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Canine Chemotherapy Drugs
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Chemotherapy treads
a narrow path between effectiveness and toxicity. In fact, chemotherapeutic
protocols are most often limited not by the ability of drugs to kill tumor
cells, but by their toxicity to the patient. The goal is to destroy as many
malignant cells as possible while leaving enough normal, "organized" cells
to recover organ function. It is important, therefore, that we use the highest
dosages that we think the patient can tolerate. The more cancer cells surviving
any one time, the sooner the patient will become resistant to the beneficial
effects of the drugs.
Risks to People Living with
Chemotherapy-treated Pets
The anti-cancer drugs are excreted from the animal's body via urine and
feces. This usually happens in the 48 hours following treatment, but can
be as long as 5 days for Adriamycin. If it is possible, you should try to
have the animal eliminate in an area away from the immediate yard or play
area. Cat boxes should be changed regularly, and waste material handled with
a scoop. If urine or feces must be handled, use heavy rubber or latex gloves
and disposable wipes/towels. Place all waste/towels in a plastic bag and
seal it, before disposal. Smooth surfaces may be washed with a dilute bleach
solution (1/4 c. to 1 gallon of water). Humans and other household pets living
with treated pets are generally thought not to be at any health risk, just
as in the case with humans. Pregnant women should not handle ANY animal waste
or anti-cancer medications. If any family member living with the pet has
a condition that would suppress his/her immune system, it would be prudent
to let the veterinarian know.
source:http://www.portlandvetspecialists.com/library/cancer7.html
Chemotherapy
Basic Information for Pet
Owners
Chemotherapy refers to any drug given for therapeutic reasons. Technically,
antibiotics are chemotherapy. However, common use has changed the term
to refer almost exclusively to treating cancer. In this context, chemotherapeutic
agents (chemotherapy drugs) are those that kill cancer cells. The best
chemotherapy drugs are those that kill only cancer cells, and leave normal
body cells alone. Unfortunately, these drugs are rare to non-existent. There
are always civilian casualties' in the was against cancer.
Chemotherapy is the single most effective method of treatment for some
cancers (like lymphoma or lymphosarcoma) and offers an opportunity for
extension of life along with good quality of life during therapy. We will
also recommend chemotherapy after surgical removal of some tumors. There
are two reasons for this: to stop the recurrence of the tumor in the same
location, and to inhibit its spread to distant parts of the body (a process
called metastasis). Although we do not offer radiation therapy at our clinic,
chemotherapy is sometimes used in conjunction with radiation in order to
make the radiation more effective at killing the cancer cells.
Cancer cells tend to be rapidly replicating (reproducing), which is why
cancers spread so quickly, and why tumors can grow so rapidly. The drugs
used to treat cancers affect rapidly growing cells the most. They are often
drugs that interfere with the cell's DNA, and so kill the cell when it tries
to divide. In order to be effective, these drugs need dividing cells like
those present in tumors.
The collateral' damage happens mostly to other rapidly dividing cells
in the body like the bone marrow and the lining of the stomach and intestines.
These cells are the ones hardest hit by chemotherapy drugs, and the effect
on these cells are what cause the problems we associate most with chemotherapy.
Side effects
The most common adverse effects of chemotherapy are on the gastrointestinal
tract. We typically see nausea, vomiting, and possibly diarrhea. Because
most animals are not good at telling their owners that they feel nauseated,
and because most owners are unaware of the subtle signs of nausea, we usually
dispense an anti-nausea medication that is given at home for a day or two
after each chemotherapy treatment. We give it to patients in the hope of
forestalling any vomiting, or helping if the pet does experience nausea.
A few key signs of nausea are lip-licking, drooling, and lack of appetite.
The most serious effect of chemotherapy drugs is their effect on the
rapidly dividing cells of the bone marrow. The marrow contains undifferentiated
blood cells that will develop into the many different cells that populate
normal blood. We are concerned mostly with the cells that are the "parents"
of the white blood cells. White blood cells fight infection, and a serious
depletion in their numbers, as can happen when the bone marrow is affected
by chemotherapy drugs, can leave the pet vulnerable to serious infection.
Sometimes this infection can become systemic and enter the bloodstream, a
condition called sepsis. Sepsis is a potentially life-threatening condition.
A much less common problem is hair loss. Few dogs experience real hair
loss when undergoing chemotherapy. The exception to this is a breed with
continuously growing hair, like the Lhasa Apso, Poodle, Shih Tzu, Old English
Sheepdog, Puli, Maltese, and some Schnauzers. We will sometimes see significant
hair loss in these dogs early on in the treatment protocol. This hair will
grow back once chemotherapy stops, or even when the frequency of drug administration
is decreased. Also, not all dogs of these breeds experiences hair loss;
it is an individual thing.
An additional adverse reaction that can occur with some types of chemotherapy
drugs is an extreme tissue reaction to the drug if it accidentally comes
in contact with the tissues around or outside of a vein. If the drugs leak
out of the vein, or are accidentally injected outside of the vein, severe
necrosis (death) of the surrounding tissue can occur. Needless to say, this
is a very infrequent occurrence as every precaution is take to prevent it,
including using long intravenous catheters and sedating pets who are at
risk of dislodging a catheter during chemotherapy administration. The drugs
most commonly associated with this tissue reaction are doxorubicin, vincristine,
and nitrogen mustard.
Other side effects are quite drug-specific.
Doxorubicin treatment carries with it a risk of cardiotoxicity (heart
damage).
The platinum agents (cisplatin and carboplatin) can be very toxic to
the kidneys.
Cyclophosphamide can cause sterile cystitis (bladder inflammation).
Vinca alkaloids (vincristine, vinblastine) and platinum agents can be
neurotoxic.
L-asparaginase and many other drugs can cause acute allergic and hypersensitivity
reactions.
CCNU (Lomustine) and other drugs. can be toxic to the liver.
Monitoring
All patients undergoing chemotherapy will need regular blood testing.
The majority of the tests will be checks of the blood cell counts. We will
also need to evaluate the liver and kidneys on a regular basis ("regular"
depending on the type of protocol being used). As a rule of thumb, blood
counts are done 7-10 days after the dose of chemotherapeutic drug. There
are variations on this, and you will be informed of the schedule for your
pet before we start his or her treatment.
Quality of Life
Chemotherapy is meant to prolong life, not to prolong dying.
It is not cruel or inhumane to opt for cancer chemotherapy for your pet.
Most animals that undergo chemotherapy have a very good quality of life.
They are happy, eating and drinking, and interacting with their families.
Most have normal energy levels most of the time. There may be a day or two
right after the chemotherapy treatment day where the pet feels "off", but
we try to minimize any of the detrimental chemotherapy effects as much as
we can. Also, we can stop at any time. If you, the pet's owner, feel that
his or her quality of life is poor during chemotherapy we can stop giving
the drugs. Many owners enter into chemotherapy with some trepidation, and
discover that the reality is nowhere near as bad as their expectations.
The Cure
Cancers are rarely cured. In most cases we hope for remission of the
tumor, or remission of the cancer effects that are making the pet feel
sick. Some cancer types offer the hope of long remission times, but there
are always variations.
We have to face the sad reality that most pets who have cancer, even
if they have chemotherapy, will eventually relapse. We will be faced with
the decision of when and whether to euthanize. As always, this decision
should be made by loving owners based on their knowledge of their own pet,
and with his or her quality of life always in mind.
Pain management
Many clients are concerned that their pets are experiencing pain with
their cancer. Control of pain is one of our top priorities, not only from
a humane aspect but because animals in pain do not respond as well to therapy
and do not heal as well.
We work with all of our clients to optimize pain relief for their pets
and minimize discomfort.
Nutrition
Cancer patients need to eat to stay strong and have the resources to
handle chemotherapy and the effects of the cancer. We encourage all owners
to encourage their pets to eat. Warming the food and providing a stimulating
environment is sometimes all that is required. For other patients, the
best was to get nutrition in is via a feeding tube. These can be minimally
invasive and extremely well tolerated. Sometimes appetite stimulants will
help. Supplemental amino acids, omega-3 fatty acids and a good vitamin and
mineral supplement (such as Canine Plus) also assist in the patient's recovery.
The Practicalities
Most chemotherapy drugs are given by intravenous injection or infusion
through an intravenous catheter. This means that an intravenous catheter
is placed and secured. The chemotherapy drug is injected through the catheter
with a syringe, followed by a copious flushing with saline. Drugs that take
longer to infuse (like doxorubicin) will be delivered via a regular intravenous
drip over a period of time.
Depending on the drug (and that can vary by the week in some chemotherapy
protocols) you should plan on the entire visit taking about 30-45 minutes
(for injections or rapid infusions) or up to 3 hours for longer infusions
(typically doxorubicin). You will be informed of the appointment length
when you book.
The cost of the treatments will depend on the medications. Chemotherapy
drug costs vary wildly, from $20 (£10.00 approx.) per treatment to
$750, (£375.00 approx) depending on the drug and the size of the patient.
There are also attendant costs for the actual procedure, whether it involves
an IV catheter and injection or a full intravenous setup. You will be informed
of the cost, if you so desire, before starting any chemotherapy protocol.
Chemotherapy can last anywhere from a few weeks to several months to
lifelong, depending on the type of cancer being treated and the therapy
protocol used.
Emergencies
It is always a good idea that you keep a diary of your pet's chemotherapy
treatment. Noting the dates and drugs used for each session, as well as
the dates of follow up lab testing is very useful to anyone treating your pet in an emergency. Also have
a written record of any oral medications you may be prescribed, their doses and frequency.
Some emergencies can be directly attributable to the chemotherapy treatment.
Sometimes you just have "regular" emergencies. In either case the veterinarian
seeing your pet will need to know his history in order to treat appropriately
and choose medications that will not interfere or worsen the effects of
the chemotherapy.
Take the bottles of any medications that have been prescribed for your
pet with you when you go to the emergency clinic.
reprinted
with kind permission from Animal Medical Hospital
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Chemotherapy Drugs
Please understand
the following information is offered as a courtesy and is not intended
to provide a diagnosis or medical recommendation for your pet.
Chemotherapy is a word that creates an instant emotional response in
everyone. The treatment of cancer with medication (as opposed to surgery
or radiation) is especially helpful when the cancer in question is not localized
to one body area. Using medication allows the body's blood vessels to carry
the medication even to remote or otherwise inaccessible areas. This form
of treatment is called chemotherapy. Chances are that you, or someone you
know, has experienced chemotherapy for the treatment of cancer. The reality
of chemotherapy for animals is generally different from that for human cancer
patients. Most people are pleasantly surprised at how well their pets feel
while undergoing chemotherapy.
In order for chemotherapy to be effective, the medications must destroy
tumor cells and spare the normal body cells that may be adjacent. This
is accomplished by using medications that affect cell activities that occur
predominantly in cancer cells but not in normal cells. Most chemotherapy
agents focus on the rapid cell division that characterizes the spread
of cancer cells.
Adriamycin
Adriamycin is the most potent
of the agents and can lower the white blood cell count and nausea and vomiting,
and or diarrhea can occur. If the signs are mild, use "adult dose" Pepto
Bismol for dogs >40lbs and "childrens dose" for dogs <40lbs. Moderate
to severe illness requires veterinary intervention. If there is irritation
at the injection sites, notify the doctor. Long-term effects can involve
the heart, but protocols have been calculated to lower this risk. If
your pet gets ill about 1 week after therapy, follow the instructions on
the owner's sheet.
(Doxorubicin
Rubex)
Adriamycin® is a type of anti-cancer drug called an anthracycline
glycoside. Adriamycin (doxorubicin) is a broadspectrum chemotherapy
drug used to fight many forms of cancer and has been used for decades. It
works by impairing DNA synthesis, a crucial feature of cell division, and
thus is able to target rapidly dividing cells. Adriamycin is a very
serious anti-cancer medication with definite potential to do great harm
as well as great good. It is used alone or in combination with other chemotherapy
drugs. It is important to understand its pitfalls and know what sort of
monitoring goes with its use.
Adriamycin® is most commonly used in the treatment of lymphoma,
osteosarcoma and other sarcomas, carcinomas, and melanoma. Adriamycin
is the most widely used anti-cancer drug in small animal practice.
Adriamycin® is an orange red liquid, which is diluted and painlessly
administered directly into a vein. The slow intravenous administration of
Adriamycin usually takes about 15 to 20 minutes. The patient lies quietly
on a padded table during administration and rarely needs any form of sedation.
Adriamycin® is usually administered once every three weeks for a total
of five treatments, but it also may be given in combination with other medications.
Urine will look especially orange for a day or two post-administration.
Owners should avoid handling this urine.
How this Medication is Used
Adriamycin is given only as an intravenous injectable. It is given
slowly over a 10 minute or so period in an IV drip rather than as a single
quick shot. It is very irritating to the skin so that those who work with
it must wear gloves, gowns and protective goggles or masks.
If the injection does not go intravenously and some doxorubicin leaks
into the tissue surrounding the vein, an extreme reaction occurs in the
tissue. (This can happen if multiple attempts at catheterizing the vein
leave some leakage points in the vein, or if the pet chews the catheter
part way out during the administration.) The tissue in contact with the Adriamycin
will die and rot away, leaving a large unhealing wound. Because of the DNA-poisoning
nature of doxorubicin, this wound may actually expand or may simply not
heal. Amputation may be required.
If the tissue exposure is treated immediately with special flushes and
cortisones and special wraps, this disaster has a chance of being averted.
In general, a well-seated IV line is a priority when doxorubicin is administered.
Acute allergic reactions (causing facial swelling, hives, vomiting,
and possibly heart rhythm problems) are common enough that most patients
are pretreated with diphenhydramine, a common antihistamine, to block any
such reaction.
Side Effects
Practically all anticancer drugs have side effects. However, their potential
effect against the cancer generally outweighs the possible side effects.
Although serious adverse effects can occur with any chemotherapy, there
is less than a 5% chance that your pet will be hospitalized with side effects
and less than 1-2% chance of fatality.
Because Adriamycin attacks rapidly dividing cells it is also toxic
to some normal cells: hair follicle cells, bone marrow cells, and intestinal
cells. It is also toxic to muscle cells, particularly heart muscle cells.
Adriamycin is famous for "cumulative cardiotoxicity." This means
that there is a maximum amount of Adriamycin a patient can take during
its lifetime before its heart will be poisoned. The heart dilates, becomes
incapable of effective pumping, and does not respond to therapy. This obviously
is a side effect that must be avoided, which means that the total number
of doxorubicin treatments is limited no matter what the cancer is doing.
The total dose of Adriamycin widely held to be the "ceiling" is 240
mg/M2 (M2 = square meters of body surface area, a more accurate form of dosing
than going by weight) but toxicity can be seen at small levels. Many oncologists
will ultrasound the patient's heart to assess function prior to delivering
a dose of Adriamycin.
Bone marrow toxicities are common with most chemotherapy drugs as this
is one of the areas where the body normally has many rapidly dividing cells.
Red blood cells, which carry oxygen and remove carbon dioxide, are made
here. The white blood cells that make up our immune systems are born here.
The platelets that allow our blood to clot also arise here. Usually it is
the white cells and platelets that are most vulnerable. Monitoring tests are
needed because if a line of cells becomes suppressed, the oncologist may
need to postpone a drug dose, modify a dose, or change to another treatment
to make up for the missing blood cells.
Hair Loss (Alopecia)
When a person loses hair as a result of chemotherapy, it can be emtoionally
devastating. Pets rarely lose their hair, and if they do, they are not
bothered by it as much as people are. In most pet animals. hair does not
grow continually throughout their lives like it does in people. Therefore,
hair loss in. pets is rare. Exceptions are certain breeds of dogs, such
as poodles, Old English Sheepdogs and other breeds whose hair grows continually.
In general, if your pet needs to visit a groomer periodically to be clipped,
then your pet may experience some degree of hair loss as a result of chemotherapy.
Please ask your pet's doctor about the possibility of hair loss in your
pet. Patients on Adriamycin. will have trouble growing in fur
over shaved areas. Whiskers are often lost and do not regrow.
Stomach or Intestinal (Gastrointestinal) Discomfort/ Upset stomach
(Nausea)
Many patients experience some form of stomach or intestinal discomfort
two to seven days after a chemotherapy treatment. Medication will be prescribed
to try to prevent or treat the discomfort. Below are listed some steps
you can take at home.
If your pet begins to show any signs of upset stomach (drooling, ‘smacking’
lips) or loss of appetite, administer the metoclopramide your doctor prescribed
for nausea. Offer ice cubes every few hours. After 12 hours, feed your
pet small, frequent meals instead of one large meal. Upset stomachs, generally
short-lived, are not unusual 2 to 5 days after Adriamycin use. Nausea
is usually controlled with medication.
Call your veterinarian
if you have concerns, or if the condition persists for more than 24 hours.
Vomiting
Administer metoclopramide prescribed for vomting/nausea. Do not give
your pet any food for 12 hours. After 12 hours, offer your pet ice cubes
then small bland meals.
Call your veterinarian
if you have concerns, or if the condition persists for more than 24 hours
Loss of Appetite
If your pet begins to show any signs of upset stomach or loss of appetite,
administer the metoclopramide your doctor prescribed for nausea. Offer
your pet four small meals a day. Add warm broth and favorite foods to increase
flavor and appeal.
Diarrhea
If your pet begins to show signs of diarrhea, administer the medicine
your doctor prescribed for diarrhea. Keep water available at all times.
If your pet is also not eating, offer chicken or beef broth. You may give
Pepto Bismol® (dogs only), 1 tablespoon per 10 pounds of body weight
every 4 to 6 hours.
Call your veterinarian
if you have concerns, or if the condition persists for more than 24 hours.
Reduction in the Number of White Blood Cells (Neutropenia)
There are various types of cells in the blood. The decrease in the number
of infection fighting white blood cells is known as neutropenia. Many
chemotherapeutic agents impair the bone marrow's ability to produce cells.
As a result, neutropenia may occur seven to ten days after chemotherapy.
Neutropenia, alone, is not a danger to your pet. However, your pet's ability
to fight off infection is impaired by neutropenia. Your pet is given a complete
physical, and a blood test called a complete blond count (CBC) is performed
prior to each Adriamycin administration and one week following each injection.
Should your pet have a significant reduction in the number of white blood
cells, your veterinarian may wish to perform periodic blood tests, and/or
prescribe antibiotics to protect your pet from infection.
Tissue Damage
If Adriamycin®, is accidentally given outside the vein, severe tissue
reactions can result. Therefore, Adriamycin is handled with the utmost care,
and is only administered by highly trained professionals. If irritation
of the injection site develops in the form of pain or redness, apply ice
packs for 15 minutes every three hours. Call your veterinarian if you have
concerns, and certainly if the condition persists for more than 24 hours.
Allergic Reactions
Allergic reaction to chemotherapeutic agents is rare, and not a problem
you will have to treat at home. Should your pet have an allergic reaction
to Adriamycin®, it would develop upon administration, and your vet
is trained to treat patients for allergic reaction.
Heart Damage
Adriamycin®, in some rare cases, can irreversibly damage the heart
muscle. The dose of Adriamycin® prescribed for your pet is below the
dose that usually causes heart disease. Less than 10% of our patients develop
heart disease as a result of Adriamycin® chemotherapy. Your veterinarian
will discontinue the use of Adriamycin® if heart disease is detected
at any time.
Interactions With Other
Drugs
Cyclophosphamide, another prominent anticancer drug, has a potential
side effect called hemorrhagic cystitis, where the urine becomes bloody.
This side effect becomes more likely when cyclophosphamide is used with Adriamycin.
Concurrent use of cyclophosphamide may increase the likelihood of Adriamycin-induced
cardiotoxicity, as described above.
Concerns And Cautions
Adriamycin is activated by the patient's liver. A patient with
liver disease may not be able to activate this drug and may not respond
as well. Dosage adjustments are needed for these patients.
The Boxer, Doberman pinscher, and Great Dane are all predisposed genetically
to dilative cardiomyopathy. They may be particularly vulnerable to the cardiotoxicity
side effect of Adriamycin and must carefully screened and monitored.
Adriamycin absolutely cannot be used safely in pregnancy.
It is important to make an appointment for each chemotherapy administration
and the visit for the blood test one week after the Adriamycin® adminsitration.
This medication is given as series of 5 treatments, one treatment every
third week. A CBC will be checked one week after each treatment to assure
that the white blood cell count is not becoming too low.
At each visit, a doctor or an nurse will admit your pet. We work as
a team to minimize the time you and your pet will spend at the hospital.
This team approach maximizes quality care. This may mean you might not
see the same veterinarian or nurse each time, but the intent is to provide
the most comprehensive and compassionate care possible. You will be asked
to fill out a form describing how your pet has been doing since the last
visit; this makes sure your pet’s doctor is aware of even te smallest concern.
This is a good time to express questions you have about your pet's condition..
Your pet will receive a complete physical examination by a doctor, and
blood will be drawn for a complete blood count.
Once the blood values have been reviewed, and are determined to be within
normal limits, your pet will receive an Adriamycin® treatment. This
entire process usually takes two to three treatments.
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Vincristine
Vincristine has little tendency
to make an animal ill. Occasionally, there will be 1 or 2 episodes of "innocuous"
vomiting 24 hours after the injection, which disappears without treatment.
More commonly in people and cats than in dogs, Vincristine can cause intestinal
cramps or constipation. The pet may seem "restless" 24-48 hours after administration.
We have found that over-the-counter Imodium A-D works well in dogs ("adult
dose" for dogs >40lbs; "childrens dose" if <40lbs). For cats, use
any standard hairball laxative or add _ tsp of Metamucil to daily feedings.
It is very irritating to the surrounding tissues if it leaks from the vein
at the injection site. If you notice any inflammation where the injection
was given, notify the doctor.
Brand Names:
Oncovin, Vincasar
Available as Injectable
Background
Because they are transported everywhere that the bloodstream can take
them, drugs of cancer chemotherapy have the ability to reach tumors that
are inaccessible to the surgeon and undetectable to the diagnostician. In
order to spare the normal cells of the body, anti-cancer drugs must affect
activities that cancer cells are involved in but normal cells are not. Since
cancer cells divide rapidly and uncontrollably while normal cells divide
more slowly and in response to controlled cellular messages, most anti-cancer
drugs target cell division.
As a cell divides, microscopic protein rods called microtubules pull
the two cell halves apart. These important structural proteins must be
functional or cell division cannot occur. Vincristine is a member of the
vinca alkaloid class of chemotherapy drugs. It is extracted from the Vinca
rosea plant and is a microtubule poison.
How This Medication Is Used
Vincristine is chiefly used as one drug in multi-drug combination protocols
against lymphoid and round cell tumors. Lymophoma in cats, lymphoma in
dogs, mast cell tumors, and transmissible venereal tumorsoften include
vincristine in their protocols.
Separate from its chemotherapy use, vincristine has the unexplained ability
to cause a sudden release of platelets (blood clotting cells) from the
bone marrow. For this reason, vincristine is commonly included in treatment
of immune-mediated thrombocytopenia (IMT). There has been some controversy
about whether these platelets are as functional as normal ones but current
published protocols for this condition suggest vincristine should be used.
Vincristine is typically utilized as a weekly injection.
Side Effects
Vincristine absolutely must be given intravenously. Vincristine is highly
irritating to the soft tissues and if it is not given intravenously, where
the bloodstream rapidly carries it away and dilutes it within the body's
blood volume, it will cause what is called a tissue slough. This means the
soft tissues will die and fall away leaving a large sore. Unlike the tissue
sloughs of Adriamycin, a vincristine slough will eventually heal but while
it is present, it will require bandaging and be a source of discomfort.
Vincristine has some potential for neurologic side effects, especially
in cats. A neurologically based constipation may result. Difficulty coordinating
the feet may be seen. Humans report paresthesias, which include odd sensations
such as occur when one's foot is "asleep."
Vincristine use will increase blood uric acid levels, rarely a concern
in animals.
Interactions With Other Drugs
The neurologic toxicities noted above are more likely to occur when vincristine
is used in combination with L-Asparaginase, not an uncommon combination
in the treatment of lymphoma.
Concerns And Cautions
Vincristine is not able to pass through the blood/brain barrier and thus
cannot treat tumors in the nervous system.
Vincristine is removed from the body by the liver. If poor liver function
is present, a dose-adjustment may be needed or a different drug selected.
Vincristine should not be used during pregnancy and may cause sterility
in males.
Copyright 2004 - 2008 by Wendy Brooks,
DVM. Used with permission. All rights reserved.
This work was originally published by Veterinary
Information
Network, Inc. (VIN) and is republished with VIN's permission
*****************
Lomustine
Lomustine (Ceenu¨) is also
an oral alkylating agent related to Cytoxan and Leukeran. While most pets
tolerate this versatile drug, significant decreases in cell counts can occur
and the CBC must be monitored closely.
Also known as CCNU
Brand name: CEENU
Available in 10 mg and 100 mg tablets and as injectable
Background
The basic idea behind drugs for cancer chemotherapy is for them to reach
areas of the body inaccessible to surgery and to kill only the cancer cells
leaving the normal cells of the body alone. Cancer cells are involved in
activities such as rapid cell division that normal cells are not, and these
activities make them vulnerable to certain drugs. Lomustine is a member
of the nitrosourea class of chemotherapy agents that act by binding DNA
to other DNA strands or to protein in such a way that the DNA double helix
strand cannot replicate. In addition to essentially tying DNA up, lomustine
generates a by-product that prevents normal DNA function. Remember that DNA
is the instruction manual for the cell. Continuing the analogy, lomustine
makes the pages unreadable and unturnable.
How this Medication Is Used
Lomustine has the special ability to penetrate the blood/brain barrier,
which means it can be used to treat cancers of the nervous system.
The usual tumors against which lomustine is most commonly used are: lymphoma
(particularly cutaneous [skin] lymphoma), mast cell tumors, brain tumors,
kidney tumors, lung tumors, melanoma, and histiocytic sarcoma/malignant
histiocytosis tumors.
Lomustine can be given either orally or intravenously, as the chemotherapy
protocol dictates, generally once a month.
Side Effects
Because lomustine targets rapidly dividing cells, the cells of the bone
marrow are vulnerable whether or not there is cancer present. The bone marrow
is where blood cells are produced and special attention is generally paid
to the white blood cells whose numbers typically drop about a week after
lomustine is given. Often antibiotics are given during the week where the
white count drops to at least partially make up for the blow to the immune
system caused by the drug. Platelets, cells involved in blood clotting, also
drop in number with lomustine but generally recover by the time for the next
dose. If they have not, the dose is generally delayed. Bone marrow effects
are more pronounced in cats, thus lower doses of lomustine are typically used.
Lomustine is harsh on the patient's liver as well. Liver disease first
manifests as a change in lab testing, long (average of 10 weeks) before
the patient actually feels ill. In one study, 7 out of 12 dogs with lomustine-related
liver disease died and the ones that recovered had fewer lomustine doses.
To prevent a patient from developing serious liver disease, an enzyme called
alanine aminotransferase (ALT) is monitored before each lomustine dose.
If there is any elevation, the lomustine treatments are discontinued. No
information is available regarding liver toxicity in cats on lomustine so
currently the canine monitoring protocols are recommended for both species.
Kidney damage from lomustine is not common but is usually included in
the monitoring.
Normal intestinal cells are also rapidly dividing and most chemotherapy
agents targeting rapid cell division generally cause an upset stomach. Lomustine
does not, which poses a tremendous advantage of this drug over others,
at least from the patient's perspective.
Interactions with Other Drugs
Lomustine is removed from the body by the liver's detoxification processes
within hours of administration. Phenobarbital, the most common oral anti-convulsant
in pets, enhances the enzymes involved, which means that pets on phenobarbital
remove lomustine from their bodies faster than they normally would and
lomustine will not work as well.
Copyright 2004 - 2008 by the Veterinary Information
Network, Inc. All rights reserved.
This work was originally published by Veterinary
Information
Network, Inc. (VIN) and is republished with VIN's permission
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Cyclophosphamide (Cytoxan)
Cyclophosphamide is a potent
chemotherapeutic agent and can lower the white blood cell count about 7
days after it is given. Mild to moderate nausea can occur. The tablets should
be given in the morning (all at once with food), and the pet should be given
ample opportunity to empty his bladder throughout the day. Occasionally,
bloody urine can occur due to direct bladder effects. This drug is often
given with a diuretic (lasix or furosemide) to speed its excretion from the
body. If your pet should get sick about 1 week post treatment, follow the
instructions on the owner Õs sheet given at the start of treatment.
The caregiver should wear disposable gloves while handling the tablets.
Brand Name: Cytoxan
Available as 25 mg and 50 mg tablets
How This Medication Works
Cyclophosphamide is a serious drug used to treat very serious disease.
One uses cyclophosphamide to kill cells that are causing harm, usually
cancer cells or inflammatory cells.
This potent cell-killing medication is a nitrogen mustard derivative,
meaning it is related to the toxic chemical weapon mustard gas (so named
because of its mustard or horseradish odor) used widely in World War I. In
chemotherapy, cyclophosphamide is classified as an alkylating agent, which
means it works by binding to DNA and interfering with normal cell function.
By disrupting cellular DNA, cyclophosphamide is able to kill the cell. Cells
that divide rapidly (and thus replicate their DNA rapidly) are especially
targeted by cyclophosphamide. This makes cyclophosphamide especially able
to kill:
Rapidly dividing cancer cells
Bone marrow cells such as developing blood cells
Stimulated lymphocytes (those engaged in proliferation and antibody production)
Fetal cells
Hair follicle cells
Intestinal cells
Uses of this Medication
Because of its ability to kill rapidly dividing cells, cyclophosphamide
has been used most successfully in two situations:
Immune mediated diseases (especially those of life-threatening nature
such as immune mediated hemolytic anemia)
Cancer chemotherapy (especially for bone marrow or blood cell cancers
such as lymphoma)
Side Effects
There are several important side effects to consider when using cyclophosphamide:
Bone Marrow Suppression
White cell blood lines show suppression (i.e., counts will drop) approximately
1 to 2 weeks following a dose of cyclophosphamide. This time period makes
the patient especially vulnerable to infection. Many oncologists like to
monitor white blood cell count and withhold cyclophosphamide if the white
blood cell count is not greater than a certain minimum number. Other oncologists
do not like to reduce the cyclophosphamide dose without evidence of infection
as reducing the cyclophosphamide dose will give the tumor an advantage
and possibly jeopardize the remission.
Hair Loss
While human chemotherapy patients commonly lose their hair, animal patients
almost never do. The exceptions are wavy coated dogs such as poodles and
Old English sheepdogs. Cats undergoing chemotherapy commonly lose their
whiskers. Hair texture on pets in general tends to get softer on chemotherapy.
Upset Stomach
Despite the image most people have of nausea associated with chemotherapy,
this is actually a surprisingly uncommon problem in dogs and cats. When
it occurs, it is generally readily controllable with antinausea medications.
Development of Hemorrhagic Cystitis
Up to 30% of dogs (depending on the study) receiving cyclophosphamide
for over 2 months develop bloody urine caused by excretion of irritating
cyclophosphamide metabolites. This condition may represent pre-cancer in
it and must be distinguished from a bladder infection. This is a serious
side effect of cyclophosphamide use and any sign of bloody urine should be
reported to the veterinarian at once.
Interactions With Other Drugs
Cyclophosphamide should be avoided in patients taking other bone marrow
suppressing agents (such as azathioprine or methimazole). The effect of two
marrow suppressors is additive.
Phenobarbital will increase the rate of excretion of cyclophosphamide
(i.e., cyclophosphamide will be more rapidly removed from the body). This
will increase the toxicity potential of the cyclophosphamide.
Diuretics of the thiazide class may increase the bone marrow suppression
side effects of cyclophosphamide.
In the treatment of immune mediated disease, it is common and usual to
use cyclophosphamide in conjunction with corticosteroids (such as prednisone
or dexamethasone).
Concerns and Cautions
Obviously it is not prudent to suppress the immune system in the face
of a known infection.
Cyclophosphamide is toxic to the unborn fetus and should not be used
in pregnancy.
The majority of cyclophosphamide is excreted in urine and a dose is still
detectable in urine some 72 hours after administration.
Due to the unique manufacture of cyclophosphamide tablets, these tablets
cannot be accurately dose after being cut. It is best to use tablets whole.
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Network, Inc. All rights reserved.
This work was originally published by Veterinary
Information
Network, Inc. (VIN) and is republished with VIN's permission
**********************
L-Asparaginase
Asparaginase is well tolerated.
In rare instances, it can cause vomiting due to pancreatitis. Since it is
a protein, there is a (rare) possibility that an animal can have an allergic
reaction to it. We would ask that your pet remain in the lobby for about
15 minutes after this injection.
Brand Names: Elspar, Oncaspar, and Erwinase
Available as injectable only
Background
In order to make an effective medication for the treatment of cancer,
some fundamental difference between normal cells and cancer cells must be
defined. The chemotherapy agent must exploit this cellular difference such
that normal cells are spared and only cancer cells are injured. L-asparaginase
works by exploiting the unusually high requirement tumor cells have for the
amino acid asparagine.
Chemical structure for the amino acid asparagine
Asparagine is an amino acid required by cells for the production
of protein. Asparagine can either be produced within a cell through an
enzyme called asparagine synthetase or it can absorbed into the cell from
the outside (i. e., it is consumed in the patient’s diet, absorbed into
the body and made available to the body’s cells. Tumor cells, more specifically
lymphatic tumor cells, require huge amounts of asparagines to keep up with
their rapid, malignant growth. This means they use both asparagine from
the diet as well as what they can make themselves (which is limited) to
satisfy their large asparagine demand.
Normal cells do not require nearly as much asparagine to survive and
are able to make all the asparagine they need internally. On the other
hand, tumor cells become depleted rapidly and die if the dietary supply
is cut off because they cannot manufacture enough internally to support their
continuing growth. The enzyme L-Asparaginase destroys asparagine outside
the cells forcing the cells to rely completely on what they can produce
on their own.
How This Medication Is Used
Mostly this medication is used against lymphoma but it also is used in
some mast cell tumor protocols. Unlikely other chemotherapy agents, it
may be given as an intramuscular, subcutaneous, or intravenous injection
without fear of tissue irritation. This is not a medication that you would
use at home.
Side Effects
Not all normal cells can rely on internally produced asparagine. The
cells of the body that normally reproduce rapidly or engage in heavy protein
synthesis for other purposes may be unable to grow or function normally
in an environment depleted of asparagine. The cells in question are those
of the intestine, bone marrow, liver, and pancreas. While bone marrow suppression
is rarer with this medication than with other chemotherapy agents, there
is still some concern about blood clotting disorders, toxicity to the liver,
diarrhea and/or vomiting, and the development of canine pancreatitis or feline
pancreatitis. Fortunately, in most patients it is well tolerated.
L-asparaginase is an enzyme commercially produced by bacteria. It is
inherently a foreign protein and as such can produce an anaphylactic reaction.
This is a rare complication but pre-treatment with anti-histamines or corticosteroids
may be prudent in some cases.
L-asparaginase may interfere with blood clotting, may raise blood sugar
levels, may raise liver enzyme blood tests, and may cause liver disease in
some patients.
The most common side effect of this medication is vomiting.
Interactions with Other Drugs
Methotrexate is another common anti-tumor drug. L-asparaginase and methotrexate
work against each other and should be administered at least 48 hours apart.
Concurrent use of prednisone or vincristine may increase the toxicity
potential. (L-Asparaginase is commonly used in combination with these drugs).
Concerns and Cautions
When L-asparaginase destroys asparagine, ammonia is a by-product. In
patients with compromised liver function, the transient high levels of
ammonia in the blood could pose a toxic problem. Liver disease does not
preclude the use of L-asparaginase but it is important to watch for symptoms
referable to liver disease (generally neurologic abnormalities/hepatic encephalopathy).
The use of L-asparaginase has been associated with pancreatitis. It is
best not used in patients with a history of pancreatitis.
Copyright 2007 - 2008 by the Veterinary Information
Network, Inc. All rights reserved.
This work was originally published by Veterinary
Information
Network, Inc. (VIN) and is republished with VIN's permission
********************
Cisplatin
(Also called cis-Platinum II, cis-DDP, CDDP, DDP, or cis-diamminedichloroplatinum)
BACKGROUND
Cancer is the condition where a significant number of malignant cells
have defeated the body's natural protective mechanisms and have proliferated.
Malignant cells are dangerous because they have reverted to characteristics
typical of embryonic cells. Instead of doing the jobs that normal cells
of their tissue type are supposed to do, they simply divide rapidly over
and over and ultimately obliterate the normal tissue from whence they came.
Often they invade local lymphatic or blood vessels so as to spread to distant
body areas and set up new cancerous areas far from where they originally
started.
If a group of cancer cells is localized to one area it may be possible
to surgically removed them but treatment is more difficult if they have
spread. For this situation, we need medications that selectively kill cancer
cells and leave normal cells alone. We can use the body's own bloodstream
to carry these medications to all the distant sites where cancer may have
set up. This kind of treatment is called chemotherapy.
Most chemotherapy drugs target the fact that cancer cells are rapidly dividing
and interfere with cell division. It is not known exactly how cisplatin
attacks cancer cells.
HOW THIS MEDICATION IS USED
Cisplatin is used intravenously only. Administration requires a process
called diuresis, which helps protect the patient's kidneys from damage. This
means that your pet will have to be hospitalized on the day of treatment and
receive intravenous fluids.
Tumors for which cisplatin is effective:
Squamous cell carcinoma
Transitional cell carcinoma
Ovarian carcinoma
Mediastinal carcinoma
Osteosarcoma
Nasal carcinoma
Thyroid carcinoma
SIDE EFFECTS
Nausea beginning 6 hours after treatment and persisting for another 6 hours
is expected with use of cisplatin.
Cisplatin can cause kidney damage. Monitoring blood tests are done regularly
so that therapy can be modified should kidney parameters elevate.
Bone marrow suppression can also occur on cisplatin. Monitoring tests are
also regularly performed to assess the counts of different blood cells.
Cisplatin can interfere with normal hearing by affecting the cochleovestibular
nerve that controls hearing. (Cisplatin is what is called an ototoxic drug.)
In humans, a cisplatin-associated neuropathy has been described (involving
a sensory nerve interference). This has not been documented in the dog but
several cases of dogs who developed nerve problems (lower motor neuron weakness)
in their rear legs have been reported. It is not clear if this weakness,
though, was part of their cancer syndrome or due to the medication.
CONCERNS AND CAUTIONS
Cisplatin concentrates in the liver, intestines and kidneys and is still
present in the body 6 months after treatment but 80% eliminated in urine
after 48 hours.
Cats are vulnerable to severe pulmonary (lung) side effects and cannot
receive cisplatin.
Cisplatin cannot be used in patients with renal disease or bone marrow
suppression. Patients with renal disease can take another medication called
carboplatin.
Cisplatin impairs fertility and causes birth defects.
Copyright 2002 - 2008 by the Veterinary Information
Network, Inc. All rights reserved.
This work was originally published
by Veterinary Information
Network, Inc. (VIN) and is republished with VIN's permission
Chlorambucil (Leukeran¨)
is an oral alkylating agent which is very well tolerated. Mild decreases
in appetite and white blood cell/platelet counts can occur.
Brand Name: Leukeran®
Available in 2 mg tablets
Background
The treatment of cancer with medication (as opposed to surgery or radiation)
is especially helpful when the cancer in question is not localized to one
body area. Using medication allows the body's blood vessels to carry the
medication to even remote or otherwise inaccessible areas. This form of treatment
is called chemotherapy.
In order for chemotherapy to be effective, the medications must destroy
tumor cells and spare the normal body cells that may be adjacent. This is
accomplished by using medications that affect cell activities that go on predominant
in cancer cells but not in normal cells. Most chemotherapy agents focus on
the rapid cell division that characterizes the spread of cancer cells.
Chlorambucil is what is called an alkylating agent of the nitrogen mustard
group. Alkylating agents work by binding DNA strands so that the double
helix cannot unzip and replicate. (In other words, cell division is not
possible). They also bind other important biochemicals impairing their function
and can even break DNA strands. Cancer cells (and other cells that rapidly
divide) cannot reproduce. Lymphocytes, whose normal function involves antibody
production and other immune activities, are also very sensitive to the effects
of alkylating agents, thus making the alkylating agents helpful in treating
immune-mediated diseases (i.e., disease where the immune system erroneously
attacks the body).
Alkylating agents as a group have had problems with side effects. Because
chlorambucil is relatively slow acting, fewer side effects have been an
issue with this medication, especially in feline use. The use of chlorambucil
has made the treatment of numerous cancers and immune-mediated diseases
more successful especially in cats.
How This Medication Is Used
Chemotherapy protocols for the following cancers have included chlorambucil:
Lymphocytic leukemia
Multiple myeloma
Ovarian cancer
Lymphoma
Polycythemia rubra vera
Immune mediated conditions where chlorambucil may be especially helpful
include:
The pemphigus diseases
Eosinophilic granuloma complex
Inflammatory bowel disease
Feline infectious peritonitis
Immune-mediated hemolytic anemia
Immune-mediated platelet destruction
Chlorambucil is typically given daily or every other day.
Side Effects
The main side effect of concern with chlorambucil is bone marrow suppression.
The bone marrow is one's source of all blood cells, both white cells and
red cells. When the bone marrow is suppressed, one can develop an anemia
(inadequate amount of red blood cells), a drop in white cells (which constitute
the bulk of the immune system), or both. This side effect is generally evident
at some point during the second week of therapy and blood testing at this
time is definitely in order to determine if this side effect is occurring.
Once the medication is discontinued, the marrow should recover in another
1 to 2 weeks, though more severe and long lasting suppression has rarely
occurred.
Poodles and Kerry Blue terriers may have hair loss problems on chlorambucil
but the hair loss humans experience with chemotherapy generally does not
occur with dogs and cats.
Overdose of chlorambucil results in bone marrow suppression in all cell
lines as well as seizing.
Interactions With Other Drugs
The bone marrow suppression side effect of chlorambucil may be compounded
if chlorambucil is used with other medications that also share possible
bone marrow suppression as a side effect. Such medications include:
Chloramphenicol
Azathioprine
Colchicine
Cyclophosphamide
The use of chlorambucil may lead to the need to increase the dose of allopurinol
for patients who take it (such as uric acid bladder stones forming in Dalmatians).
Concerns and Cautions
The DNA poisoning effects of this medication precludes its use in pregnant
patients; furthermore, pregnant women should not handle this medication,
nor the urine or feces of animals taking chlorambucil.
Chlorambucil should not be used in patients with pre-existing bone marrow
suppression.
Chlorambucil is suppressive to the immune system and should be used with
caution in patients already immune suppressed (such as FIV+ cats) or with
chronic infections.
Chlorambucil may cause permanent infertility when given to patients prior
to puberty.
It is our policy not to give dosing information over the Internet.
By Wendy C. Brooks, DVM, DipABVP Educational Director,
VeterinaryPartner.com
Copyright 2002 - 2008 by the Veterinary Information Network, Inc. All rights
reserved.
This work was originally published by Veterinary
Information
Network, Inc. (VIN) and is republished with VIN's permission
***********************
The above information is simply informational.
It's intent is not to replace the advice of a veterinarian nor to assist
you in making a diagnosis of your pet. Please consult with your own veterinarian
for confirmation of any diagnosis. Your pets life may depend on it.
