increases with age) and is characterized by the neoplastic proliferation of myeloblasts. The single most
active agent for acute myeloid leukemia is cytarabine. For remission therapy cytarabine is currently used
together with an anthracycline (idarubicin or daunorubicin).
A, B, C, E) These drugs are not currently used in the remission therapy of acute myelogenous leukemia