Monday, January 23, 2023

Bcg Used In Bladder Cancer

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Important Message About The Bcg Shortage

BCG dosing for bladder cancer: Standard frequency schedule correct

Bacillus Calmette-Guérin is a standard treatment option for non-muscle invasive bladder cancer. Last year, Merck & Co., the only maker and supplier of BCG to the United States, informed the AUA they were experiencing a global shortage of BCG due the growing use and need for this product around the world.

While Merck has raised their production of BCG, they expect this shortage to carry through 2020.

Please read the message below from the AUA concerning the shortage.

Role In Carcinoma In Situ

Prior to the development of BCG immunotherapy, 52% of patients with carcinoma in situ would go on to develop muscle-invasive disease. The beneficial role of BCG in CIS of the bladder was demonstrated in a study showing a 71% complete response, again using a 6-week instillation course. A large, randomized controlled trial by the South West Oncology Group comparing induction plus a 3-week maintenance course versus induction alone using intravesical BCG in CIS showed a clear advantage of the former regimen. The addition of a 3-week maintenance course beginning at 3 months produced a complete response rate of 84% and, with ongoing 3-monthly installations, over 70% of those who responded remained disease-free for over 5 years.

What Agents Are Used In Immunotherapy

  • The Ipilimumab is a type of monoclonal antibodies.
  • Opdivo is a type of anti-inflammatory.
  • The anti-PD-1 drug Keytruda is available through Pembrolizumab.
  • The Atezolizumab is a type of anti-inflammatory.
  • The drug Avelumab is available.
  • Imfinzi is a drug that works by blocking the action of the immune system.
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    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.

    Box : Prognostic Factors For Recurrence

    BCG treatment for bladder cancer: What to know
    • Number of tumours more tumours mean more frequent recurrences.

    • Previous recurrence rate* or a recurrence at three months.

    • Size of the tumour those > 3 cm carry a worse prognosis.

    • Grade of anaplasia.

    • Presence of CIS.

    *The recurrence rate being the number of positive cystoscopies per year over the number of cystoscopies performed per year.

    For progression, tumour grade is the most important factor. It is also known that T1 tumours have a worse prognosis than Ta tumours. Using these factors patients with superficial bladder cancer can be divided into three groups: the lowest risk group with a single less than 3 cm Ta G1 tumour, and a recurrence rate of less than one tumour per year a high risk tumour of T1 G3, multifocal, large, highly recurrent, and CIS and other tumours of intermediate risk. Recent studies further confirm these criteria.

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    Treating Stage Iv Bladder Cancer

    These cancers have reached the pelvic or abdominal wall , may have spread to nearby lymph nodes , and/or have spread to distant parts of the body . Stage IV cancers are very hard to get rid of completely.

    Chemotherapy is usually the first treatment if the cancer has not spread to distant parts of the body . The tumor is then rechecked. If it appears to be gone, chemo with or without radiation or cystectomy are options. If there are still signs of cancer in the bladder, chemo with or without radiation, changing to another kind of chemo, trying an immunotherapy drug, or cystectomy may be recommended.

    Chemo is typically the first treatment when bladder cancer has spread to distant parts of the body . After this treatment the cancer is rechecked. If it looks like it’s gone, a boost of radiation to the bladder may be given or cystectomy might be done. If there are still signs of cancer, options might include chemo, radiation, both at the same time, or immunotherapy.

    In most cases surgery cant remove all of the cancer, so treatment is usually aimed at slowing the cancers growth and spread to help people live longer and feel better. If surgery is a treatment option, it’s important to understand the goal of the operation whether it’s to try to cure the cancer, to help a person live longer, or to help prevent or relieve symptoms from the cancer.

    Because treatment is unlikely to cure these cancers, many experts recommend taking part in a clinical trial.

    What To Know About Bcg For Bladder Cancer

    Did you know May is Bladder Cancer Awareness Month? It’s a time to raise extra awareness and promote facts about this disease. Education and raising awareness about bladder cancer is an important part of moving closer to a cure.

    If you or a loved one is diagnosed with bladder cancer it can be frightening. However, your doctor and medical team are there to help you.

    Talk with your healthcare team about all the available forms of treatment. They will tell you about possible risks and the side effects of treatment on your quality of life.

    Your options for treatment will depend on how much your cancer has grown. Your urologist will stage and grade your cancer and assess the best way to manage your care considering your risk. Treatment also depends on your general health and age. Visit our condition article to learn more about treatment options for bladder cancer.

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    Evidence For Reduction Of Recurrence Of Bladder Cancer By Bcg

    There is now a large body of evidence demonstrating the superior efficacy of BCG in the treatment of bladder cancer when compared with TUR alone or TUR and chemotherapy. The European Association of Urology guidelines on NMIBC in 2013 report a total of five meta-analyses to substantiate this claim. In addition, there have been individual randomized controlled trials comparing BCG with epirubicin and IFN, mitomycin C, and epirubicin alone, all of which showed BCG to be the best agent with respect to preventing recurrence.

    Origin Of Bcg And Its Relationship With Bladder Cancer

    Management of BCG Unresponsive Cystectomy Ineligible Bladder Cancer Patients Pembrolizumab

    Mycobacterium bovis Bacillus Calmette-Guérin is a species originated after 230 recultures of the pathogen M. bovis. Over a period of thirteen years, Albert Calmette and Camille Guérin recultured isolated colonies from the originally pathogenic M. bovis. In 1921, they demonstrated that the obtained bacillus was not only non-pathogenic in animal models but also protected against tuberculosis challenge in vaccinated animals. Afterwards, the massive production of BCG was initiated for use in tuberculosis prevention in humans, and it is still the only commercially available vaccine against tuberculosis. At that time, the use of a mixture of two bacteria, Serratia marcescens and Streptococcus pyogenes, was investigated for cancer treatment, and the possibility to use the newly developed and safe BCG offered a novel therapeutic option for some cancer patients. Although some studies demonstrated the potential efficacy of the new BCG as a treatment for diverse types of cancer, it was not until the 1970s that BCG was approved as an immunotherapeutic treatment for bladder cancer patients.

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    History Of Usage Of Bcg

    Tuberculosis was noted to have an antitumour effect at the start of the 20th century. It was Pearl, who in an autopsy series at the Johns Hopkins Hospital in 1929 reported a lower frequency of cancer in patients with tuberculosis. In the 1930s the use of BCG as a cancer therapy was first raised, but enthusiasm for this did not mount until the 1950s and 1960s. In 1969, Mathe et al produced a paper on the treatment of lymphoblastoid leukaemia with BCG, which produced promising results, but unfortunately others could not reproduce their results. This coupled with the development of successful modern chemotherapy and radiotherapy meant enthusiasm for BCG as a treatment waned. Further research carried out by Coe and Feldman rekindled interest in BCG with the demonstration of a strong delayed hypersensitivity reaction to BCG in the guinea pig bladder. This knowledge aided Morales et al who in 1976 carried out the first clinical trial with intravesical BCG. They were able to demonstrate a remarkable decrease in the rates of recurrence of superficial bladder cancer in nine patients. A randomised prospective trial by Lamm et al in 1980 confirmed these earlier observations. Since this time it has been shown that BCG when used has inferred benefit to those with superficial bladder cancer in terms of decreased recurrence rate and increased time to recurrence.

    Treatments For Early Stage Bladder Cancer

    The following are treatment options for bladder cancer. Early stage bladder cancer is only in the inner lining or thin connective tissue layer of the bladder . This includes stage 0a, stage 0is and stage 1 bladder cancers. Your healthcare team will suggest treatments based on the . They will work with you to develop a treatment plan.

    Sometimes bladder cancer comes back after it has been treated or initial treatments dont work. If the cancer is still non-invasive or non-muscle invasive, the following treatments can be used.

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    When To See A Doctor

    There are a few side effects that can be especially dangerous, so make sure to talk to your doctor if you notice that you:

    • Have a severe skin rash
    • Are wheezing or having difficulty breathing
    • Are finding swallowing to be difficult
    • Have a high fever that isnt lowered with Tylenol or other over-the-counter fever reducers

    Bcg And Safety At Home

    BCG treatment for bladder cancer: What to know
    • For the first six hours after BCG treatment, sit down on the toilet when urinating to avoid splashing. Pour 2 cups of household bleach into the toilet bowl. Wait 15 minutes before flushing and wipe the toilet seat with bleach.
    • If you are wearing incontinence pads, take care when disposing of them. Pour bleach on the used pad, allow it to soak in, then place the pad in a plastic bag. Seal the bag and put it in your rubbish bin. You may be able to take it back to the hospital or treatment centre for disposal in a biohazard bin.
    • If any clothing is splashed with urine, wash separately in bleach and warm water.
    • For a few days after treatment, wash your hands extra well after going to the toilet, and wash or shower if your skin comes in contact with urine.
    • Speak to your doctor or nurse if you have any questions.

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    Treatment Of Bladder Cancer By Stage

    Most of the time, treatment of bladder cancer is based on the tumors clinical stage when it’s first diagnosed. This includes how deep it’s thought to have grown into the bladder wall and whether it has spread beyond the bladder. Other factors, such as the size of the tumor, how fast the cancer cells are growing , and a persons overall health and preferences, also affect treatment options.

    Availability Of Data And Materials

    The datasets supporting the conclusions of this article are available in the National Health Insurance Research Database, Taiwan .

    Only citizens of the Republic of China who fulfill the requirements of conducting research projects are eligible to apply for the National Health Insurance Research Database . The use of NHIRD is limited to research purposes only. Applicants must follow the Computer-Processed Personal Data Protection Law and related regulations of National Health Insurance Administration and NHRI , and an agreement must be signed by the applicant and his/her supervisor upon application submission. All applications are reviewed for approval of data release.

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    Modified Tuberculosis Vaccine As A Therapy For Bladder Cancer

    by Markus Berninger, Max Planck Society

    The human immune system can recognize and eliminate not only germs but also cancer cells. This is why treatments with weakened germs can help the immune system in its fight against cancer. Researchers at the Max Planck Institute for Infection Biology in Berlin have genetically modified the tuberculosis vaccine BCG in a way that it stimulates the immune system more specifically. Consequently, the new vaccine offers much greater protection against tuberculosis. A clinical study with patients suffering from cancer of the bladder has now shown that a therapy with VPM1002 could successfully prevent the recurrence of tumors in almost half of the patients who had not responded previously to the BCG therapy. The results could lead to the early approval of the drug for the treatment of cancer of the bladder so that as many patients as possible can profit from this quickly.

    At the end of the 19th century, doctors observed that the tumor in some cancer patients shrank if the patients suffered from a bacterial infection with a high fever. These findings sparked interest in immunotherapy for cancer. Immunomodulatory treatments can specifically stimulate the immune system. As a result, the body’s own immune system is supported in its fight against the tumor, leading to a reduction in the size of the tumor.

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    Infection Of Urothelial Cells

    Bladder Cancer, BCG, and Covid-19 | Treatment Vaccine Update for Patients and Families

    Ratliff demonstrated the role of fibronectin in the attachment of BCG to tumor cells in the late 1980s. BCG is then internalized into the tumor cells, a step that appears to be fundamental to the subsequent immune response. This was demonstrated in experiments where an antifibronectin antibody inhibited the antitumor effect of BCG. In a mouse model, BCG has been found in urothelial cells within 24 hours of instillation. This finding has been supported by in vitro studies in human bladder cancer cell lines.,

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    Induction Of Immune Reaction

    This infection of urothelial cells by BCG leads to stimulation of the local immune response via activation of the reticuloendothelial system. Granulocytes, macrophages, and T-helper cells all appear to facilitate this process. The internalization of BCG, as with other microbes, mediates the antigen-processing functions of antigen-presenting cells. BCG also increases the surface expression of major histocompatibility complex class I in urothelial tumor cells. It is this enhancement of antigen presentation following BCG that suggests a T-cell/major histocompatibility complex pathway is involved in the antitumor response. In mouse bladder carcinoma cells, presentation of antigen to BCG-specific CD4+ T-cells has been demonstrated. These findings support the idea that not only the hosts circulating antigen-presenting cells but also infected bladder tumor cells are involved in initiating the immune response.

    Chemotherapy For Bladder Cancer

    Chemotherapy uses anticancer drugs to destroy cancer cells. It is sometimes used to treat bladder cancer. Your healthcare team will consider your personal needs to plan the drugs, doses and schedules of chemotherapy. You may also receive other treatments.

    Chemotherapy is given for different reasons. You may have chemotherapy to:

    • destroy cancer cells in the body
    • shrink a tumour before other treatments such as surgery or radiation therapy
    • destroy cancer cells left behind after surgery and reduce the risk that the cancer will come back
    • make cancer cells more sensitive to radiation therapy
    • relieve pain or control the symptoms of advanced bladder cancer

    Chemotherapy for bladder cancer that has not grown into the muscle of the bladder wall is given as intravesical therapy, which means that the drugs are placed directly into the bladder. Chemotherapy may also be a systemic therapy given through a needle into a vein. This means that the drugs travel through the bloodstream to reach and destroy cancer cells all over the body, including those that may have broken away from the primary tumour in the bladder.

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    When Is Bcg Treatment Used

    You may have BCG directly into your bladder after surgery to remove non-muscle-invasive bladder cancer. This type of surgery is called a transurethral resection of a bladder tumour .

    This treatment helps prevent the cancer from coming back in the bladder lining. It also reduces the risk of the cancer becoming muscle-invasive. Doctors usually suggest this treatment if you have a high-risk bladder cancer, or sometimes if you have an intermediate-risk bladder cancer.

    There is usually at least 2 weeks between the surgery to remove the cancer and the start of BCG treatment. This is to give your bladder enough time to heal from the surgery.

    You usually have BCG treatment once a week for 6 weeks. This is sometimes called the induction course. You may be offered more BCG treatments. This is usually called maintenance treatment.

    Treatment times vary. Your doctor will explain what is best for you.

    How You Have It

    BCG for intravesical treatment of bladder cancer

    BCG is a liquid. Your doctor or nurse puts the liquid into your bladder through a tube in the urethra . Usually, they then remove the catheter.

    You must not pass urine for 2 hours. This gives the BCG time to be in contact with the lining of the bladder. Some hospitals may ask you to change position every now and again to make sure the drug reaches all parts of your bladder lining.

    When you do pass urine, you need to be careful for 6 hours after the treatment because the vaccine contains bacteria. Men should sit down to pass urine to reduce the chance of splashing.

    After you’ve been to the toilet, pour about half a pint of neat bleach into the toilet bowl and leave it for 15 minutes before flushing.

    Wash your hands and genitals immediately with warm soapy water after you pass urine.

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    Evidence For Prevention Of Progression By Bcg

    As the ability of BCG to prevent tumor recurrence became increasingly well documented, it became less clear how this translated into preventing disease progression or attaching mortality. Several studies have attempted to define whether or not BCG immunotherapy can prevent progression. A meta-analysis by Sylvester et al in 2002 identified a total of 24 trials encompassing 4,863 patients comparing TUR and BCG with either TUR alone or TUR with another non-BCG treatment. This study found a reduction of 27% in the odds of progression in patients treated with BCG if given any period of maintenance therapy. This finding was supported in a meta-analysis by Böhle and Bock in 2004. Their study looked at the outcomes from nine clinical trials including a total of 1,277 patients comparing BCG and mitomycin C. Overall, there was no statistically significant difference in the odds ratio for progression between the two groups however, as determined by Sylvester et al, there was a statistically significant reduction in tumor progression in the subgroup of patients treated with BCG where maintenance therapy was also given.

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