Bcg treatments side effects

Contents

Theracys

SIDE EFFECTS

The most common adverse reactions observed with TheraCys treatment at a rate > 10% were transient dysuria, urinary frequency and urgency, malaise, hematuria, fever, chills, cystitis, and mild nausea.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a medicinal product cannot be directly compared to rates in the clinical trials of another medicinal product and may not reflect the rates observed in practice.

Administration of TheraCys causes an inflammatory response in the bladder, thus requiring careful patient monitoring. Symptoms of bladder irritability are reported in approximately 50% of patients receiving TheraCys and typically begin 4-6 hours after instillation and last 24-72 hours. The irritative reactions usually are seen following the third instillation and tend to increase in severity after each administration. There is no evidence that dose reduction or antituberculous drug therapy can prevent or lessen the irritative symptoms of TheraCys.

In a clinical trial conducted in the United States, patients with stage Ta or T1 papillary tumor with 2 or more recurrences within the last 12 months, with carcinoma in situ (CIS), or with both of these conditions, were randomized to receive treatment with intravesical TheraCys or doxorubicin. Prior therapy with either BCG or doxorubicin was not allowed. Patients with muscle-invasive cancers or incomplete resection of papillary tumors were not eligible. Onehundred and twelve patients received TheraCys in 6 weekly instillations, followed by single instillations at 3, 6, 12, 18, and 24 months after enrollment, and were included in safety analyses. In the control group, 119 patients received doxorubicin in 5 weekly treatments, followed by 11 monthly treatments. Safety information was collected prior to each treatment dose.

Table 1 shows the frequency of adverse reactions observed in this trial. Local irritative symptoms were more common with TheraCys than with doxorubicin; however, grade ≥ 3 irritative toxicity was similar, occurring in approximately 2-7% of patients. Systemic symptoms (fever, chills, malaise, anorexia) were also more common with TheraCys. Overall, grade ≥ 3 toxicities were seen in 26 patients (23%) treated with TheraCys and 25 patients (21%) treated with doxorubicin. TheraCys treatment was discontinued in twelve patients due to toxicity.

Table 1: Adverse Reactions Reported in Patients Treated with TheraCys in a Trial Conducted in the United States

System/Organ Class Adverse reaction Study Arm
TheraCys
(N=112)
Doxorubicin
(N=119)
All Grades % Grade ≥ 3 % All Grades % Grade ≥ 3 %
Infections and Infestations
Cystitis 29.5 0 19.3 0.8
Urinary tract infection 17.9 0 17.6 0
Pulmonary infection 2.7 0 4.2 0.8
Systemic infection 2.7 1.8 0.8 0
Infection 0.9 0.9 0.8 0
Blood and Lymphatic System Disorders
Anemia 20.5 0 24.4 0
Leukopenia 5.4 0 5.9 0
Coagulopathy/ Thrombocytopenia 0.9 0 0.8 0
Metabolism and Nutrition Disorders
Anorexia 10.7 0 5.0 0
Nervous System Disorders
Headache 1.8 0 3.4 0
Dizziness 0.9 0 0.8 0
Cardiac Disorders
Cardiac (unclassified) 2.7 0 3.4 0.8
Gastrointestinal Disorders
Nausea/Vomiting 16.1 0 8.4 0.8
Diarrhea 6.3 0 1.7 0
Abdominal pain 2.7 0 2.5 0
Constipation 0.9 0 0.8 0
Hepatobiliary Disorders
Liver involvement 2.7 0 0.8 0
Skin and Subcutaneous Tissue Disorders
Skin rash 1.8 0 2.5 0
Musculoskeletal, Connective Tissue, and Bone Disorders
Arthralgia/Myalgia/ Arthritis 7.1 0.9 4.2 0
Flank pain 0.9 0 0.8 0
Renal and Urinary Disorders
Dysuria 51.8 3.6 40.3 5.9
Urinary frequency 40.2 1.8 28.6 4.2
Hematuria 39.3 7.1 27.7 6.7
Urinary urgency 17.9 0.9 11.8 2.5
Renal toxicity (NOS) 9.8 1.8 9.2 0.8
Urinary incontinence 6.3 0 0.8 0.8
Bladder cramps/pain 6.3 0 5.0 1.7
Contracted bladder 5.4 0.9 5.0 0.8
Tissue in urine 0.9 0 1.7 0
Ureteral obstruction 0.9 0.9 0 0
Reproductive System and Breast Disorders
Genital pain 9.8 0 13.4 1.7
General Disorders and Administration Site Conditions
Malaise 40.2 1.8 14.3 0
Fever ( > 38°C) 38.4 2.7 9.2 0
Chills 33.9 2.7 5.9 0
Fatigue 0.9 0 0 0

Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of TheraCys. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Infections and Infestations

BCG Infection: BCG is capable of dissemination when administered by the intravesical route. Serious infections, including sepsis with associated mortality, have been reported. BCG infections have also been reported in eye, lung, liver, bone, bone marrow, kidney, regional lymph nodes, peritoneum, genitourinary tract (orchitis/epididymitis), and prostate (e.g., Granulomatous prostatitis). BCG infection of aneurysms and prosthetic devices (including arterial grafts, cardiac devices and artificial joints) has also been reported.

Joint symptoms (arthritis, arthralgia), ocular symptoms (including conjunctivitis, uveitis, iritis, keratitis, granulomatous choreoretinitis), urinary symptoms (including urethritis), skin rash, alone or in combination (Reiter’s syndrome), have been reported following administration of TheraCys. For the reports of Reiter’s syndrome, the risk seems to be more elevated among patients who are positive for HLA-B27.

Renal abscess

Respiratory, Thoracic and Mediastinal Disorders

Pneumonia, interstitial lung disease

Skin and Subcutaneous Tissue Disorders

Erythema nodosum

Renal and Urinary Disorders

Renal failure, pyelonephritis, nephritis (including tubulointerstitial nephritis, interstitial nephritis and glomerulonephritis)

Urinary retention (including bladder tamponade and feeling of residual urine)

General Disorders and Administration Site Conditions

Flu-like symptoms

Investigations (Laboratory Tests)

Abnormal/increased blood creatinine or blood urea nitrogen (BUN)

Read the entire FDA prescribing information for Theracys (BCG Live (Intravesical))

Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

Abstract

Intravesical Bacilli Calmette-Guérin (BCG) immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain) immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin), he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS) prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP) Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin) and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment.

1. Introduction

The term superficial bladder cancer refers to Ta, T1, and T carcinoma in situ (cis) lesions of any grade. Tumor grade and stage clearly have a strong influence on tumour progression and recurrence. The principal technique for the diagnosis and treatment of the superficial bladder lesions is endoscopy. Adjunctive intravesical therapy is available for residual disease or for tumour prophylaxis.

Since Morales et al. (1992) found an immunologically responsive tumour system, Bacillus Calmette-Guérin (BCG) has established itself as the most successful intravesical agent for the treatment and prophylaxis of different forms of superficial bladder cancer. The exact mechanism of BGC is still unknown. The bacilli attach to tumor cells through a novel fibronectin protein . Following attachment, the BCG is internalized into the tumour cell . Raised levels of Interleukin-12 result in T helper (Th1) activation and increased interferon-γ production results in a positive ratio of CD4 helper and CD8 cytolytic T cells . Furthermore, it has been suggested that intravesical BCG increases nitric oxide levels, which has been shown to inhibit tumour growth .

2. Case Report

We present the case of an 82-year-old man with a background of lung adenocarcinoma diagnosed in 1996 and treated with a left upper lobe lobectomy. Further he had Extrinsic Allergic Alveolitis (EAA) diagnosed in 2006. He also had multiple Squamous Cell Carcinoma lesions of the forearm, forehead and chest, as well as macular degeneration. Bladder Transitional Cell Carcinoma (TCC) was diagnosed in Zimbabwe in May 2009 with a histology of G2 pTa and was resected endoscopically. Surveillance flexible cystoscopies were unremarkable until 2011 when a positive bladder biopsy proved T carcinoma in situ (cis). BCG (TICE strain) induction therapy was initiated. The patient received one installation per week. The patient required a tetanus vaccination due to an unrelated incident, which indicated temporary suspension of treatment after the fourth installation. However during the first four installations, he suffered no side effects and the procedure was well tolerated. After a six-week pause, the BCG induction therapy continued with two further instillations.

Two weeks after the last BCG instillation, the patient was admitted with lethargy, loss of appetite, fever, and rigors. He had no respiratory or urinary symptoms. On examination, he was pyrexial (38.6°C), clinically dehydrated, hypotensive (85/34 mmHg), tachycardic (95/minute), and capillary refill was four seconds. ECG showed sinus rhythm. The cardiovascular and respiratory examinations were normal and the patient was saturating 96% oxygen on room air. Admission blood tests were unremarkable except for a mildly raised C-Reactive Protein (85 mg/L). Urine dipstick showed one plus of leukocyte and three plus of blood and ketones. A midstream urine culture and blood cultures were taken for aerobic bacteria, anaerobic bacteria, and tuberculosis (TB). Further samples were obtained for Influenza Polymerase Chain Reaction (PCR). Ultrasound of the urinary tract was normal. The chest X-ray (CXR) was unremarkable (Figure 1). Intravenous tazocin and gentamicin and fluids were started for suspected urological sepsis.


Figure 1
Chest X-ray on day one of admission.

Despite treatment, the patient suffered intermittent and worsening fever and developed type two respiratory failure prompting admission to the Intensive Care Unit (ITU) on day two of admission. A central venous catheter and arterial line were inserted, and Bilevel Positive Airway Pressure (BiPAP) was initiated. The CXR indicated that the type two respiratory failure was secondary to worsening Acute Respiratory Distress Syndrome (Figure 2). Respiratory physicians started antituberculosis triple therapy (ethambutol, isoniazid, and rifampicin) and prednisolone for suspected BGC-osis. Negative blood cultures and a strong clinical suspicion of BCG-osis prompted microbiology to advise discontinuation of tazocin and gentamicin.


Figure 2
Chest X-ray on day two of admission.

Overall, the patient spent six days on ITU. He required progressively lower ventilation pressures and was thus transferred to the respiratory ward. On the seventh day of anti-TB therapy, the patient showed deranged liver function tests and therefore isoniazid and rifampicin were discontinued. His liver function tests, normalized within two days of stopping these hepatotoxic agents. The patient required a forty-two-day hospital stay since he was significantly below his normal baseline function. The patient was discharged on long-term ethambutol and appropriate follow-up with the urology and respiratory teams. The manufacturer of the BCG product was notified of the adverse event.

3. Discussion

BCG is a live attenuated strain of Mycobacterium bovis. Thus there is potential for serious illness and death. Acid Fast Bacteria (AFB) have been demonstrated in the bladder 16.5 months after completion of intravesical installations .

Most patients only experience mild side effects. These include fever and lower urinary tract symptoms including dysuria, frequency, and urgency that last for several days and worsen during the course of treatment . Frank haematuria is also a common complication (40%) and it is a relative contraindication for BCG delivery.

BCG-osis occurs following systemic absorption of BCG into the bloodstream. Risk factors include traumatic catheterization and a recent bladder tumour resection, where the integrity of the bladder mucosa is disturbed . A fever exceeding 38.5°C lasting over 24 hours despite antipyretic therapy, or a recorded fever higher than 39.5°C, should prompt a high clinical suspicion of BCG-osis and should be treated empirically with Isoniazid (300 mg od) for three months . It is generally more severe in patients who suffer from preexisting lung or liver disease. BCG sepsis is very rare , requiring resuscitation, ventilatory support, intensive care input, and triple anti-TB therapy.

Infection with TB following intravesical BCG treatment has been categorized into “early” and “late” syndromes, presenting within or after three months, respectively . The late presentations, such as in this case, are thought to result from “reactivation of infection after successful immunologic control of early dissemination” . Infection has been reported as late as three years after the cessation of intra-vesical BCG treatment .

This case report indicates that although intravesical BCG immunotherapy is safe and usually produces only mild side effects , the adverse reactions can be severe and unpredictable. Therefore we should remain vigilant at all stages of treatment.

Bacillus Calmette-Guerin (BCG, TICE®, TheraCys®)

How to Take Bacillus Calmette-Guerin

BCG is given directly into the bladder (called intravesicular) through a catheter. The medicine is left in the bladder for 1-2 hours. The dosage and schedule is determined by your healthcare provider. It is not uncommon to have urinary frequency (need to go often) or painful urination for 48 hours after treatment. If this continues after 48 hours, call your doctor or nurse.

How the Intravesicular Treatment is Given

  • You should limit your fluid intake starting the night prior to the procedure and have no fluids for 4 hours before. This is so you will be able to hold your urine in during the procedure for the full treatment time. In addition, the area receives more concentrated (and effective) doses of the medicine with less urine output during the procedure.
  • If you take a diuretic (water pill), you will be told to not take this for at least 4 hours before the procedure.
  • A urinary catheter is inserted into the bladder and any urine is drained.
  • The BCG is given through the catheter, into the bladder. The catheter may be removed or clamped and remain in place based on your provider’s recommendation.
  • You will need to hold the BCG in your bladder for 1-2 hours. You may need to change positions every 15 minutes to be sure the medicine reaches all areas of the bladder. Do this by rolling on your side, back, other side and stomach.

Precautions After Treatment

  • Try not to urinate for 1-2 hours after the procedure.
  • You should sit to urinate for 6 hours after the treatment to prevent splashing urine on the skin or exposing others to the medication.
  • Do not use public toilets or urinate outside.
  • For the first six hours after treatment, after each time you urinate:
    • Add 2 cups of household bleach to the toilet bowl and close the lid.
    • Wait 15-20 minutes and then flush the toilet with the lid down.
  • Wash your hands and genital area with soap and water after urinating to remove any traces of the medication from your skin and prevent skin irritation.
  • Drink plenty of fluids, starting after the first time you urinate and for 8-12 hours after your treatment to flush your bladder.
  • If you have urine incontinence, immediately wash your clothes in the washer. Do not wash with other clothes.
  • If using an incontinence pad, pour bleach on the pad, allow to soak in and place it in plastic bag and discard with trash.
  • Call your provider if you develop a fever (greater than 101.3° F/38.5°C) or shaking chills.

Medication Interactions

Immunosuppressants and/or bone marrow depressants and/or radiation interfere with the development of the immune response and should not be used in combination with BCG. Antimicrobial therapy for other infections may interfere with the effectiveness of TICE® BCG. Be sure to tell your healthcare provider about all medications and supplements you take.

Possible Side Effects of BCG

There are a number of things you can do to manage the side effects of BCG. Talk to your care team about these recommendations. They can help you decide what will work best for you. These are some of the most common or important side effects:

Bladder Irritability

This medication can cause irritation to the bladder, including difficulty or painful urination (dysuria), blood in the urine (hematuria), and increased urgency (strong feeling of need to urinate) or frequency of urination. Patients are advised to increase fluid intake after administration of this medication to “flush” the bladder. You should report any of the urinary symptoms listed above that last more that 48 hours to your healthcare team for further management instructions.

Fatigue

Fatigue  is very common during cancer treatment and is an overwhelming feeling of exhaustion that is not usually relieved by rest. While on cancer treatment, and for a period after, you may need to adjust your schedule to manage fatigue. Plan times to rest during the day and conserve energy for more important activities. Exercise can help combat fatigue; a simple daily walk with a friend can help. Talk to your healthcare team for helpful tips on dealing with this side effect.

Flu-like Symptoms

Your doctor or nurse can recommend medication and other strategies to relieve aches, pains and generalized malaise.

BCG Infection Reaction

This rare reaction to BCG can occur following exposure to BCG, when given within one week of a biopsy, TUR (trans-urethral resection) surgery, or traumatic bladder catheterization. Symptoms of a BCG reaction include unexplained high fever lasting 24-48 hours or more, chills, confusion, dizziness or lightheadedness (symptoms of low blood pressure), or shortness of breath. You should notify your doctor immediately if you experience any of these symptoms. BCG reaction can also cause pneumonitis (inflammation of the lungs), hepatitis, prostatitis (infection or inflammation of the prostate), epididymal-orchitis (inflammation of the testicles), respiratory distress and other symptoms of sepsis (widespread infection).

Reproductive Concerns

Men having this treatment can pass on BCG during sex. To protect your partner from coming into contact with BCG, you should not have sex for 48 hours after each treatment. Use a condom if you have sex at other times during the treatment course and for six weeks after treatment has ended.

This medication should not be given to a pregnant woman except when clearly needed. Women should be advised not to become pregnant while on therapy. Breastfeeding while receiving this medication is not recommended.

BCG treatment for bladder cancer

If you are having a course of BCG directly into your bladder (intravesical BCG), you have it in the hospital outpatient department. Your nurse or doctor will give you advice on preparing for your treatment. For example, they will ask you to limit the amount of fluids you drink 4 to 6 hours before BCG treatment. This can:

  • make it easier for you to keep the BCG in your bladder for the required time (stops you needing to pass urine (pee) too early)
  • increase the concentration of the BCG drug in your bladder.

People who take water tablets (diuretics) should take them after the treatment. Tell your doctor if you take any medications.

Before you have the BCG treatment, you are asked to lie down on a couch. A nurse passes a tube (catheter) through your urethra and into your bladder. The nurse then slowly puts the BCG directly into your bladder through the catheter.

During treatment

Once the drug is in your bladder, the nurse usually takes the catheter out. They ask you not to pass urine for 2 hours. This gives the BCG time to work.

You can get up and walk around while waiting for the treatment to finish. Your bladder may feel full and a bit uncomfortable. You can go to the toilet as soon as the treatment is finished.

Sometimes, the nurse leaves the catheter in and clamps it to keep the BCG in your bladder. When the treatment is over, the nurse removes the clamp and the BCG drains from your bladder into a urine bag. Your nurse can then take the catheter out.

After treatment

It is important to remember that BCG is a live vaccine and other people should not be exposed to it. The nurse will ask you to take certain precautions for 6 hours after treatment. This will protect you and others from coming into contact with the BCG.

You will be asked to:

  • sit down to pass urine – this avoids splashing urine on the toilet seat
  • wash the skin in and around your genital area with soap and water after you pass urine – this cleans any drops of BCG that may have splashed on to your skin
  • put undiluted bleach into the toilet bowl after you have passed urine and leave it for 15 minutes before flushing
  • wash your hands carefully after passing urine with soap and water.

For about 2 days after each treatment, you will usually be asked to drink at least 2 litres (3 ½ pints) of fluid a day. This helps to flush the drug out of your bladder.

Talk to your nurse if you are worried. They will tell you what you need to do after treatment.

Bacillus Calmette Guerin (BCG) Treatment for Non-Muscle Invasive Bladder Cancer: Risks / Benefits

What are potential side effects and complications of BCG treatment?

Benefits of this treatment outweigh risks and side effects.

Common side effects within 24 hours post procedure that do NOT need a phone call to the office include:

  • Small amount of blood in urine
  • Low grade fever (99-100°F)
  • Tiredness
  • Urinary frequency, urgency and burning with urination
  • Muscle or joint achiness

You will be given prescriptions to address the urinary symptoms if needed. You will be able to treat fever with over-the-counter pain/fever medication.

Other less common to rare side effects (some may require call to physician’s office):

  • Skin rash/ eruptions
  • Fever greater than 101.3°F
  • Nausea/vomiting/anorexia (lack appetite)
  • Urinary incontinence
  • Bladder spasms
  • Blood in urine with inability to pass urine due to clots
  • Urinary tract infection
  • Inflammation in testicle/scrotal region
  • Abscess formation
  • Ureteral obstruction
  • Bladder contracture/necrosis (cell death)
  • BCG sepsis
  • Neutropenia (low count of white blood cells that fight off infection)
  • Tissue necrosis with leakage of fluid
  • Pneumonitis
  • Hepatitis

Intravesical BCG is contraindicated (should not be used) with the following conditions:

  • Within 7 to 14 days of bladder or prostatic surgery, including biops
  • Within 7 to 14 days following traumatic catheterization
  • Traumatic catheterization or blood in urine day of treatment
  • Pregnant or nursing patients
  • Patients with active tuberculosis
  • Immunosuppressed patients with congenital or acquired immune deficiency. If treatment is still deemed necessary, informed consent must be discussed by prescribing provider and documented in patient’s record.
  • Symptomatic urinary tract infection: Severe burning on urination; foul-smelling urine; fever/chills; or if you have had urinary tract infection and experience similar symptoms
  • In the presence of illness with fever
  • Patients on treatment with certain antibiotics that may interfere with effectiveness of BCG (discuss with prescribing or collaborating provider before administration)
  • Any previous allergies or adverse reactions to BCG
  • Patients unable to retain solution in bladder for desired indwelling time
  • Taking antibiotics with a name ending in “–floxacin”

Share Facebook Twitter LinkedIn Email Get useful, helpful and relevant health + wellness information enews

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

A Deeper Look Into a 40-Year-Old Bladder Cancer Treatment: Bacillus Calmette-Guerin

While immunotherapy seems to only be a recent trend in the treatment landscape for a variety of cancers, one type was actually used to treat superficial bladder cancer more than 40 years ago – and it is still used in some non-invasive bladder cancers today.
Bacillus Calmette-Guérin (BCG) therapy is a type of immunotherapy used to treat patients with high-risk non-muscle-invasive bladder cancer after transurethral resection.
CURE spoke with Matthew Mossanen, M.D., from the Division of Urology at Brigham and Women’s Hospital, about what BCG is and what patients should know about this treatment option.
In simple terms, can you explain what BCG is and how it works in bladder cancer?
BCG is a type of immunotherapy for bladder cancer. It really started getting used for bladder cancer in the 1970s or so, and it was used in other cancers earlier than that. So, what we have done in urology is basically take a strain of bacteria and weakened it to use for bladder cancer.
The mechanism, or the way it works, is that you create a liquid with the medicine, and put it inside the bladder. And when it is in the bladder, it actually activates the patient’s immune system, turning on the immune cells – the T cells specifically – and it attacks the abnormal cells in the bladder that are cancerous. In that regard, it is a really clever design because you can put BCG in to the bladder and it activates the immune system, but the bladder itself serves as the perfect barrier to prevent it from getting in to the body. It is a really great treatment for patients with non-muscle invasive bladder cancer.
In bladder cancer, which group of patients should be treated with BCG?
BCG is a good option for patients with non-muscle invasive bladder cancer. The diagnoses that we can think about when we want to use BCG are carcinoma in situ (CIS), high-grade disease or patients with T1 disease, and in cases of patients who have disease that is categorized as intermediate- or high-risk disease.
It is one of the most well studied treatments. In each case, every patient and diagnosis are unique. So, it is very important to talk to your urologist about it if you do have high-risk non-muscle invasive bladder cancer.
Are there any notable side effects from BCG patients should be aware of? If so, what should patients be on the lookout for?
Because it is a medicine that is going in to the bladder, it can impact the bladder. So, patients may have symptoms while they are on therapy. The key is to communicate with your doctor, so you can work together to manage them.
Some things that can happen are cystitis, which is like a bladder infection; a urinary tract infection; dysuria, which is kind of like burning; hematuria, which is blood in urine; and some patients just kind of feel a little tired or have some low-grade fevers. Usually we can manage these side effects with medications, and hopefully they get better in a day or so.
In certain situations, there are more serious side effects, and those are some of the things we worry about sometimes. One sign to really watch out for is a fever greater than 101. We also worry sometimes that BCG can maybe get in to the blood stream, and that can cause a serious infection. And if that is the case, usually you should either call your doctor or go to the emergency room right away because you might need blood tests to check your blood for an infection followed by strong, broad-spectrum antibiotics that help control the situation.
How does BCG compare with other bladder cancer treatments? Are there any limitations?
It’s a great therapy for the majority of patients that get it. So, the good news is that many patients will have an initial response that is favorable. The cancer will respond. But there are some limitations in that, while BCG can reduce the cancer recurrence rate, which is cancer coming back, or progression, which is cancer getting worse, it is not perfect. So, one of the limitations of that is that some people, we say “fail” BCG therapy, which just means the cancer continues to come back or continues to grow. And we worry about that because then it can spread, and that can be dangerous. So, one of the limitations is to realize that it is not a perfect treatment.
Are there any trials evaluating BCG right now?
That is a great question, and fortunately is has an exciting answer. Non-muscle invasive bladder cancer is a really complex disease. Right now, researchers are looking at using BCG in combination with other therapies in the bladder or vaccinations. Beyond BCG, researchers are also looking at studying different ways of treating these patients using things like genetic therapy, oral or IV immunotherapy, radiation and a number of other agents. There are a number of clinical trials in progress.
It is also important and exciting to know that there is a lot going in to biomarkers, or ways to predict who will have a response to these medications by looking at either a blood or urine test. So, right now is a very exciting time in bladder cancer because of a lot of active research going on in this space.
What is one key area that patients should know about with BCG?
It is important to realize that if you have non-muscle invasive bladder cancer, this can be an effective treatment. It’s not perfect, but it should definitely be discussed with your urologist. If you do get treatment, you should be followed closely afterwards. So, the takeaway point is that BCG is one step in your treatment, and after you receive it, you still need to see the urologist regularly for ongoing surveillance, which includes cystotomies.

Bacillus Calmette Guerin (BCG) Treatment for Non-Muscle Invasive Bladder Cancer

What is BCG (Bacillus Calmette-Guerin) treatment for non-muscle invasive bladder cancer?

BCG (bacillus Calmette-Guerin) is an intravesical immunotherapy using a bacteria of Mycobacterium bovis (bovine TB) that has been reduced to cause less harm to the body. The bacteria is still kept viable (or “live”) so that it can actively work in the body to kill the cancer cells.

Intravesical is a way in which a medication is put into the bladder. Liquid drugs are put directly into the bladder through a catheter.

BCG is used as a therapy for and protection against bladder cancers that come back after a period of time in patients that have a more aggressive bladder cancer diagnosis. It is currently the most effective treatment.

Share Facebook Twitter LinkedIn Email Get useful, helpful and relevant health + wellness information enews

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Intravesical Therapy for Bladder Cancer

With intravesical therapy, the doctor puts a liquid drug right into your bladder rather than giving it by mouth or injecting it into your blood. The drug is put in through a soft catheter that’s put into your bladder through your urethra. The drug stays in your bladder for up to 2 hours. This way, the drug can affect the cells lining the inside of your bladder without having major effects on other parts of your body.

When is intravesical therapy used?

After TURBT

Intravesical therapy is commonly used after transurethral resection of bladder tumor (TURBT). It’s often done within 24 hours of the TURBT procedure. Some experts say it should be done within 6 hours. The goal is to kill any cancer cells that may be left in the bladder.

To treat non-invasive bladder cancer

These cancers are only in the lining of the bladder. They may be called non-invasive (stage 0), or minimally invasive (stage I) bladder cancers. They have not spread into deeper layers on the bladder wall muscles or to other parts of the body. Intravesical chemotherapy is used for these early-stage cancers because drugs given this way mainly affect the cells lining the inside of the bladder. They have little to no effect on cells elsewhere. This means that any cancer cells outside of the bladder lining, including those that have grown deeply into the bladder wall, are not treated by intravesical therapy. Drugs put into the bladder also can’t reach cancer cells in the kidneys, ureters, and urethra, or those that have spread to other parts of the body.

One dose of intravesical chemotherapy might be the only treatment needed for non-invasive cancers.

Low-risk non-invasive (low-grade) bladder cancers grow slowly. They may be treated with 1 dose of intravesical chemo after TURBT. It’s used to help keep the cancer from coming back.

Intravesical chemotherapy or immunotherapy may used for intermediate non-invasive bladder cancers. Some studies suggest that immunotherapy works best. It’s done once a week for 6 weeks, and may be repeated for another 6 weeks if needed. This is called induction therapy. After a 4- to 6-week break, maintenance treatments are then done for at least 1 year.

High-risk non-invasive bladder cancers might be fast-growing (high-grade), big, or there may be more than 1 tumor. They’re treated with induction intravesical immunotherapy. If there’s a good response to induction therapy, it’s followed by 3 years of maintenance intravesical immunotherapy.

Intravesical immunotherapy maintenance treatment schedules vary. For instance, treatment may be done for 3 to 6 weeks every month, every 3 months, or twice a year. It can be done for 1 to 3 years. Your doctor will talk with you about the best plan based on the details of your bladder cancer and how it responds to treatment.

To treat higher-stage, invasive bladder cancers

One dose of intravesical chemotherapy is done within 24 hours of TURBT. But other types of treatment are usually the next steps for Stage II to IV (2 to 4) bladder cancers because they have spread beyond the lining layer of the bladder wall.

Sometimes induction and maintenance intravesical immunotherapy is used after radiation and systemic (in the blood) chemo for stage II cancers if surgery can’t be done. It’s seldom used for stage III. When it is, it’s used along with other treatments in cases where surgery can’t be done. Stage IV bladder cancers are rarely treated with intravesical therapy.

Types of intravesical therapy

There are 2 types of intravesical therapy:

  • Immunotherapy
  • Chemotherapy

Intravesical immunotherapy

Immunotherapy causes the body’s own immune system to attack the cancer cells.

Bacillus Calmette-Guerin or BCG is the most common intravesical immunotherapy for treating early-stage bladder cancer. It’s used to help keep the cancer from growing and to help keep it from coming back.

BCG is a germ that’s related to the one that causes tuberculosis (TB), but it doesn’t usually cause serious disease. BCG is put right into the bladder through a catheter. It reaches the cancer cells and “turns on” the immune system. The immune system cells are attracted to the bladder and attack the bladder cancer cells. BCG must come in contact with the cancer cells to work. This is why it’s used for intravesical therapy.

Treatment with BCG can cause a wide range of symptoms. It’s common to have flu-like symptoms, such as fever, achiness, chills, and fatigue. These can last for 2 to 3 days after treatment. It also commonly causes a burning feeling in the bladder, the need to urinate often, and even blood in the urine. Rarely, BCG can spread into the blood and through the body, leading to a serious infection. This can happen even years after treatment. One sign of this can be a high fever that isn’t helped by Tylenol or medicines like it. If this happens, call your doctor right away. You might want to ask about other serious side effects you should watch for and call your doctor about.

Intravesical chemotherapy

For this treatment, chemotherapy (chemo) drugs are put right into the bladder through a catheter. These drugs kill actively growing cancer cells. Many of these same drugs can also be given systemically (usually into a vein) to treat more advanced stages of bladder cancer. Intravesical chemotherapy is most often used when intravesical immunotherapy doesn’t work. It’s seldom used for more than 1 year.

The chemotherapy solution might be heated up before it’s put into the bladder. Some experts believe that this makes the drug work better and helps it get into the cancer cells. When the chemo is heated, it might be called hyperthermic intravesical therapy.

Mitomycin is the drug used most often for intravesical chemotherapy. Delivery of mitomycin into the bladder along with heating the inside of the bladder, a treatment called electromotive mitomycin therapy, may work even better than giving intravesical mitomycin the usual way.

Gemcitabine may cause fewer side effects than mitomycin and is less likely to be absorbed into the blood.

Valrubicin might be used if BCG stops working. But not all experts agree on this treatment.

The main side effects of intravesical chemo are irritation and a burning feeling in the bladder, and blood in the urine.

A major advantage of giving chemo right into the bladder instead of injecting it into the bloodstream is that the drugs usually do not reach and effect other parts of the body. This helps people avoid many of the side effects linked to chemo.

BCG intravesical

Generic Name: BCG intravesical (bee cee jee)
Brand Name: Tice BCG Live (for intravesical use), Tice BCG Vaccine, Theracys 3, TheraCys, BCG Vaccine (obsolete)

Medically reviewed by Drugs.com on Nov 6, 2018 – Written by Cerner Multum

  • Overview
  • Side Effects
  • Dosage
  • Professional
  • Interactions
  • More

What is BCG?

BCG (Bacillus Calmette and Guérin) is a freeze-dried product made from bacteria. BCG increases certain white blood cells that destroy invading tumor cells in the bladder.

BCG is used to treat bladder cancer that is localized (has not spread to other parts of the body).

BCG may also be used for purposes not listed in this medication guide.

Important Information

You should not receive BCG if you have tuberculosis, a fever, a bladder infection, blood in your urine, or a weak immune system (caused by disease or by using certain medicines).

You should also not receive BCG if you have had a bladder biopsy, surgery, or catheter within the past 14 days.

Serious and sometimes fatal infections may occur during treatment with BCG. Call your doctor right away if you have signs of infection (fever, chills, body aches).

Before taking this medicine

You should not receive BCG intravesical if you are allergic to BCG, or if you have:

  • tuberculosis;

  • a weak immune system from diseases such as AIDS, leukemia, or lymphoma;

  • a fever, a bladder infection, or blood in your urine;

  • if you are using steroids or receiving chemotherapy or radiation treatments; or

  • if you have had a bladder biopsy, surgery, or catheter within the past 14 days.

Tell your doctor if you have any type of bacterial, fungal, or viral infection (including HIV).

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

You should not breast-feed while being treated with BCG.

How is BCG given?

BCG is injected directly into the bladder using a catheter inserted into the urethra (the tube for passing urine out of your bladder). You will receive this medicine in a clinic or hospital setting.

BCG is usually given once every week for 6 weeks, and then given every 3 to 6 months for up to 2 years. Follow your doctor’s instructions about your specific dosing schedule.

You will need hold the medicine in your bladder as long as possible up to 2 hours. During that time you may be encouraged to lie down or stay relaxed.

For at least 6 hours after you are treated with BCG, your urine will still contain some of the medication and the bacteria it is made from. To prevent the spread of this bacteria, use a toilet rather than a urinal, and sit on the toilet while urinating.

Before you flush the toilet, disinfect the urine with household bleach in an amount that is approximately equal to how much you have urinated. Pour the bleach into the toilet in which you urinated, let it stand for 15 minutes and then flush.

Your doctor may ask you to drink extra fluids for several hours after your BCG treatment to help flush out your bladder. Follow all instructions.

Call your doctor right away if you have a fever after receiving BCG, especially if the fever lasts for several hours or longer.

This medicine can affect the results of certain medical tests. Tell any doctor who treats you that you are using BCG.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your BCG treatment.

What happens if I overdose?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid while receiving BCG?

BCG intravesical can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient’s body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

BCG side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with BCG.

Call your doctor at once if you have:

  • fever, chills, aches, weakness, flu-like symptoms;

  • cough or trouble breathing;

  • pain or burning when you urinate;

  • a weak stream of urine, trouble emptying your bladder;

  • blood in your urine, dark urine;

  • vomiting, upper stomach pain;

  • jaundice (yellowing of your skin or eyes); or

  • signs of a penis infection–burning, itching, odor, discharge, pain, tenderness, redness or swelling of the genital or rectal area, fever, not feeling well.

About 4 to 6 hours after treatment, you may have bladder symptoms such as sudden urges to urinate, frequent urination, stomach discomfort, bloating, and possibly loss of bladder control. Tell your doctor right away if these side effects last for longer than 2 or 3 days.

Common side effects may include:

  • increased urination;

  • painful urination;

  • fever; or

  • flu symptoms.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect BCG?

If you have an infection that must be treated with an antibiotic, you may need to stop receiving BCG for a short time. Antibiotics can make BCG less effective and should be avoided during your treatment with BCG. Follow your doctor’s instructions and be sure to tell any other doctor who treats you that you are receiving BCG.

Tell your doctor about all your other medicines, especially

  • an antibiotic;

  • chemotherapy or radiation;

  • medicine to prevent organ transplant rejection; or

  • medicines to treat multiple sclerosis, psoriasis, rheumatoid arthritis, or other autoimmune disorders.

This list is not complete. Other drugs may affect BCG, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2018 Cerner Multum, Inc. Version: 4.01.

Medical Disclaimer

More about bcg

  • Side Effects
  • During Pregnancy
  • Dosage Information
  • Drug Interactions
  • 1 Review
  • Drug class: miscellaneous antineoplastics

Consumer resources

  • BCG (Intravesical)
  • BCG Vaccine (Immunization)
  • Bacillus of calmette and guerin vaccine, live Intradermal (Advanced Reading)
  • Bacillus of calmette and guerin vaccine, live Intravesical (Advanced Reading)

Other brands: Tice BCG, TheraCys

Professional resources

  • BCG (Intravesical) (Wolters Kluwer)
  • … +2 more

Related treatment guides

  • Urinary Tract Tumors
  • Tuberculosis, Prophylaxis

About the author

Leave a Reply

Your email address will not be published. Required fields are marked *