Side Effects Of Immunotherapy
Like all treatments, checkpoint inhibitors can cause side effects. Because these drugs act on the immune system, they can sometimes cause the immune system to attack healthy cells in any part of the body. This can lead to a variety of side effects such as skin rash, diarrhoea, breathing problems, inflammation of the liver, hormone changes and temporary arthritis. Your doctor will discuss possible side effects with you.
To learn more see Immunotherapy.
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New Improvements In Targeted Therapies
Despite the excitement and advancements involving immunotherapies, chemotherapy remains the first-line treatment for advanced bladder cancers. There, too, medical researchers are making progress.
The cells of bladder-cancer tumors contain a high number of surface antigens, which are molecules capable of triggering an immune response. These antigens are the reason immunotherapies can be effective for the treatment of bladder cancer, and these antigens also assist the action of newer chemotherapy medicines known as antibody-drug conjugates. These drugs use these quite clever molecules that have an antibody on one endsomething that will hopefully bind onto the antigens on cancer cells in a selective mannerand a chemotherapy agent on the other, Crabb says.
The big problem with conventional chemotherapy, he explains, is that it struggles to differentiate between normal cells and cancer cells. Fast-growing cells that resemble cancer cellssuch as those of the bone marrow, digestive tract, mouth, and scalptypically draw friendly fire. This is why people on chemo often experience multiple severe side-effects, including hair loss, fatigue, nausea, and sores. Antibody-drug conjugates, by selectively binding to antigens on bladder cancer cells, can reduce this kind of collateral damage. What it does is lock the chemotherapy onto this molecule that exists on top of the cancer cells, which hopefully spares the normal cells the direct exposure to chemotherapy, Crabb says.
Cris Impact In Bladder Cancer
Thanks to groundbreaking advancements in immunology research and clinical trials, immunotherapy has become one of the most promising bladder cancer treatments of our time.
Lloyd J. Old, in partnership with Baruj Benacerraf and Donald Clarke, demonstrated in 1959 that BCG, the tuberculosis vaccine, could inhibit tumor growth in mice. In subsequent years, CRI funded Alvaro Morales of Queens University in Canada, who, in 1980, demonstrated that BCG is effective in the prevention of recurrence of non-muscle invasive bladder cancer in human patients. The FDA approved the use of BCG for superficial bladder cancer in 1990.
In the early 70s my rejection by the National Cancer Institute of Canada to test BCG on superficial bladder tumors included the reviewer comment BCG is not only ineffective and dangerous but a throwback from the stone age of tumor immunology. If I hadnt subsequently applied to and been approved for a grant from CRI, BCG might never have become the standard therapy for the treatment and prevention of early stage bladder cancer.
Other CRI-funded research into bladder cancer includes:
New and developing bladder cancer immunotherapies have the potential to reduce recurrence rates and improve survival rates for patients with bladder cancer. You can explore CRIs current research into bladder cancer in our funding directory.
- Oncolytic Virus Therapy
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Are There Any Possible Effects From The Treatment
9out of 10 people having BCG will develop some side effects these usually beginwithin 3-4 hours after treatment and may last 1-3 days.
You should tell your doctorat your next appointment if you have any of these symptoms.
- Somebladder discomfort â an irritation rather like a urine infection.
- Flu-likesymptoms which can last for 1-3 days after each treatment.
- Wantingto pass urine more often than usual or more urgently, which can last for two tothree days.
- Failureto complete the course of treatment due to discomfort in the bladder.
- Bloodor debris in the urine.
Drinking2 litres of fluid daily, unless advised otherwise, and avoiding tea/coffee for24 hours after treatment will help flush any remaining drug out of the bladderand may ease the above symptoms.
- Narrowing of the urethra following repeated use of a catheter.
- Inflammationwhich can affect various parts of the body .
- Persistentor severe pain after treatment, sometimes leading to removal of the bladder.
- Generalisedand possibly serious infection with the BCG bacteria needing treatment inhospital with powerful antibiotics. This is not TB and there is no risk ofcatching TB from the treatment.
Veryrarely â less than 1 person in every 100 â may experience more serious treatmenteffects.
Contact your GP/Nurse immediately if you have anyof the following:
- Urineis cloudy/offensive smelling
When You Go Home
Some hospitals allow you to go home with the medicine in your bladder if you live close by and are okay with the treatment. Your team will let you know if you can do this. You should follow the advice on what to do when you pass urine.
You need to drink lots of fluid after this treatment for 24 hours. It helps clear your system of the BCG.
You should not have sex for 24 hours after each treatment. During your course of treatment and for a week afterwards, you should wear a condom during sex.
Having bladder cancer and its treatment can be difficult to cope with. Tell your doctor or nurse about any problems or side effects that you have. The nurse will give you telephone numbers to call if you have any problems at home.
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New Course Of Treatment Could Become Standard For Patients With Metastatic Cancer
Immunotherapy after surgery helped reduce cancer recurrence in patients with urothelial cancer of the bladder or other sites in the urinary tract that had invaded the muscle and therefore posed a high risk for recurrence, according to clinical trial results presented at the American Urological Association annual meeting in May.
The results support giving the immunotherapy nivolumab as an adjuvant treatmenta therapy given after surgeryas standard of care for patients who have muscle-invasive urothelial carcinoma. About 700 patients participated in the phase 3, randomized, double-blind trial, named CheckMate 274 half were given nivolumab and the other half placebo after having surgery with chemotherapy beforehand.
Longer-term follow-up data is important for reinforcing the initial results we published last year demonstrating for the first time that immunotherapy administered after surgery for bladder cancer and other urothelial cancer can decrease the risk of cancer recurrence, said lead author and presenter Matthew Galsky, MD, Director of Genitourinary Medical Oncology, Mount Sinai Tisch Cancer Center.Almost 200,000 people die each year of urothelial cancer worldwide, so advances like immunotherapy being used in this manner bring hope.
About the Mount Sinai Health System
Am I Eligible For Immunotherapy
In 2018, the most common question that Emil Lou, M.D., Ph.D., heard from patients with cancer in his clinic at the University of Minnesota was: Am I eligible for immunotherapy?
Most of these patients had seen advertisements for immunotherapy on television or heard a story about a patients tumor melting away, and they wanted to know if they could get immunotherapy, said Dr. Lou, who treats patients with gastrointestinal cancers.
His patients had heard of dramatic and lasting responses to immunotherapy drugs among some patients with advanced cancers.
Although few of his patients have been candidates for immunotherapy based on the genetic features in their tumors, Dr. Lou has discussed the treatmentand possible side effectswhen it has been an option.
In these conversations, he would introduce the idea that immunotherapy drugs have side effects. In that respect, immunotherapy drugs are like all treatments for cancer, he tells his patients. They can cause rashes and joint pain and diarrhea. And in a small percentage of patients, immunotherapy can cause shortness of breath and other more serious complications.
Dr. Lou added, Immunotherapy drugs are not perfect.
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Starting Immunotherapy: What To Expect
The FDA has approved several immunotherapy drugs to treat bladder cancer:
Once you and your doctor decide to start one of these treatments, it helps to know a bit about what you can expect while youâre getting it.
How do you get immunotherapy?
To get immunotherapy, youâll go to a treatment center on a regular schedule to get the medicine through an infusion, a tube that goes into a vein. Your doctor will decide how many rounds of treatment you need.
Your doctor will order some lab tests before and during your treatment to see how your body responds to the drug.
You take the medicine through a tube that goes in one of your veins.
A doctor or nurse will look after you when youâre getting the IV to make sure you donât have any bad reactions or side effects. If you do, your doctor might slow down the infusion or delay or stop the treatment.
Speak up if you feel any of these while youâre getting treatment:
Some immunotherapy drugs can also affect your ability to have children. Talk to your doctor before you start treatment to figure out the options you have if you want to have a baby in the future.
Treating Stage Iii Bladder Cancer
These cancers have reached the outside of the bladder and might have grown into nearby tissues or organs and/or lymph nodes . They have not spread to distant parts of the body.
Transurethral resection is often done first to find out how far the cancer has grown into the bladder wall. Chemotherapy followed by radical cystectomy is then the standard treatment.Partial cystectomy is rarely an option for stage III cancers.
Chemotherapy before surgery can shrink the tumor, which may make surgery easier. Chemo can also kill any cancer cells that could already have spread to other areas of the body and help people live longer. It can be especially useful for T4 tumors, which have spread outside the bladder. When chemo is given first, surgery to remove the bladder is delayed. The delay is not a problem if the chemo shrinks the cancer, but it can be harmful if it continues to grow during chemo. Sometimes the chemo shrinks the tumor enough that intravesical therapy or chemo with radiation is possible instead of surgery.
Some patients get chemo after surgery to kill any cancer cells left after surgery that are too small to see. Chemo given after cystectomy may help patients stay cancer-free longer, but so far its not clear if it helps them live longer. If cancer is found in nearby lymph nodes, radiation may be needed after surgery. Another option is chemo, but only if it wasnt given before surgery.
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Checkpoint Inhibitors Unleash An Immune Attack
Checkpoint inhibitors work by releasing a natural brake that the immune system places on powerful immune T cells so they dont accidentally attack normal cells. Since 2016, four checkpoint inhibitor drugs have been approved for bladder cancer: atezolizumab , pembrolizumab , nivolumab , and avelumab .
The drugs target molecules called PD-1 or PD-L1, which are on the surface of immune T cells or on cancer cells. MSK played a key role in gaining FDA approval for atezolizumab, pembrolizumab, and nivolumab.
MSK genitourinary oncologist Dean Bajorin led a large international clinical trial showing that nivolumab reduces bladder cancer recurrence in people whose disease has spread into the muscle wall. About 25% of bladder cancers fall into this high-risk category, which is harder to treat and much more likely to spread to other parts of the body. The FDA approved nivolumab for this use in 2021.
The absence of good options to treat high-risk disease was frustrating for both patients and doctors, Dr. Bajorin says. Now, for the first time, we can offer a new immunotherapy to reduce recurrence. Its a major advance.
Is Bcg Treatment Contagious
Because BCG contains live bacteria, precautions are necessary to prevent it from being passed to others.
Patients should go to the bathroom sitting down to reduce splashing and wash their hands thoroughly after urinating. Pouring bleach into the toilet after use may also prevent contamination.
Once home, a patient should drink plenty of liquids and avoid sexual contact with others for 24 hours.
Research has shown that BCG may also reduce the risk of contracting a respiratory tract infection, giving your immune system a boost. However, precautions are still necessary to stay healthy.
The care team will talk to the patient about what to expect and provide instructions to follow at home.
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Mabs Not Directed At Immune Checkpoints
Several nonimmunotherapy mAbs are also being investigated in multiple studies of solid tumors, including bladder cancer: anti-CEA antibody MK-6018 in advanced or recurrent cancers including bladder cancer antibody-drug conjugate HuMax targeting tissue factor anti-FGFR3 antibody B-701 and ramucirumab , a VEGFR2 mAb, and chemotherapy .
The Current Burden Of Urothelial Carcinoma
Bladder cancer, or urothelial carcinoma, is the fourth most common cancer in men and the eighth most common cancer in women in the United States . The American Cancer Society estimates 79030 new cases and 16870 deaths from urothelial carcinoma in 2017 . Clinically, urothelial carcinoma can be divided into nonmuscle-invasive bladder cancer , muscle-invasive bladder cancer , and metastatic urothelial carcinoma .
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Checkpoint Inhibitors And Bladder Cancer
Long-term survival for people diagnosed with advanced bladder cancer is poor, with approximately 5% of patients with metastatic bladder cancer surviving for 5 years or more.
Checkpoint inhibitors have shown activity in patients with metastatic bladder cancer in both the second-line setting and the first-line setting , explained Andrea B. Apolo, M.D., who heads the Bladder Cancer Section in NCIs Center for Cancer Researchs Genitourinary Malignancies Branch.
But we still needand are awaitingthe results of ongoing randomized trials comparing checkpoint inhibitors and chemotherapy in the first-line setting for patients with metastatic bladder cancer, she continued. The results will allow us to adequately compare patient outcome in terms of survival and quality of life with these therapies.
With the exception of pembrolizumab, the drugs covered by these approvals target a protein known as PD-L1 that is expressed at high levels on some cancer cells. Pembrolizumab targets PD-1, the receptor protein for PD-L1, on immune cells. Normally, binding of PD-L1 to PD-1 tamps down immune activity. By preventing the interaction between PD-L1 and PD-1, all four drugs can allow the immune system to be more active against tumor cells.
The other checkpoint inhibitor approved by the FDA for the treatment of patients with bladder cancer, nivolumab , targets PD-1.
If Your Immunotherapy Stops Working
Immunotherapy may not work for everyone who takes it. If youÃ¢ve tried it and it didnÃ¢t stop your cancer, you still have a few options. What kind of treatment you get next depends on what others youÃ¢ve tried and what stage your cancer is in.
This treatment uses powerful drugs to kill cancer. Even if youÃ¢ve already tried some drugs before or along with your immunotherapy, your doctor may try other ones or different combinations of medicines to fight your cancer. Chemo drugs for the most common form of bladder cancer include:
YouÃ¢ll get chemotherapy in cycles with a few weeks in between to give your body time to recover.
If you still have all or part of your bladder, your doctor might recommend an operation called a radical cystectomy. Your doctor will take out all of your bladder and the lymph nodes nearby. They might also remove some of your reproductive organs. For men, that could be the prostate gland and seminal vesicles. For women, it might be the ovaries, fallopian tubes, uterus, cervix, and a small part of the .
If you think you might want to join a clinical trial, your doctor will help you make the decision. They will talk about:
- How the new treatment is different from the usual treatments you could get
- What the risks are
- Any tests youÃ¢ll need
- How often youÃ¢ll get treatment
YouÃ¢ll be able to leave the clinical trial whenever you want, for whatever reason you might have.
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New Immunotherapy Drugs Are Making Headway In The Treatment Of Bladder Cancer
Bladder cancer is the fourth most common cancer in men, and is less common in women. According to the American Cancer Society, about 79,030 new cases of bladder cancer will be diagnosed in 2017. Urothelial carcinoma is the most common type of bladder cancer. Urothelial carcinomas start in the urothelial cells that line the inside of the bladder. Other, less common types of bladder cancers include squamous-cell carcinoma, adenocarcinoma, small-cell carcinoma, and sarcoma.
Bladder cancer can often be found early, because some of its symptoms are obvious, such as blood in the urine as in all cancers, the earlier bladder cancer is detected, the earlier treatment can begin, and the greater likelihood for survival.
Until recently, treatment options for bladder cancer included surgery, chemotherapy, radiation therapy, and Bacillus Calmette-Guérin , which is an older type of immunotherapy that is made of a bacteria that can help stimulate the immune system. Before the FDA approval of new immunotherapy drugs, BCG was the main treatment used for bladder cancer.
The past year, from May 2016 to May 2017, was a watershed period for new immunotherapy treatments for bladder cancer. After decades of no new treatments approved by the FDA for this type of cancer, 5 new immunotherapies were approved in a span of 12 months for bladder cancer.
Infection Of Urothelial Cells
Ratliff demonstrated the role of fibronectin in the attachment of BCG to tumor cells in the late 1980s.16 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.17 In a mouse model, BCG has been found in urothelial cells within 24 hours of instillation.18 This finding has been supported by in vitro studies in human bladder cancer cell lines.19,20
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