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Biological response modifiers for the treatment of superficial bladder tumors
1Department of Urology, Erasme Hospital, University Clinics of Brussels, Belgium. azloota@ulb.ac.be
Background:
For more than 20 years, superficial bladder tumors have been demonstrated to be sensitive to several biological response modifiers and especially to immunomodulators. The best-known and studied immunomodulator is the bacillus Calmette-Guérin (BCG). However, despite its well-recognized efficacy, BCG is not a universal panacea and is associated with potentially significant side effects.
Methods:
New perspectives in BCG therapy aiming to increase BCG efficacy or to decrease side effects include the use of genetically engineered BCG strains producing cytokines as well as the use of purified BCG subcomponents. Because a cascade of immunological reactions including the secretion of several cytokines has been demonstrated in the BCG mode of action, many other biological response modifiers and especially immunomodulators have been studied for superficial transitional cell carcinoma therapy. Some were investigated in human trials, others are still in laboratory studies; some are administered intravesically whereas others are given orally. Interferon-alpha (IFN-alpha) intravesical instillations have been evaluated in several controlled studies.
Results:
Although toxicity of intravesical IFN is minimal, its optimal dose, schedule and efficacy remain to be defined. Recent prospective studies comparing IFN to BCG intravesical therapy have been somewhat disappointing although this cytokine may be effective in some patients with T(a)-T(1) disease who have failed BCG therapy. Other immunomodulators administered intravesically investigated in clinical studies include interleukin 2 (recently used in a clinical study with a marker tumor response), levamisole, Rubratin, a Nocardia rubra cell wall skeleton, and keyhole limpet hemocyanin. Several biological response modifiers administered orally such as vitamin A (and its derivatives), Lactobacillus casei or bropirimine have been tested in clinical trials as well. In contrast, Allium sativum (garlic) or OK-432 (a streptococcal preparation) or BCG subfractions have been tested in laboratory studies only.
Conclusions:
Published reports on several of these biological response modifiers suggest that these compounds may be an alternative in patients with superficial bladder cancer who have failed or have not tolerated BCG, but further evaluation to improve efficacy, durability and understand their mechanism of action is warranted.
Insights
New immunomodulators show promise for superficial bladder cancer treatment when bacillus Calmette-Guérin (BCG) therapy fails or causes side effects. Further research is needed to optimize efficacy and durability.
Area of Science:
- Oncology
- Immunology
- Urology
Background:
- Superficial bladder tumors are sensitive to immunomodulators like bacillus Calmette-Guérin (BCG).
- BCG is effective but has limitations, including potential side effects and lack of universal efficacy.
- Research is exploring alternatives to enhance BCG therapy or mitigate its adverse effects.
Purpose of the Study:
- To review biological response modifiers (BRMs) and immunomodulators for superficial transitional cell carcinoma (TCC).
- To assess the efficacy and potential of alternative treatments for patients unresponsive or intolerant to BCG therapy.
Main Methods:
- Review of published studies on various BRMs and immunomodulators.
- Analysis of agents administered intravesically (e.g., Interferon-alpha, Interleukin-2) and orally (e.g., vitamin A, bropirimine).
- Inclusion of agents tested in human trials and laboratory studies.
Main Results:
- Intravesical Interferon-alpha (IFN-alpha) shows minimal toxicity, but optimal use is undefined; it may benefit BCG-refractory patients.
- Other intravesical agents like Interleukin-2 and Nocardia rubra cell wall skeleton have been investigated.
- Oral agents including vitamin A derivatives and bropirimine have undergone clinical trials.
Conclusions:
- Several BRMs and immunomodulators may offer alternatives for superficial bladder cancer patients with BCG failure or intolerance.
- Further research is essential to improve the efficacy, durability, and understanding of the mechanisms of action for these alternative therapies.