Lamm DL, Crawford ED, Blumenstein B, Crissman JD, Montie J, Gottesman J, Tice substrain . Avoid exposing BCG to direct sunlight. Herr HW, Pinsky CM, Willet FW, Sogani PC, Oettgen HF and Melamed MR: Hillyard RW Jr, Ladaga L, and Schellhammer PF, Superficial Transitional. Common side effects of BCG include flu-like symptoms, fatigue, fever, chills, or bladder irritation. 139:290-293, 1988. In my comparison TICE BCG using a monthly maintenance schedule with mitomycin C, 55% had complete response vs 44% CR with mitomycin (Urol. If disease progression occurs, or grade 3 disease is present after 6 months of BCG treatment, cystectomy is generally recommended. If symptoms respond within one week, isoniazid can be discontinued after the second or third week. One drop of the BCG suspension to be given intravesically can be placed on the cleansed inner thigh and the skin punctured four times with a 28g needle (Tine technique). BCG treatment for non-invasive bladder cancer BUI Protocol. Lamm DL, Sardosdy MF, Grau DA, Buchanan J, Hunt J, and DeHaven J: Lamm DL, Blumenstein BA, Crawford ED, et al: A randomized trial of. Single instillations have been demonstrated to be effective with Thiotepa, Adriamycin (50mg/50cc), Mitomycin (20mg/20cc), and Epirubicin, even in these “low risk” patients. The table on the next page shows the schedule of BCG … Occasionally higher doses of prednisone are required. Lamm DL, Morales A, Grossman HB, Lowe B, Swerdlow R, Ebert R, Habicht %���� Technique of BCG Maintenance. Oncol. The criteria for increased risk were 2 or more episodes of tumor within the most recent year, or 3 or more tumors within 6 months. JT Leimert, ED Crawford, U Kosecka, and R Wittes. Conclusions: Compared to standard induction therapy maintenance BCG immunotherapy was beneficial in patients with carcinoma in situ and select patients with Ta, T1 bladder cancer. Photodynamic These guidelines aim to describe the optimal condition to perform intravesical instillation of BCG or mitomycin C in order to increase its oncologic efficiency and to decrease its morbidity. << BCG x6         x3x3  x3  x3 x3  x3         x3 x3x3x3 x3 x3 x3 x 1992;147:596. Thus, strict adherence to the protocol for canceling the BCG in the presence of infection, and aborting the instillation in the setting of trauma and/or any degree of gross hematuria, is required. Prostatic Urethra: Results of Treatment With Intravesical Bacillus To decrease the chance of pyelovenous backflow, a manometer is used in a manner analogous to Renacidin irrigation. Though a major component of this reaction is hypersensitivity, prednisone alone without isoniazid and rifampin should not be given. The most commonly used agents are BCG (Bacillus Calmette-Guérin) and Mitomycin C. It is theorised that BCG stimulates an inflammatory response that promotes malignant cell kill by immunocompetent cells. 12. Intravesical BCG can eradicate TCC in the prostatic urethra. Symptoms should last no more than 2 days. Certaines des équipes qui utilisent la BCG thérapie d'entretien ont même changé de protocole au fil du temps. OncoTICE BCG 12.5mg per vial containing 2-8 x 10 8 CFU Tice BCG.. After reconstitution in 50 ml saline the suspension contains 0.4-1.6 x 10 7 CFU/ml.. OncoTICE is a freeze-dried preparation containing attenuated bacilli of Mycobacterium bovis, prepared from a culture of Bacillus Calmette-Guérin (BCG). That is why we always reduce the dose (1/3, 1/10, 1/100th even if needed) or hold treatment if increasing side effects are seen. With serious infections triple antibiotic therapy may be needed, and ethambutol 1200mg daily or a fluoroquinolone may be added. For a print-friendly version of the following material, click here, A simplified summary of the protocol is also found below 3. Induction round of six weekly instillations. 7. In patients with CIS, Grade 3, or stage T1 disease I therefore recommend continuation of three week maintenance at years 4, 5, 6, 8, 10, and 12. In my comparison of 6 week induction BCG (Connaught) vs three-week maintenance, complete response was increased from 68% to 84%. Caution must be taken to taper the prednisone slowly because hypotension may return when prednisone is stopped. In patients with CIS treated with BCG, the incidence of TCC in the upper ureter is likely to be higher than the 25% reported by Herr in his combined series that included patients without CIS. 1988. There is no need to repeat cystoscopy until at least 4-6 weeks after completion of the 6-week induction course. Introduction: Intravesical BCG immunotherapy and mitomycin C are considered as the standard treatment for non-muscle invasive bladder cancer. superficial bladder cancer. %PDF-1.4 CONCLUSION: Stimulation of the immune system with 3-week maintenance BCG appears to reduce the incidence of subsequent malignancy, particularly carcinoma of the prostate. The maintenance schedule also significantly reduced disease progression. If symptoms are more severe or prolonged, isoniazid 300mg daily can be used to treat the symptoms. 21. In our animal model, prednisone alone increased mortality, but prednisone plus antibiotics markedly improved survival when compared with antibiotics alone. [���M�ݐ�F�ܑ� #���0�3��d�;�5�S� Thanks to Crilly Butler for the above summary, back to non-muscle-invasive bladder cancer, Badalament RA, Herr HW, Wong GY, et al. However, controversy remains regarding the role of maintenance therapy, and its long-term effect on recurrence and progression. While BCG has been compared to single agent intravesical chemotherapy as first-line therapy, few studies exist comparing BCG to sequential intravesical chemotherapy regimens. The dose is two tablets twice a day (only three a day for persons under 100 lb). Dr. DL Lamm [http://www.bcgoncology.com] has been a pioneer in the field of immunotherapy for bladder cancer since the early ‘80’s. J. Urol. Study. Estimated median time for worsening-free survival, defined as no evidence of progression including pathological stage T2 disease or greater, or the use of cystectomy, systemic chemotherapy or radiation therapy, was 111.5 months in the no maintenance and not estimable in the maintenance arm (log rank p = 0.04). However, these results with a lower level of evidence should be treated with caution. The three week course of BCG is then repeated at 12, 18, 24, 30, and 36 months. BCG pc. BCG is not necessary unless tumor recurrence becomes a problem for these patients. BCG is relatively resistant to cycloserine and pyrazinamide. After confirming reflux with a cystogram, intravesical BCG can then be used to treat the lower ureters. 4 0 obj Therefore, our next study will use percutaneous BCG. If symptoms do not respond or evidence of BCG infection other than local cystitis is present, we treat with isoniazid 300mg plus rifampin 600mg daily for three months (see below). If all clear, wait a week and begin sixth maintenance round of 3 weekly instillations (Month 30) Unused solution is discarded as biohazardous waste after 2 hours. Treatment protocols for bladder cancer are provided below, including those for chemotherapy, immunotherapy, and systemic neoadjuvant and adjuvant therapy. Progression was further significantly reduced(Lamm, J. Urol. 7. I have patients lie on their abdomen for 15 minutes in the office to displace the anterior bubble that enters the bladder as the air is displaced from the catheter. 6. Le BCG : un traitement efficace dans le cancer de la vessie Limiter les rechutes dans le cancer de la vessie, voici l'enjeu d'une étude dirigée par l'équipe de Matthew Albert à l'Institut Pasteur. I generally give a “6 plus 3” course, confirm response with cytology and a nephrostogram, and then pull the nephrostomy tube. The increased toxicity of maintenance BCG has been noted, but other benefits have been largely ignored. Crisman, JE Montie, BA Lowe, MF Sarosdy, RD Bohl, HB Grossman, TM Beck, tel: 602 493 6626. /Producer (pdfFactory Pro 3.51 \(Windows XP Professional French\)) After today's meeting w/ my Urologist, we talked about Tecentriq (just approved May 18, 2016) as replacement for BCG. Intravesical therapy does not eradicate TCC of the distal ureters, and upper tract TCC is most likely to occur in patients with CIS of the bladder. Calmette-Guérin therapy of superficial bladder cancer. Alternatively, BCG can be given via ureteral catheters or intravesically, if reflux to the tumor site is confirmed. Instillation Directions • Insert instillation spike with attached tubing and closed pinch clamp into top of PBS vial. It takes 6 weeks for the optimal immune response to develop in most patients when given the initial course of BCG. In patients who received maintenance BCG, only 25% had recurrence, or 27% fewer than induction BCG (P<0.000001, and 45% and 52% fewer than expected with chemotherapy or surgery alone). J Urol Glashan RW: A randomized controlled study of intravesical alpha-2b The dose amount expressed in milligrams varies according to the BCG substrain; the typical dose of BCG used for intravesical instillation is 1-8 x 10. At the three month evaluation, 192 in each arm were disease free and therefore eligible for evaluation of the benefit of maintenance BCG. Recurrence of TCC in the prostatic urethra is common, and in patients with CIS or high grade TCC must be carefully sought. Introduction: Three-week maintenance BCG, when compared to standard 6-week induction, increases complete response in CIS from 70% to 84%, reduces recurrence of Ta, T1 TCC from 52% to 25% at 8 years, and significantly reduces disease progression/worsening. In my SWOG study of three week maintenance BCG, 14% of patients who had residual CIS at the three month evaluation went on to have complete response by the six month evaluation without further treatment. Urol., Intravesical Immnuotherapy uses a live vaccine called Bacillus Calmette-Guerin (BCG), which is also used to inoculate against Tuberculosis; when this is placed in the bladder it creates a local inflammatory reaction that kills cancer cells. BCG reduces disease progression compared with surgery or surgery plus chemotherapy, and maintenance BCG results in a further significant reduction in progression. the induction-only arm and 24/183 (13%) in the maintenance arm (relative risk 0.68, P=0.014). The preparation, called “Oncovite,” is made by Mission Pharmacal. However, more than 90% of healthy adults will convert to a positive PPD skin test with percutaneous BCG, and a positive PPD increases the complete response in CIS from 49% to 77% (P<0.0001). Two BCG preparations are commercially available in the US: Connaught (TheraCys) and Tice (Organon) BCG. week 1 - 6 Induction BCG; week 12 Rigid cystoscopy after induction; week 14 - 16 Maintenance course 1; week 22 Flexible cystoscopy 1 Intravesical BCG should not be given within one week of bladder tumor resection. Treatments are continued weekly to a total of 6 instillations. Materials and Methods: All patients in the study had transitional cell carcinoma of the bladder with carcinoma in situ or an increased risk of recurrence. Median recurrence-free survival time was twice as long in the 3-week maintenance arm compared to the no maintenance arm, and patients had significantly longer worsening-free survival. TURBT      Cysto  x  x    x   x   x    x           x  x  x  x  x Treatment should be postponed for at least one week following transurethral resection, biopsy, 13. • Transfer appropriate amount of BCG directly into 50 cc vial of PBS/Intron A. This solution is placed into the bladder on a weekly basis and often monthly as a maintenance. If irritative symptoms persist beyond three days, fail to respond to symptomatic treatment, or are severe isoniazid 300mg a day can be given. 2. BCG immunotherapy can be more toxic than Mitomycin chemotherapy. We would like to show you a description here but the site won’t allow us. Overall 5-year survival was 78% in the no maintenance compared to 83% in the maintenance arm. Solsona E, Iborra I, Rirus JV, Dumont R, Casanova JL, and Calabuig C: 1/3 dose BCG weekly for up to 3 weeks beginning at 3 months (that would be 6 weeks after the 6 week induction). endobj /Creator (pdfFactory Pro www.fineprint.fr) Of 307 patients, 25% developed upper tract tumor (median 56 months) and 32% of relapses were fatal. The optimal dosage regimen for adjuvant therapy with intravesical BCG has not been established. Discard syringe with vial venting device. 16:1099,1998). BCG is administered directly into the bladder via a catheter. Wait three months and have cystoscope. ____________________________________________________, MAINTENANCE BACILLUS CALMETTE-GUERIN IMMUNOTHERAPY FOR RECURRENT TA, T1 AND CARCINOMA IN SITU TRANSITIONAL CELL CARCINOMA OF THE BLADDER: A RANDOMIZED SOUTHWEST ONCOLOGY GROUP STUDY, DONALD L. LAMM*†; BRENT A. BLUMENSTEIN; JOHN D. CRISSMAN; JAMES E. MONTIE; JAMES E. GOTTESMAN; BRUCE A. LOWE; MICHAEL F. SAROSDY‡; ROBERT D. BOHL; H. BARTON GROSSMAN§; THOMAS M. BECK; JOSEPH T. LEIMERT; E. DAVID CRAWFORD||, From the West Virginia University Medical Center, Morgantown, West Virginia, Southwest Oncology Group Statistical Center and Swedish Hospital Tumor Institute, Seattle, Washington, Harper Hospital, Detroit and University of Michigan Medical Center, Ann Arbor, Michigan, Oregon Health Sciences University and Northwest Clinical Oncology Program, Portland, Oregon, University of Texas Health Science Center at San Antonio, San Antonio and University of Texas M. D. Anderson Cancer Center, Houston, Texas, Columbus Clinical Oncology Program, Columbus, Ohio, St. Luke’s Regional Medical Center, Boise, Idaho, and University of Colorado, Denver, Colorado THE JOURNAL OF UROLOGY 2000;163:1124-1129 Online at http://www.jurology.com April 2000, p. 1124 By lowering the dose of BCG to 1/3, 1/10/, 1/30, or 1/100th as needed to avoid increased irritative or systemic symptoms, very few patients have any difficulty with BCG immunotherapy. The preparation of BCG suspension must be done using aseptic technique. En 1985, cet auteur a rapporté qu'une instillation tous les 3 mois en plus du traiteme… Maintenance BCG The medications work on the tumour cells on the inner lining of the bladder and help keep the cancer from coming back (recurrence). The policy of withholding maintenance BCG from patients with increased side effects may have diminished the opportunity to observe severe toxicity. See package insert. Unlike cytotoxic chemotherapy, which kills cells by direct contact, BCG kills cells by inducing an immune response. of maintenance versus nonmaintenance intravesical Bacillus A prospective randomized trial 8. MAINTENANCE BCG IMMUNOTHERAPY: EVIDENCE OF ADDITIONAL PROTECTION AGAINST situ (TIS): Its impact on management. J Urol. Immunotherapy Your own body’s immune system cells switch on to Side effects of intravesical therapies. No significant advantage of continued treatment has been demonstrated in controlled studies, but continued treatment (4-6 week) is appropriate for CIS or incomplete resection. Then follow at 4, 5 and 6 years, and then 8, 10 and 12 years. Leimert J and Coltman CA: Maintenance BCG immunotherapy of superficial Most of these patients will have had an induction course of BCG, so three rather than six instillations would be appropriate. BCG maintenance therapy also reduced the incidence of other cancers, primarily prostate cancer. Overall, the recurrence rates for full-dose BCG, one-third dose BCG and one-third dose BCG plus interferon were 50%, 30% and 10% (Pearson’s test, p~O.O3S). For a print-friendly version of this material, click here. With sepsis the current treatment of choice is no longer cycloserine, but isoniazid, rifampin, and prednisone 40mg daily. 8. Thereafter they leave the office and are asked to retain the suspension, if possible, for two hours. Consideration should also be given to transurethral resection of the prostate in these patients to reduce the risk of occult TCC in the prostatic ducts progressing to invasive disease. Badalament RA, Herr HW, Wong GY, et al. The preparation we now use has been modified (improved, we hope) from our original study based on subsequent research. For the latest published findings on maintenance therapy, see abstract below references. Long-term (5-8 year) recurrence is reduced by 7% (Pawinsky A , EORTC/MRC: J Urol. 3. BCG Bladder Instillation Instructions EXPLANATION: BCG is a solution made of the tubercular bacillus developed in such a way that it can be used in the treatment of bladder tumors. interferon in carcinoma in situ of the bladder. at 3 months there would be 3 weekly instillations). J Urol. /Author (tbaril) After 28 years of academic practice, Dr. Lamm has opened a private practice limited to genito-urinary oncology: Important: Avoid contact with BCG vaccin… Wait three months and have cystoscope. K: Keyhole-limpet hemocyanin (KLH) immunotherapy of papillary and in In our SWOG study 660 patients received induction BCG and 550 were randomized to observation vs maintenance BCG. I therefore recommend the three week maintenance schedule (see below). CANCER. DeHaven JI, Traynellis CT, Riggs DR, and Lamm DL: Antibiotic and Steroid Lamm est le premier à avoir suggéré un bénéfice de ce traitement. It is a treatment often used after surgery. In Herr’s experience with BCG treatment without maintenance therapy, 69% had tumor recurrence or progression by ten years (JCO. 155:622A(1405), 1996. In my study comparing Connaught BCG vs doxorubicin (New Engl J Med 25:1205, 1991) using 6 week induction and single maintenance instillations every 3 months for two years, complete response was seen in 70% of patients with CIS vs 34% with doxorubicin, and 48% vs 18% of patients remained disease free 5 years. �w:k>4����׬��J�Y����4ϧY�;{��y��$9]NO�����������E#��Fx+)3�7&F�RF��y�ÿ��_��2Ƅ�����5��v��a������} r���{7�`tછ�~;KeL�s���0=���y���!N�ƾ#1���98mo��7iu��&��ˑw��ӗ��}����K�q�����]F Induction BCG followed by maintenance BCG instillation after TUR, compared with induction BCG along, can reduce the risk ratios of tumor recurrence and tumor progression, and prolong RFS. Nothing is lost by postponing BCG treatment if patients have symptoms, because symptoms are evidence of continued immune stimulation. Wait three months and have cystoscope. It is available over the counter, but generally has to be ordered by the pharmacy (800-531-3333). If all clear, wait a week and begin second maintenance round of 3 weekly instillations (Month 6) Based on previous reports, one would expect that 70% or more of patients treated with chemotherapy and 77% of patients treated with surgery alone would have had recurrence. The optimal maintenance sc … In case of BCG shortage: i. 6. Contraindications to BCG Intravesical Instillation (relative/absolute) • Absolute: – reaks in the urogenital epithelium: • Traumatic catheterisation (i.e. << 1991;325:1205. Incidence and treatment We now recommend supplemental vitamins for bladder cancer patients. Do not use a filter with BCG instillation. Follow with 3 weekly instillations (reduced dose as needed) at 6, 12, 18, 24 and 36 month. malignancy other that TCC during the 8 year follow-up: 46/202 (23%) in {niftybox width=180px,float=right,textalign=left}. This specimen is collected and sent separately to pathology. A prospective randomized trial, DeHaven JI, Traynellis CT, Riggs DR, and Lamm DL: Antibiotic and Steroid, Glashan RW: A randomized controlled study of intravesical alpha-2b. In patients who have true BCG infection requiring antituberculous antibiotics, for example symptomatic prostatitis, epididymitis, or hepatitis, isoniazid plus rifampin 600mg daily should be given for 3-6 months. Wait three months and have cystoscope. If patients have moderate to severe side effects with the first or second of the three maintenance instillations, the remaining instillations in that course should be deleted. These patients can be safely treated in the office. Maintenance therapy consisted of intravesical and percutaneous BCG each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months from initiation of induction therapy. Purpose: Bacillus Calmette-Guerin (BCG) immunotherapy has been widely accepted as the optimal treatment for carcinoma in situ and high grade superficial transitional cell carcinoma. Week 2 Month 3   6  12  18  24  30 Year  3  4  5  6  8  10  12 4. Our double blind comparison of recommended daily allowance vitamins versus high doses of vitamins A, C, B6, E, and zinc (Lamm, 1994) in BCG treated patients demonstrated a remarkable and highly significant 40% further reduction in tumor recurrence. 135:265-70, 1986. Lamm DL, Meijden APM van der, Morales A, et al. Key Points • This involves having a catheter (plastic tube) passed into your bladder to instil an anti-cancer drug called BCG • BCG is a vaccine that is used against tuberculosis; it contains live 1987;5:441. Wait three months and have cystoscope. METHODS: To test the hypothesis that maintenance BCG immunotherapy might protect against the development of other malignancies as well as reduce bladder tumor recurrence, the incidence of other malignancies in patients enrolled in SWOG 8507 was recorded. Eighteen percent or more of patients will have complete response. If all clear, wait a week and begin third maintenance round of 3 weekly instillations (Month 12, or Year 1) Instruct to keep vaccination site dry for 24 h; no dressing is needed. The results of induction BCG were excellent, and very similar to our experience and that of others with BCG immunotherapy: only 52% of patients developed tumor recurrence. I have had 3 treatment periods of BCG's. BCG therapy: at all times throughout this procedure a closed system must be maintained and PPE must be worn; administer as per institutional policy; clamp (if patient unable to retain medication) or remove IDC; post instillation some clinicians recommend rotating position e.g. In the SWOG study the rate of tumor recurrence increased one year after completion of maintenance therapy. Patients with a solitary papillary tumor that appears to be low grade can be best treated with single instillation of chemotherapy (Thiotepa 30mg/30cc water for 30 minutes, for example) at the conclusion of the resection. When patients begin to have increased symptoms following BCG instillation, the dose can be reduced to 1/3, 1/10, or 1/100th as needed to prevent significant side effects with subsequent treatment. 147, 738-742, 1992. 14. 16. Wait three months and have cystoscope. Shellhammer reported 70% CR without TUR, but I prefer to resect the prostate to stage the disease and, hopefully, improve direct contact with BCG. 8. 1:119, 1995). All patients were followed for adverse effects of treatment, recurrence, disease worsening and survival. Solsona et al reported TCC in the distal ureter in 25% of 138 patients with CIS treated with cystectomy compared with 2.3% of 786 patients with superficial bladder cancer and 2.9% of 179 patients with invasive disease (Solsona, 1997). /Title (5 - Instillation BCG.pub) J Urol 147:4(242), 1992. If all clear, wait a week and begin first maintenance round of 3 weekly instillations (Month 3) BCG has been proven to be superior to chemotherapy (Thiotepa, Adriamycin, Mitomycin, and Epirubicin) in comparative controlled studies and BCG, but not chemotherapy, is found to significantly reduce disease progression. Lowe B, Sarosdy MF, Bohl RD, Weems WL, Grossman HB, Smith JA, Beck TM, ABSTRACT. Wait three months and have cystoscope. The global shortages in TICE BCG … Of 251 men, 24% developed TCC of the prostatic urethra (median 11 months), and 44% or these relapses were fatal. of complications of Bacillus Calmette-Guérin intravesical therapy in Since cultures are often negative, treatment must be given empirically. The local immune response is considered to be of primary importance in BCG immunotherapy, and up to 75% of men develop granuloma in the prostate following intravesical BCG. Wait three months and have cystoscope. Lamm DL, Sardosdy MF, Grau DA, Buchanan J, Hunt J, and DeHaven J: N Engl J Med. At the next treatment interval (eg 6 months later), instillations should be initiated with log-lower BCG dose, 1/3, 1/10, or even 1/100th CFU BCG in 50cc preservative-free saline. >>stream Urology 49:347-352, 1997. Can be reconstituted via syringe method or using closed system administration supplies. *            *   *    *    *   *     *           *, * Bladder and prostatic urethra biopsy and ureteral wash for G3 or CIS, For a simple explanation of this protocol, see below Dr. Lamm reported that three-week maintenance therapy with BCG vaccine (Calmette-Guerin bacillus) in 385 subjects increased complete response in pre-invasive bladder cancer from 70 percent to 84 percent and reduced recurrence from 52 percent to 25 percent at eight years.