Introduction to Chemotherapy for Osteosarcoma

 

The term "chemotherapy" describes a group of medications used in the treatment of cancer. It is usually given intravenously but certain medications can be given by mouth. The medications travel in the body and seek out cancer cells to destroy them. These medications are best given by veterinarians and technicians with experience in handling and administration, as well as the potential side effects and monitoring that should be done. To find an oncologist in your area, ask your primary veterinarian, call the nearest veterinary teaching hospital in your area, or contact www.acvim.org or www.vetcancersociety.org.

Many people are afraid of giving chemotherapy to their pets because of the potential for side effects. There are effective medications that can minimize the most common side effects. In addition, the doses of chemotherapy given to our dogs for the management of bone cancer are not high enough to cause severe toxicity.

In the treatment of bone cancer, chemotherapy is usually prescribed in addition to other treatments, namely amputation surgery. The traditional approach is to perform amputation surgery first, then follow up with the chemotherapy. This approach has the highest survival rate of all treatment options for managing bone cancer, based on currently accepted statistics. Depending on the oncologist and the overall health of the dog, the chemotherapy may be administered immediately after surgery, or within two weeks of the surgery.

The purpose of giving the chemotherapy after the primary tumor has been removed is to catch any stray cancer cells that may have already traveled through the blood to other areas. In bone cancer, the most common place for the cells to travel is the lungs. When cells travel, this is called "metastases". These metastatic deposits can be microscopic, not visible on xray. Since the medications also travel in the blood, they can find the metastatic cells and kill them.

The most commonly used chemotherapy medications used for management of bone cancer are cisplatin, carboplatin, and adriamycin. Some oncologists use a single agent in multiple doses several weeks apart, others suggest using combination therapy, rotating two drugs several weeks apart. The chemotherapy is given in "cycles" to provide the most exposure to different cancer cells as they are multiplying. Combination chemotherapy works in different ways and allows for cells to be destroyed at different stages in their cycle.

There is also another type of chemotherapy protocol, called the metronomic protocol. This protocol combines three medications: Piroxicam, deramaxx, Rimadyl (NSAID), doxycycline (an antibiotic) and cyclophosphamide, an oral chemotherapy drug. These three medications work on slowing down the blood supply to cancer cells, and also slow down their growth. The principle behind this is called "anti-angiogenesis" (angiogenesis means "creation of blood").

The metronomic protocol is usually used once the metastases are visible either on xray or exam, or in some cases where amputation is not an option. There are a lot of anectodal reports that support the use of these medications. The type of chemotherapy protocol for your dog should be discussed in detail with your oncologist. Most dogs handle chemotherapy very well. The most common side effects are nausea, vomiting, change in appetite and diarrhea. These side effects usually last for several days and can be minimized or avoided altogether with medications prescribed by your oncologist.

Most doctors will also advise not to feed your pet on the morning of the treatment. The chemotherapy sessions can last several hours or possibly all day. Blood work and urine tests are usually done before the chemotherapy is administered, and should be checked in between cycles as well. Occasionally the chemotherapy can affect the white blood cell count or liver/kidney functions, which is why monitoring is so important.

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CARBOPLATIN (Paraplatin)

 

CARBOPLATIN (Paraplatin) - Please discuss all information with your vet:

Platinum compounds, such as carboplatin, are some of the newest agents being used in cancer therapy. They have been used with success in many types of human cancer. Although the use of these agents in animals is relatively new, they have shown promise in a variety of tumors. Carboplatin is a clear agent that is painlessly administered directly into the vein over 15-20 minutes. The patient lies quietly on a padded table during administration and rarely needs any form of sedation.

Practically all anticancer drugs have side effects. However, their potential effect against the cancer 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 a 1% chance of fatality. Below are listed the potential side effects of carboplatin. Please consult your pet's doctor with any questions you may have about chemotherapy.

POTENTIAL SIDE EFFECTS OF CARBOPLATIN:

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 between 10 to 21 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. Therefore, prior to each carboplatin treatment, your pet will get a blood test called a Complete Blood Count (CBC). 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.

Stomach or Intestinal (Gastrointestinal) Discomfort. Many patients experience some form of stomach or intestinal discomfort two to seven days after a chemotherapy treatment. Your veterinarian will prescribe medication to try to prevent or treat the discomfort. Some veterinarians recommend giving the medication even if there are no overt signs of discomfort. Please discuss this with your vet.

Below are listed some steps you can take at home.

Upset stomach (Nausea)


1. If your pet begins to show any signs of upset stomach (drooling, "smacking" lips) or loss of appetite, administer the medicine your doctor prescribed for nausea.
2. Offer ice cubes every few hours.
3. After 12 hours, feed your pet small, frequent meals instead of one large meal.
4. Call your veterinarian at any time if you have concerns, or if the condition persists for more than 24 hours.

Vomiting


1. Do not give your pet any food or water for 12 hours.
2. After 12 hours, offer your pet ice cubes, then water, then small bland meals.
3. Call your veterinarian at any time if you have concerns, or if the condition persists for more than 24 hours.

Loss of Appetite


1. If your pet begins to show any signs of upset stomach or loss of appetite, administer the medicine your doctor prescribed for nausea.
2. Offer your pet four small meals a day.
3. Add warm broth, animal fats, and favorite foods to increase flavor and appeal.

Diarrhea


1. If your pet begins to show signs of diarrhea, administer the medicine your doctor prescribed for diarrhea.
2. Keep water available at all times.
3. If your pet is also not eating, offer chicken or beef broth.
4. Give Pepto Bismol (dogs only), 1 tablespoon per 10 lbs of body weight every 4 to 6 hours if okay with your veterinarian.
5. Call your veterinarian at any time if you have concerns, or if the condition persists for more than 24 hours.

Deafness

Although this problem has never been documented in animals, it is a rare problem in human patients and should be a side effect you are aware of.

Kidney Damage

Although kidney damage as a result of various platinum agents is not uncommon, kidney problems related to carboplatin are rare. However, your pet's kidney function should be assessed by performing certain blood and urine tests prior to each treatment. If any abnormalities are detected, intravenous or subcutaneous fluids may be necessary to correct the problem and the chemotherapy may not be administered until the tests return to normal.

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 carboplatin, it would develop upon administration, and your veterinarian and the hospital staff are trained to treat patients for allergic reaction.

Hair Loss (Alopecia)

Pets who receive carboplatin 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. Cats may, however, lose all or most of their whiskers. Please ask your pet's doctor about the possibility of hair loss in your pet.

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ADRIAMYCIN (doxorubicin)

 

ADRIAMYCIN (doxorubicin) Please discuss all information with your vet

Adriamycin (doxorubicin) is a broad spectrum chemotherapy drug used to fight many forms of cancer and has been used for decades. 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.

The dose is calculated by a measurement called Body Surface Area, which your veterinarian can calculate based on your dog's weight. Baseline complete blood count should be done before the first administration of adriamycin. You should also check with your vet about testing for kidney function and liver function. Your vet may also prescribe medicine to administer for nausea, vomiting or diarrhea which can occur (see below).

Please note: One of the major side effects of adriamycin is the potential to affect heart function. When it occurs, it usually develops after several doses. Breeds that are prone to having underlying heart conditions, dogs with a large heart on xray and dogs with a previous history of heartworm infection should have baseline EKG (heart rhythm tracing) and possibly echocardiograms (heart ultrasound) before receiving adriamycin. This is not mandatory for every dog but needs to be discussed with your veterinarian and oncologist.

Other side effects:

Hair loss: 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 though out 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. Cats may, however, lose all or most of their whiskers. Please ask your pet's doctor about the possibility of hair loss in your pet.

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. Therefore, prior to each chemotherapy treatment, your pet should have a blood test performed called a complete blood count (CBC). 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.

Stomach or Intestinal (Gastrointestinal) Discomfort: Many patients experience some form of stomach or intestinal discomfort two or seven days after a chemotherapy treatment. Your veterinarian will prescribe medication to try to prevent or treat the discomfort. Below are listed some steps you can take at home.

Upset stomach (Nausea)


1. If your pet begins to show any signs of upset stomach (drooling, "smacking" lips) or loss of appetite, administer the medicine your doctor prescribed for nausea.
2. Offer ice cubes every few hours.
3. After 12 hours, feed your pet small, frequent meals instead of one large meal.
4. Call your veterinarian if you have concerns, or if the condition persists for more than 24 hours.

Vomiting


1. Do not give your pet any food or water for 12 hours.
2. After 12 hours, offer your pet ice cubes, then water, then small bland meals.
3. Call your veterinarian if you have concerns, or if the condition persists for more than 24 hours.

Loss of Appetite


1. If your pet begins to show any signs of upset stomach or loss of appetite, administer the medicine your doctor prescribed for nausea.
2. Offer your pet four small meals a day.
3. Add warm broth, animal fats, and favorite foods to increase flavor and appeal.

Diarrhea


1. If your pet begins to show signs of diarrhea, administer the medicine your doctor prescribed for diarrhea.
2. Keep water available at all times.
3. If your pet is also not eating, offer chicken or beef broth.
4. Ask your veterinarian about giving Pepto Bismol (dogs only), 1 tablespoon per 10 lbs of body weight every 4 to 6 hours.
5. Call your veterinarian if you have concerns, or if the condition persists for more than 24 hours.

Tissue damage: If Adriamycin is accidentally given outside the vein, severe tissue reactions can result, leading to tissue destruction. Therefore, Adriamycin is handled with the utmost care, and should only be administered by highly trained professionals. Secure intravenous access is paramount. If irritation of the injection site develops in the form of pain, swelling or redness, apply ice packs for 15 minutes every three hours. Call your veterinarian as soon as possible, 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 veterinarian and the hospital staff are 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 patients develop heart disease as a result of Adriamycin chemotherapy. Your veterinarian will discontinue the use of Adrimycin if heart disease is detected at any time.

Find out from your oncologist what can be done to minimize the risk of heart toxicity. Ask about the use of Co Enzyme Q-10 to protect against heart disease from adriamycin. There is also a medication called Zinecard (dexrazoxane) which is used in humans to prevent toxicity from adriamycin. Ask your oncologist if your dog is a candidate for this medication if available.

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CYCLOPHOSPHAMIDE (Cytoxan)

 

CYCLOPHOSPHAMIDE (Cytoxan) Please discuss all information with your vet

Cyclophosphamide is a chemotherapy drug used for a variety of cancer treatments. With regard to bone cancer, it is used as part of the Metronomic Protocol. In this setting, it is given as an oral medication, administered on a varied schedule according to different protocols, ranging from once a day to once a week. It functions both as an anti-cancer drug and as an immunosuppressant, which can cause significant side effects.

Practically all anticancer drugs have side effects. However, their potential effect against the cancer outweighs the possible side effects. Although serious adverse effects can occur with any chemotherapy, there is less than a 5% chance that your dog will be hospitalized with side effects and less than a 1% chance of fatality. Below are listed the potential side effects of cyclophoshamide. Please consult your veterinarian with any questions you may have about chemotherapy.

No specific precautions are needed when handling intact tablets. However, direct contact with crushed tablets, oral elixir or the dog's urine or stool should be avoided.

POTENTIAL SIDE EFFECTS OF CYCLOPHOSPHAMIDE:

Hemorrhagic Cystitis. The most important side effect of cyclophosphamide is hemorrhagic cystitis, which means "bloody urine". This is caused by the breakdown products of the drug. The longer the breakdown products are in contact with the bladder, the higher the likelihood of this side effect. For this reason, the following guidelines should be followed:

  • The medication should be given as a single dose in the morning.
  • Your dog should be encouraged to drink plenty of fluids (increasing fluid intake).
  • Your dog should be encouraged to urinate frequently during the day, which may mean more frequent potty breaks than usual.
  • The veterinarian may prescribe a "water pill" (diuretic) to be given on the days that the cyclophosphamide is given. This will dramatically decrease the risk of hemorrhagic cystitis, because it will increase the volume of urine and trigger your dog to drink more fluids.
  • Safe handling procedures recommend the use of gloves when administering any chemo agent.
The easiest way to check if your dog has hemorrhagic cystitis is to inspect the urine. This can be done several times a week, by holding an aluminum pie plate under him/her while urinating. If the urine appears bloody or dark, do not give any further doses of cyclophoshamide and contact your veterinarian immediately. If the urine appears normal, check with your veterinarian periodically for a urinalysis test which can show small amounts of blood in the urine not visible to the naked eye. It is also important to check for urine infections, which can also cause blood in the urine.

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 between 10 to 21 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. Therefore, your pet should have a blood test called a Complete Blood Count (CBC). If there is 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.

Less commonly, cyclophosphamide can affect the platelets and the red blood cells. These cells can also be monitored by the Complete Blood Count (CBC).

Stomach or Intestinal (Gastrointestinal) Discomfort. Some patients experience some form of stomach or intestinal discomfort while on a chemotherapy drug. The most common side effects are upset stomach (nausea) which can cause a change in appetite, vomiting or diarrhea. Your veterinarian may prescribe medication to try to prevent or treat the discomfort. Some veterinarians recommend giving the medication even if there are no overt signs of discomfort. Please discuss this with your vet. Below are listed some steps you can take at home.

Upset stomach (Nausea)


1. If your pet begins to show any signs of upset stomach (drooling, "smacking" lips) or loss of appetite, administer the medicine your doctor prescribed for nausea.
2. Offer ice cubes every few hours.
3. After 12 hours, feed your pet small, frequent meals instead of one large meal.
4. Call your veterinarian at any time if you have concerns, or if the condition persists for more than 24 hours.

Vomiting


1. Do not give your pet any food or water for 12 hours.
2. After 12 hours, offer your pet ice cubes, then water, then small bland meals.
3. Call your veterinarian at any time if you have concerns, or if the condition persists for more than 24 hours.

Loss of Appetite


1. If your pet begins to show any signs of upset stomach or loss of appetite, administer the medicine your doctor prescribed for nausea.
2. Offer your pet four small meals a day.
3. Add warm broth, animal fats, and favorite foods to increase flavor and appeal.

Diarrhea


1. If your pet begins to show signs of diarrhea, administer the medicine your doctor prescribed for diarrhea.
2. Keep water available at all times.
3. If your pet is also not eating, offer chicken or beef broth.
4. Give Pepto Bismol (dogs only), 1 tablespoon per 10 lbs of body weight every 4 to 6 hours if okay with your veterinarian.
5. Contact your veterinarian IMMEDIATELY if you notice any blood in the diarrhea.
6. Call your veterinarian at any time if you have concerns, or if the condition persists for more than 24 hours.

Kidney damage can result from chemotherapy drugs. Your dog's kidney function should be checked by performing kidney function blood tests and urine tests prior to each treatment. If any abnormalities are detected, intravenous or subcutaneous fluids may be necessary to correct the problem and the cyclophoshamide may not be prescribed until the tests return to normal.

Allergic Reactions to chemotherapeutic agents is rare, and not a problem you will have to treat at home. Should your pet have an allergic reaction to cyclophosphamide contact your veterinarian immediately.

Hair Loss (Alopecia) Pets who receive cyclophoshamide 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 veterinarian about the possibility of hair loss.

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Cisplatin (Platinol)

 

Cisplatin is not commonly used anymore due to its potential toxicity, and is often replaced with Carboplatin.

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