Cytotoxic Drugs Flashcards
Cytotoxic drugs have both ______________ activity and the potential to damage normal tissue; most cytotoxic drugs are ______________
anti-cancer
teratogenic
- All cytotoxic drugs cause side-effects and a balance has to be struck between likely benefit and acceptable toxicity
Chemotherapy (cytotoxic drugs) may be given with a _____________ intent or it may aim to _______________ or to _____________
curative
prolong life
palliate symptoms
What is neoadjuvant therapy?
initial chemotherapy aimed at shrinking the primary tumour, thereby rendering local therapy less destructive or more effective
What is adjuvant treatment?
follows definitive treatment of the primary disease when the risk of subclinical metastatic disease is known to be high
Cytotoxic drugs fall into a number of classes, each with characteristic _______________ activity, _______________, and ______________. A knowledge of sites of metabolism and excretion is important because impaired drug handling as a result of disease is not uncommon and may result in enhanced toxicity
antitumour
sites of action
toxicity
Many side-effects of cytotoxic drugs often do not occur at the time of administration, but _____________ later
days or weeks
- It is therefore important that patients and healthcare professionals can identify symptoms that cause concern and can contact an expert for advice
A number of cytotoxic drugs will cause severe local tissue necrosis if ____________________ occurs
leakage into the extravascular compartment
*To reduce the risk of extravasation injury it is recommended that cytotoxic drugs are administered by appropriately trained staff
A sore ________________ is a common complication of cancer chemotherapy; it is most often associated with fluorouracil, methotrexate, and the anthracyclines
mouth (oral mucositis)
Oral mucositis is most often associated with which cytotoxic drugs? (3)
- Fluorouracil
- MTX
- Anthracyclines
What measures can be taken to minimize oral mucositis during chemotherapy? (2)
- Rinsing mouth frequently and effective brushing of teeth with a soft brush 2-3 times daily
- For fluorouracil, sucking ice chips during short infusions of the drug is also helpful
* Once a sore mouth has developed, treatment is much less effective
In general, mucositis is self-limiting but with poor oral hygiene it can be a focus for ________________.
blood-borne infection
What is the cause of tumor lysis syndrome?
Spontaneous or treatment-related rapid destruction of malignant cells; pre-existing hyperuricemia, dehydration, and renal impairment are also predisposing factors
Which patients are at risk of tumor lysis syndrome? (5)
- Non-Hodgkin’s lymphoma (especially if high grade and bulky disease)
- Burkitt’s lymphoma
- ALL
- AML (particularly if high white blood cell outs or bulky disease)
- Occasionally those with solid tumors
What are the features of tumor lysis syndrome? (6)
- Hyperkalemia
- Hyperuricemia
- Hyperphosphatemia
- Hypocalcemia
- Renal damage
- Arrhythmias
Hyperuricaemia, which may be present in high-grade _____________ and _____________, can be markedly worsened by chemotherapy and is associated with _______________
lymphoma
leukaemia
acute renal failure
How is hyperuricemia prevented in patients receiving chemotherapy for high grade lymphoma and leukemia? (2)
- Allopurinol started 24 hours before treatment (or febuxostat started 2 days before cytotoxic therapy)
- Adequate hydration
______________, a recombinant urate oxidase, is licensed for hyperuricaemia in patients with haematological malignancy
Rasburicase; It rapidly reduces plasma-uric acid concentration and may be of particular value in preventing complications following treatment of leukaemias or bulky lymphomas.
All cytotoxic drugs except _______________ and _______________ cause bone-marrow suppression
vincristine sulfate
bleomycin
All cytotoxic drugs except vincristine sulfate and bleomycin cause _________________
bone-marrow suppression
_________________ commonly occurs 7 to 10 days after administration, but is delayed for certain drugs, such as carmustine, lomustine, and melphalan.
Bone-marrow suppression
Bone-marrow suppression commonly occurs ________________ after administration, but is delayed for certain drugs, such as carmustine, lomustine, and melphalan.
7 to 10 days
________________ must be checked before each treatment with cytotoxic drugs, and doses should be reduced or therapy delayed if _______________ has not recovered.
Peripheral blood counts
bone-marrow
Cytotoxic drugs may be contra-indicated in patients with acute ______________
Infection
*any infection should be treated before, or when starting, cytotoxic drugs.
Fever in a neutropenic patient (neutrophil count less than 1.06×109/litre) requires __________________
immediate broad-spectrum antibacterial therapy;
Appropriate bacteriological investigations should be conducted as soon as possible
Fever in a neutropenic patient (neutrophil count less than ______________) requires immediate broad-spectrum antibacterial therapy.
1.06×109/litre
Patients taking cytotoxic drugs who have signs or symptoms of ______________ should be advised to seek prompt medical attention.
infection
In selected patients, the duration and the severity of neutropenia can be reduced by the use of ____________________
recombinant human granulocyte-colony stimulating factors
Symptomatic anaemia caused by cytotoxic drugs is usually treated with ____________________
red blood cell transfusions
Reversible _______________ is a common complication of cytotoxic therapy, although it varies in degree between drugs and individual patients. No pharmacological methods of preventing this are available
hair loss
Are there available mechanisms of preventing alopecia secondary to cytotoxic therapy?
No pharmacological methods available
_________________ can be a complication of cancer itself, but chemotherapy increases the risk
Venous thromboembolism
Venous thromboembolism can be a complication of cancer itself, but ______________ increases the risk
chemotherapy
Most cytotoxic drugs are teratogenic and should not be administered during pregnancy, especially during the ________ trimester
first
Are cytotoxic drugs safe to use during pregnancy?
No; teratogenic, especially during the first trimester
- Considerable caution is necessary if a pregnant woman presents with cancer requiring chemotherapy, and specialist advice should always be sought
Exclude ______________ before treatment with cytotoxic drugs
pregnancy
_______________ advice should be given before cytotoxic therapy begins- women of childbearing age should use effective contraception during and after treatment
Contraceptive
Regimens that do not contain an alkylating drug or procarbazine may have ____________ (more/less) effect on fertility
Less
Regimens that do not contain an ____________ drug or _______________ may have less effect on fertility
alkylating
procarbazine
Cytotoxic therapies containing alkylating drugs or procarbazine carry the risk of causing permanent ________________
male sterility (there is no effect on potency); Pretreatment counselling and consideration of sperm storage may be appropriate
Are women more or less affected by the sterilizing effects of alkylating drugs or procarbazine?
Compared to men, women are less severely affected, though the span of reproductive life may be shortened by the onset of premature menopause
Is there an increase in fetal abnormalities or abortion rates recorded in patients who remain fertile after cytotoxic chemotherapy?
No
Nausea and vomiting cause considerable distress to many patients who receive ________________ and to a lesser extent _______________, and may lead to refusal of further treatment
chemotherapy
abdominal radiotherapy
*prophylaxis of nausea and vomiting is therefore extremely important
Nausea and vomiting associated with chemotherapy or abdominal radiotherapy may be ___________ (occurring within 24 hours of treatment), ___________ (first occurring more than 24 hours after treatment), or ____________ (occurring prior to subsequent doses)
acute
delayed
anticipatory
Chemo-related nausea and vomiting: ______________ and ______________ symptoms are more difficult to control than ___________ symptoms and require different management
Delayed
anticipatory
acute
Patients vary in their susceptibility to drug-induced nausea and vomiting; those affected more often include _____________, patients under ___________ years of age, ____________ patients, and those who experience ____________. Susceptibility also increases with repeated exposure to the cytotoxic drug.
women
50
anxious
motion sickness
Which cytotoxic therapies have MILD emetogenic potential? (5)
- Fluorouracil
- Etoposide
- MTX (low dose)
- Vinca alkaloids
- Abdominal radiotherapy
Which cytotoxic therapies have MODERATE emetogenic potential? (5)
- Taxanes
- Doxorubicin
- Cyclophosphamide (intermediate and low dose)
- Mitoxantrone
- MTX (high dose)
Which cytotoxic therapies have HIGH emetogenic potential? (3)
- Cisplatin
- Dacarbazine
- Cyclophosphamide (high dose)
____________ emetogenic treatment: fluorouracil, etoposide, methotrexate (less than 100 mg/m2, low dose in children), the vinca alkaloids, and abdominal radiotherapy.
Mildly
______________ emetogenic treatment: the taxanes, doxorubicin hydrochloride, intermediate and low doses of cyclophosphamide, mitoxantrone, and high doses of methotrexate (0.1– 1.2 g/m2).
Moderately
_______________ emetogenic treatment: cisplatin, dacarbazine, and high doses of cyclophosphamide.
Highly
Prevention of acute symptoms:
For patients at low risk of emesis, pretreatment with ______________ or ______________ may be used.
dexamethasone
lorazepam
Prevention of acute symptoms:
For patients at high risk of emesis, a _______________, usually given by mouth in combination with ______________ and the neurokinin receptor antagonist _____________ is effective.
5HT3-receptor antagonist
dexamethasone
aprepitant
What is the first line drug regimen for prevention of chemo-related nausea in low risk patients?
Pretreatment with:
- Dexamethasone
OR
- Lorazepam
What is the first line drug regimen for prevention of chemo-related nausea in high risk patients?
5HT3-receptor antagonist (eg ondansetron) given orally
+ dexamethasone
+ aprepitant (nerokinin receptor antagonist)
How are delayed symptoms of moderately emetogenic chemotherapy treated?
Dexamethasone + 5HT3-receptor antagonist
How are delayed symptoms of highly emetogenic chemotherapy treated?
Dexamethasone + aprepitant
Rolapitant and metoclopramide are also licensed for delayed chemo-induced N/V
Prevention of anticipatory symptoms related to chemotherapy:
Good _____________ is the best way to prevent anticipatory symptoms. Lorazepam can be helpful for its amnesic, sedative, and anxiolytic effects.
symptom control
Prevention of anticipatory symptoms of chemotherapy:
Good symptom control is the best way to prevent anticipatory symptoms. _______________ can be helpful for its amnesic, sedative, and anxiolytic effects.
Lorazepam
The _______________ cytotoxic drugs are associated with dose-related, cumulative, and potentially life-threatening cardiotoxic side-effects
anthracycline
The anthracycline cytotoxic drugs are associated with dose-related, cumulative, and potentially life-threatening ____________ side-effects
cardiotoxic
______________ is used to counteract the folate-antagonist action of methotrexate and thus speed recovery from methotrexate-induced mucositis or myelosuppression
Folinic acid (given as calcium folinate)
- ‘folinic acid rescue’
_______________ is also used in the management of methotrexate overdose, together with other measures to maintain fluid and electrolyte balance, and to manage possible renal failure
Folinic acid
Does folinic acid counteract the antibacterial activity of folate antagonists such as trimethoprim?
Nope
Folinic acid does not counteract the antibacterial activity of folate antagonists such as ______________
trimethoprim
When folinic acid and fluorouracil are used together in metastatic colorectal cancer the _________________ improves compared to that with fluorouracil alone
response-rate
When folinic acid and ________________ are used together in metastatic colorectal cancer the response-rate improves compared to that with ______________ alone
fluorouracil
fluorouracil
When ______________ and fluorouracil are used together in metastatic colorectal cancer the response-rate improves compared to that with fluorouracil alone
folinic acid
The calcium salt of levofolinic acid, a single isomer of folinic acid, is also used for rescue therapy following methotrexate administration, for cases of methotrexate overdose, and for use with fluorouracil for colorectal cancer. The dose of calcium levofolinate is generally _____________ that of calcium folinate
half
___________________ is a common manifestation of urothelial toxicity which occurs with the oxazaphosphorines, cyclophosphamide and ifosfamide
Haemorrhagic cystitis
Haemorrhagic cystitis is a common manifestation of urothelial toxicity which occurs with the oxazaphosphorines, cyclophosphamide and ifosfamide; it is caused by the metabolite ___________
acrolein
Which cytotoxic drugs are associated with the development of hemorrhagic cystitis? (3)
- Oxazaphosphorines
- Cyclophosphamide
- Ifosfamide
______________ reacts specifically with this acrolein in the urinary tract, preventing hemorrhagic cystitis
Mesna
Mesna is used routinely (preferably by mouth) in patients receiving ____________, and in patients receiving ____________ by the intravenous route at a high dose (e.g. more than 2 g) or in those who experienced urothelial toxicity when given cyclophosphamide previously
ifosfamide
cyclophosphamide
Which drugs are considered cytotoxic antibiotics? (4)
- Daunorubicin
- Doxorubicin
- Epirubicin
- Idarubicin
Many cytotoxic antibiotics (anthracyclines) act as ______________ and simultaneous use of radiotherapy should be avoided because it may markedly increased toxicity
radiomimetics
Many cytotoxic antibiotics (anthracyclines) act as radiomimetics and simultaneous use of _______________ should be avoided because it may markedly increased toxicity
radiotherapy
Doxorubicin hydrochloride is available as both ____________ and ____________ formulations
conventional
liposomal
- The different formulations vary in their licensed indications, pharmacokinetics, dosage and administration, and are NOT interchangeable
What are the indications of conventional doxorubicin? (5)
- Acute leukemias
- Hodgkin’s lymphoma
- Non-Hodgkin’s lymphoma
- Pediatric malignancies
- Some solid tumors including breast cancer
Epirubicin hydrochloride is structurally related to doxorubicin hydrochloride and can be used to treat ____________ cancer
breast
Epirubicin hydrochloride is structurally related to _______________ and can be used to treat breast cancer
doxorubicin hydrochloride
Idarubicin hydrochloride has general properties similar to those of _______________; it is mostly used in the treatment of haematological malignancies
doxorubicin hydrochloride
Idarubicin hydrochloride has general properties similar to those of doxorubicin hydrochloride; it is mostly used in the treatment of _______________
haematological malignancies
Daunorubicin also has general properties similar to those of ______________
doxorubicin hydrochloride
Bleomycin is given ____________ or ___________ to treat metastatic germ cell cancer and, in some regimens, non-Hodgkin’s lymphoma
intravenously
intramuscularly
Bleomycin is given intravenously or intramuscularly to treat ______________ cancer and, in some regimens, ______________
metastatic germ cell
non-Hodgkin’s lymphoma
Dactinomycin is principally used to treat ____________ cancers. Its side-effects are similar to those of doxorubicin, except that cardiac toxicity is not a problem
paediatric
Dactinomycin is principally used to treat paediatric cancers. Its side-effects are similar to those of doxorubicin, except that _______________ toxicity is not a problem
cardiac
What are the indications for mitomycin? (5)
- Gastrointestinal cancer
- Breast cancer
- Non-small cell lung cancer
- Metastatic pancreatic cancers
- Bladder tumors (superficial)
(All IV except bladder tumors which are administered via bladder instillation_
Mitomycin causes delayed _______________ toxicity
Bone marrow
Which drugs are in the class of vinca alkaloids? (4)
- Vinblastine
- Vincristine
- Vindesine
- Vinorelbine (semi-synthetic)
Vinca alkaloids are used to treat which cancers? (4)
- Leukemias
- Lymphomas
- Some solid tumors
- Vinorelbine also used to treat breast cancer
What is the mechanism of action of anti metabolites?
Antimetabolites are incorporated into new nuclear material or combine irreversibly with cellular enzymes, preventing normal cellular division
Which drugs fall in the class of alkylating drugs? (7)
- Cyclophosphamide
- Ifosfamide
- Melphalan
- Lomustine
- Carmustine
- Estramustine
- Mitobrornitol
What is the mechanism of action of alkylating drugs?
Damage DNA, thus interfering with cell replication
Cyclophosphamide is used mainly in combination with other agents for treating a wide range of malignancies, including some ______________, ____________, and _____________
leukaemias
lymphomas
solid tumours
Cyclophosphamide is given ___________ or ____________; it is inactive until metabolized by the ____________
Orally
Intravenously
Liver
____________ is licensed for the treatment of multiple myeloma, polycythaemia vera, childhood neuroblastoma, advanced ovarian adenocarcinoma, and advanced breast cancer
Melphalan
- However, in practice, melphalan is rarely used for ovarian adenocarcinoma; it is no longer used for advanced breast cancer
What are the indications of melphalan? (5)
- MM
- PCV
- Childhood neuroblastoma
- Advanced ovarian adenocarcinoma (rarely used)
- Advanced breast cancer (no longer used)
_______________ implants are licensed for intralesional use in adults for the treatment of recurrent glioblastoma multiforme as an adjunct to surgery
Carmustine
Carmustine implants are also licensed for high-grade ______________ as adjunctive treatment to surgery and radiotherapy
malignant glioma
Estramustine phosphate is a combination of an _______________ and _____________ used predominantly in prostate cancer
oestrogen
chlormethine
Estramustine phosphate is a combination of an oestrogen and chlormethine used predominantly in ______________ cancer
prostate
_______________ is a combination of an oestrogen and chlormethine used predominantly in prostate cancer
Estramustine phosphate
