I have a paraneoplastic neurological syndrome. What is that? It is a process whereby the body’s immune system starts fighting the central nervous system in response to having had cancer, having cancer or having a developing cancer. It is a rare disorder and most doctors simply have no idea what it is or how to treat it. The other bad thing is that it can manifest itself in so many ways. For example, I have been diagnosed with transverse myelitis and progressive polyneuropathies in addition to suffering symptoms like myoclonus, chronic pain and chronic fatigue. I have some antibodies that shouldn’t be there normally. However, my cancer is gone – at least from the standpoint of the detection systems currently available to medicine. But, I am sick with progressive neurological symptoms that have made me wheelchair bound.
My treatment started with high dose steroids followed by high dose IVIG (combined with steroids and anti-nausea medication to help with the side effects of the IVIG). While this treatment likely slowed my disease down, it did not stop it. After visiting the Mayo Clinic in 2011, it was suggested that I be put on a course of either IV or oral cyclophosphamide.
***We started with monthly IV treatments. However, it made me so sick; I only had two or three good days out of a month. The rest of the time was lost in a fog of nausea and dizziness.***
So, we switched to the oral medicine. The initial dose was 50 mg twice per day. After taking this dose for several months, my blood testing showed a significant drop in white cells and platelets as well as a mild anemia. So, the dosage was changed first to 25 mg three times per day and finally to 25 mg twice per day. I have been taking it now for more than two years.
***For about 18 months, my disease was stable. While I did not get back what had been lost, new or more serious symptoms seemed to have subsided.***
But in the middle of 2013, the disease began to progress once more with new and more severe symptoms. But, as a fighter, I am not giving up and try to keep myself in a routine and doing as much as I possibly can every day.
Let me tell you a little bit about cyclophosphamide. Cyclophosphamide, also called Cytoxan, is classified as a “cytotoxic agent”, because it has a toxic effect on many types of cells (“good” cells as well as “bad”). Cyclophosphamide is one of a number of medications first developed as a chemotherapy drug (a medication used in the treatment of cancer).
***And a bit of trivia, Cytoxan is a derivative of mustard gas. Yes, you read it correctly, mustard gas – that stuff that killed or seriously disabled so many soldiers in World War I.***
It was discovered that – in addition to its usefulness in cancer – cyclophosphamide also has a significant ability to suppress the immune system. Thus, the medicine is very effective in the treatment of immunologically–mediated diseases, including many paraneoplastic syndromes.
***In general, much lower doses of cyclophosphamide are used to treat autoimmune diseases than are used to treat cancer. However, the doses of cyclophosphamide used are still high enough to cause a significant number of side-effects, and the drug must be used with great caution.***
As mentioned, the drug has a big impact on the blood cells – white cells, red cells and platelets. The bone marrow is the organ of the body that makes red blood cells (which carry oxygen), white blood cells (which fight infection), and platelets (which help the blood clot). Nearly all patients treated with cyclophosphamide experience some suppression of the bone marrow’s ability to produce these vital blood elements. Thus, careful monitoring of blood counts is essential during cyclophosphamide therapy. Suppression of the bone marrow by cyclophosphamide is usually transient – which means that it is responsive to a decrease in dose or discontinuation of the medicine – but dangerously low levels of any of these three cell lines (or even permanent bone marrow failure) may occur.
***The white blood cells are the cell line that is usually most sensitive to the effects of cyclophosphamide. When cyclophosphamide is given intravenously, the white blood cell count tends to reach its low point (“nadir”) between 7 and 14 days after administration. Therefore, blood cell counts should be measured approximately 10 days after the administration of cyclophosphamide, and repeated as often as needed to insure that the counts do not go too low. This normally means checking blood counts every 2 – 4 weeks.
When cyclophosphamide is given orally (every day, rather than once a month), blood counts should be checked about 7 days after starting treatment and then no less frequently than once every 3 to 4 weeks.***
After reading through the many possible side effects, a reasonable person might conclude that the treatment appears worse than the disease it is intended to treat! Following is the first few sentences from the product information insert provided by my pharmacy with my prescription:
“SIDE EFFECTS: Nausea, vomiting, loss of appetite, stomach ache, diarrhea, or darkening of the skin/nails may occur. Nausea can be severe. In some cases, drug therapy may be necessary to prevent or relieve nausea and vomiting. . .”
However, for people in my spot, whose disease has not completely responded to the combination of steroids and IVIG, cyclophosphamide may be a life–saving medicine.
The tablets don’t look so menacing but it really takes you back a little bit when the nurse who administers them in the hospital wears thick rubber gloves. At home, I just pop them in the mouth like my other medications.
***Cyclophosphamide increases the risk of “opportunistic” infections, i.e. infections that a person’s intact immune system would normally be able to fight off.***
Thus, cyclophosphamide does not enhance a patient’s susceptibility to the common cold; it does heighten the risk of more serious infections, including tuberculosis, fungal infections, and serious viral infections. Several specific infections frequently associated with cyclophosphamide uses (or the use of immunosuppressive drugs in general) are described below:
“Thrush” — Thrush is a fungal infection of the mouth caused by Candida. It generally appears as white spots on the inside of the mouth, and is easily treatable with the use of anti–fungal mouthwash or troches. Sometimes Candida infections also involve the esophagus (the “food tube” leading from the mouth to the stomach). This condition, called “Candida esophagitis”, often results in pain on swallowing, and must be treated with potent anti–fungal medications such as fluconazole.
“Shingles” — or Herpes zoster. “Shingles” results from reactivation of the virus that causes chickenpox (Varicella zoster). Nearly everyone who is older than 5 had chickenpox at one time, generally as a child. Normally, even after the rash and other symptoms of chickenpox subside, the virus that caused the sickness continues to reside in the body in a “dormant” state, hiding in the root of one of the nerves along the spine. Decades later, as the immune system wanes slightly with age (a normal part of the aging process) or when the immune system is suppressed (by medications such as cyclophosphamide), the virus become active again. When it reactivates, Varicella zoster usually causes a painful rash in the distribution of a single nerve, such as over one side of the face or down one arm. The rash is characterized by groups of small vesicles (blisters) sitting on a base of reddened skin, and may be extremely painful. “Shingles” is treatable with anti–viral medicines. These should be instituted as soon as possible. Narcotic pain medicines may also be necessary for several weeks. In a small minority of cases, “shingles” results in pain that can last for months. This condition is called “post–herpetic neuralgia”.
Pneumocystis carinii pneumonia (“PCP”) — Pneumocystis carinii is a fungus that resides within the lungs of most people. People with intact immune systems have no trouble keeping the organism at bay. In patients who are immune-suppressed, the organism can cause a serious type of pneumonia: PCP.
***Many of the side effects of cyclophosphamide are most likely to occur while taking the medication. With those side effects, the risk of their occurrence diminishes greatly after discontinuation of the drug.***
In contrast, the risk of cancer associated with cyclophosphamide use may continue for many years, even after patients stop the medication.
***The risk of cancer appears to be dependent upon the length of time patients have taken the medication and the cumulative dosage of the drug.***
Patients who have taken cyclophosphamide have an increased risk for at least two primary types of malignancy: leukemia/lymphoma and bladder cancer. There may also be increased risks for other kinds of cancer, but the risks are less high.
Leukemia/lymphoma — One of the long term side effects of cyclophosphamide use is a significant increase in the risk of bone marrow and lymph node cancers (known as leukemia and lymphoma, respectively). Physicians are currently unable to predict which patients will be at risk for these complications. The best means of avoiding these types of cancer is to use cyclophosphamide judiciously: the lowest possible dose of the medicine for the shortest length of time necessary to control the disease.
Bladder cancer — Cyclophosphamide has a tendency to damage the bladder. This damage predisposes patients to the development of bladder cancer. The risk of bladder cancer (and of other bladder complications) is greater when cyclophosphamide is administered in the oral daily form. Among patients followed for up to 15 years, the projected incidence of bladder cancer was as high as 16%. Therefore, patients who have been treated with cyclophosphamide need to be followed indefinitely for the possibility of bladder complications of the treatment. The best method of screening for this complication is to check for red blood cells in the urine by performing a urinalysis, followed by cystoscopy if red blood cells are present. Patients shown to have bladder damage by cyclophosphamide, i.e. to have drug-induced cystitis, should undergo surveillance cystoscopies at regular intervals as determined by their urologists.
When cyclophosphamide is administered intravenously, a bladder-protective medicine called MESNA may be given at the same time. MESNA appears to neutralize the toxic metabolite of cyclophosphamide (acrolein) that is thought to be responsible for the bladder complications.
Additional strategies for decreasing the bladder toxicity of cyclophosphamide include:
1) giving intravenous hydration prior to cyclophosphamide;
2) taking all of the medicine in a single morning dose and washing it down with a large amount of fluid; and
3) drinking ample quantities of fluid throughout the day (eight 8–ounce glasses of water) to maintain a brisk urine output.
***This is why I drink lots and lots of fluids every day and throughout the day. I want to keep any residual cyclophosphamide flushed out of the bladder as efficiently as possible.***
However, because I have a neurogenic bladder as a result of the paraneoplastic syndrome, all that fluid makes the management of my incontinence (sudden urges to go) and urine retention even that much more difficult to manage.
In addition to cancer, cyclophosphamide may cause a variable amount of bleeding from the bladder, a complication known as “hemorrhagic cystitis”. This bleeding may range from a few red blood cells in the urine (invisible to the naked eye; only detectable by examining the urine under the microscope) to life–threatening hemorrhage from the bladder. If any bleeding from the bladder is discovered while a patient is taking cyclophosphamide, the medicine should be stopped until the bladder can be evaluated by cystoscopy.
And finally, cyclophosphamide may cause infertility in both men and women who are treated with the medication. As with many of cyclophosphamide’s side effects, the risk of infertility appears to be related to the length of time a patient receives the drug (and probably the cumulative dose, as well). A woman’s age may also affect her risk of infertility, with the occurrence of early menopause higher in women over the age of 30 at the time treatment is begun.
And may I repeat, despite all of these dangerous side effects, taking this drug has likely made it possible for me to have remained relatively stable from 2011 to 2013 before a decline began in the late summer of 2013. I continue to take the drug and will do so until my follow-up appointment at the Mayo Clinic in June 2014. Since mid-2013, I have had bradycardia (a very slow heart rate) caused by a cardiac neuropathy, several incidents of syncope (passing out), variable blood pressure, increased fatigue, and increasing pain in the muscles and tendons with weakness now on both sides of my body.
But, I will never, ever give up! Keep fighting!!
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