"The U.S. Food and Drug Administration today expanded the approved uses of Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound) to treat patients with late-stage (metastatic) pancreatic cancer.
Symptoms of bladder irritability, related to the inflammatory response induced, are reported in approximately 60% of patients receiving TICE® BCG. The symptoms typically begin 4–6 hours after instillation and last 24–72 hours. The irritative side effects are usually seen following the third instillation, and tend to increase in severity after each administration.
The irritative bladder adverse effects can usually be managed symptomatically with products such as pyridium, propantheline bromide, oxybutynin chloride and acetaminophen. The mechanism of action of the irritative side effects has not been firmly established, but is most consistent with an immunological mechanism.3 There is no evidence that dose reduction or antituberculous drug therapy can prevent or lessen the irritative toxicity of TICE® BCG.
“Flu-like” symptoms (malaise, fever, and chills) which may accompany the localized, irritative toxicities often reflect hypersensitivity reactions which can be treated symptomatically. Antihistamines have also been used.5
Adverse reactions to TICE® BCG tend to be progressive in frequency and severity with subsequent instillation. Delay or postponement of subsequent treatment may or may not reduce the severity of a reaction during subsequent instillation.
Although uncommon, serious infectious complications of intravesical BCG have been reported.2,3,6 The most serious infectious complication of BCG is disseminated sepsis with associated mortality. In addition, M. bovis infections have been reported in lung, liver, bone, bone marrow, kidney, regional lymph nodes, and prostate in patients who have received intravesical BCG. Some male genitourinary tract infections (orchitis/epididymitis) have been resistant to multiple drug antituberculous therapy and required orchiectomy.
If a patient develops persistent fever or experiences an acute febrile illness consistent with BCG infection, BCG treatment should be discontinued and the patient immediately evaluated and treated for systemic infection (see WARNINGS).
TABLE V: SUMMARY OF ADVERSE EFFECTS SEEN IN 674
PATIENTS WITH SUPERFICIAL BLADDER CANCER, INCLUDING 153 WITH CARCINOMA IN SITU
|Adverse Event||N||Overall (Grade ≥ 3)||Adverse Event||N||Overall (Grade ≥ 3)|
|Dysuria||401||60% (11%)||Arthritis/Myalgia||18||3% ( < 1%)|
|Urinary Frequency||272||40% (7%)||Headache/Dizziness||16||2% (0)|
|Flu-Like Syndrome||224||33% (9%)||Urinary Incontinence||16||2% (0)|
|Hematuria||175||26% (7%)||Anorexia/Weight Loss||15||2% ( < 1%)|
|Fever||134||20% (8%)||Urinary Debris||15||2% ( < 1%)|
|Malaise/Fatigue||50||7% (0)||Allergy||14||2% ( < 1%)|
|Cystitis||40||6% (2%)||Cardiac (Unclassified)||13||2% (1%)|
|Urgency||39||6% (1%)||Genital Inflammation/Abscess||12||2% ( < 1%)|
|Cramps/Pain||27||4% (1%)||Respiratory (Unclassified)||11||2% ( < 1%)|
|Rigors||22||3% (1%)||Urinary Tract Infection||10||2% (1%)|
|Nausea/Vomiting||20||3% ( < 1%)||Abdominal Pain||10||2% (1%)|
The following adverse events were reported in ≤ 1% of patients: anemia, BCG sepsis, coagulopathy, contracted bladder, diarrhea, epididymitis/prostatitis, hepatic granuloma, hepatitis, leukopenia, neurologic (unclassified), orchitis, pneumonitis, pyuria, rash, thrombocytopenia, urethritis, and urinary obstruction.
In SWOG study 8795, toxicity evaluations were available on a total of 222 TICE® BCG-treated patients and 220 MMC-treated patients. Direct bladder toxicity (cramps, dysuria, frequency, urgency, hematuria, hemorrhagic cystitis, or incontinence) was seen more often with TICE® BCG, with 356 events compared to 234 events for MMC. Grade ≤ 2 toxicity was seen significantly more frequently following TICE® BCG treatment (p=0.003). No life-threatening toxicity was seen in either arm. Systemic toxicity with TICE® BCG was markedly increased compared to that of MMC, with 181 events for TICE® BCG compared to 80 for MMC. The frequency of toxicity was increased in all grades, particularly for grades 2 and 3. The most common complaints were malaise, fatigue and lethargy, fever, and abdominal pain. Thirty-two TICE® BCG patients were reported to have been treated with isoniazid. Five TICE® BCG patients had liver enzyme elevation, including two with grade 3 elevations. Eighteen of the 222 (8.1%) TICE® BCG patients failed to complete the prescribed protocol compared to 6.2% in the MMC group. Table VI summarizes the most common adverse reactions reported in this trial.7
TABLE VI: MOST COMMON ADVERSE REACTIONS IN SWOG STUDY
(N = 222)
(N = 220)
|All Grades||Grade ≥ 3||All Grades||Grade ≥ 3|
|Dysuria||115 (52%)||6 (3%)||77 (35%)||5 (2%)|
|Urgency/Frequency||112 (50%)||5 (2%)||63 (29%)||7 (3%)|
|Hematuria||85 (38%)||6 (3%)||56 (25%)||5 (2%)|
|Flu-Like Symptoms||54 (24%)||1 ( < 1%)||29 (13%)||0|
|Fever||37 (17%)||1 ( < 1%)||7 (3%)||0|
|Pain (Not Specified)||37 (17%)||4 (2%)||22 (10%)||1 ( < 1%)|
|Hemorrhagic Cystitis||19 (9%)||3 (1%)||10 (5%)||0|
|Chills||19 (9%)||0||2 (1%)||0|
|Bladder Cramps||18 (8%)||0||9 (4%)||0|
|Nausea||16 (7%)||0||12 (5%)||0|
|Incontinence||8 (4%)||0||3 (1%)||0|
|Diaphoresis||7 (3%)||0||1 ( < 1%)||0|
|Rash||6 (3%)||1 ( < 1%)||16 (7%)||2 (1%)|
|*The adverse reaction profile of TICE® BCG was similar in the Nijmegen study.8|
Read the Tice (bacillus of calmette and guerin) Side Effects Center for a complete guide to possible side effects
Drug combinations containing 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 TICE® BCG. Antimicrobial therapy for other infections may interfere with the effectiveness of TICE® BCG. There are no data to suggest that the acute, local urinary tract toxicity common with BCG is due to mycobacterial infection and antituberculosis drugs (e.g., isoniazid) should not be used to prevent or treat the local, irritative toxicities of TICE® BCG.
2. Rawls WH, Lamm DL, Lowe BA, Crawford ED, Sarosdy MF, Montie JE, Grossman HB, Scardino PT. Fatal Sepsis Following Intravesical Bacillus Calmette-Guerin Administration For Bladder Cancer. J Urol 1990;144:1328-1330.
3. Lamm DL, van der Meijden APM, Morales A, Brosman SA, Catalona WJ, Herr HW, et al. Incidence and Treatment of Complications of Bacillus Calmette-Guerin Intravesical Therapy in Superficial Bladder Cancer. J. Urol 1992; 147: 596-600.
4. Stone MM, Vannier AM, Storch SK, Nitta AT, Zhang Y. Brief Report: Meningitis Due to Iatrogenic BCG Infection in Two Immunocompromised Children. NEJM 1995: 333:561-563.
5. Steg A, Leleu C, Debre B, Gibod-Boccon L, Sicard D. Systemic Bacillus Calmette-Guerin Infection in Patients Treated by Intravesical BCG Therapy for Superficial Bladder Cancer. EORTC Genitourinary Group Monograph 6: BCG in Superficial Bladder Cancer. Edited by F.M. J. Debruyne, L. Denis and A.P.M. van der Meijden. New York: Alan R. Liss Inc., pp. 325-334.
6. van der Meijden, APM. Practical Approaches to the Prevention and Treatment of Adverse Reactions to BCG. Eur Urol 1995;27(suppl 1):23-28.
7. Lamm DL, Blumenstein BA, Crawford ED, Crissman JD, Lowe BA, Smith JA, Sarosdy MF, Schellhammer PF, Sagalowsky AI, Messing EM, et al. Randomized Intergroup Comparison of Bacillus Calmette-Guerin Immunotherapy and Mitomycin C Chemotherapy Prophylaxis in Superficial Transitional Cell Carcinoma of the Bladder. Urol Oncol 1995; 1:119-126.
8. Witjes JA, van der Meijden APM, Witjes WPJ, et al. A Randomized Prospective Study Comparing Intravesical Instillations of Mitomycin-C, BCG-Tice, and BCG-RIVM in pTa-pT1 Tumours and Primary Carcinoma In Situ of the Urinary Bladder. Eur J Cancer 1993;29A(12):1672-1676.
Last reviewed on RxList: 8/18/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Tice Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options.