Mitomycin C from Birth to Adulthood

Abstract

Mitomycin C (MMC) intravesical therapy for "superficial" papillary bladder tumors was firstly introduced in the early seventies with promising results. In the following years, several pharmacokinetic studies investigated its mechanism of action to optimize the intravesical administration. Numerous studies confirmed thereafter both the ablative and the prophylactic efficacy and the low toxicity of MMC when intravesically given. In 1984, a complete response rate of 42% in 60 patients not responsive to thiotepa was reported with intravesical MMC at the dose of 40 mg diluted in 40 ml for 8 weeks. In the following decades, many large randomized studies showed the benefit of intravesical prophylaxis with MMC versus transurethral resection (TUR) alone. Since 2002, the role of adjuvant intravesical chemotherapy and of an early MMC instillation in preventing recurrence compared with TUR alone has been confirmed by large meta-analyses and stated by the European Association of Urology (EAU) guidelines. The need for further intravesical chemotherapy after the early instillation in patients at intermediate-high risk of recurrence has been proved by several trials. Although intravesical Bacillus Calmette-Guerìn (BCG) is considered the best choice for high-risk patients and MMC for the low-risk group, both MMC and BCG can be given to prevent recurrence in intermediate-risk patients. However, the higher efficacy of BCG over MMC is evident only if maintenance regimen is administered. Despite its proven efficacy, immediate intravesical MMC is not yet fully entered in common clinical practice and efforts should be made by the urologists to optimize its adoption.

Clinical Efficacy of Neoadjuvant Intravesical Mitomycin-C Therapy Immediately Before Transurethral Resection of Bladder Tumor in Patients With Nonmuscle-invasive Bladder Cancer: Preliminary Results of a Prospective, Randomized Phase II Study

“…11-14 A single immediate IMMC after TURBT is seldom used in case of an extended, deep resection, or suspected bladder perforation because iatrogenic bladder perforation, extravasation of MMC into the subperitoneal or intraperitoneal space, and perivesical fat necrosis require surgical debridement, cystectomy, and/or intensive care admission. 11-14…”

“…[11][12][13][14] A single immediate IMMC after TURBT is seldom used in case of an extended, deep resection, or suspected bladder perforation because iatrogenic bladder perforation, extravasation of MMC into the subperitoneal or intraperitoneal space, and perivesical fat necrosis require surgical debridement, cystectomy, and/or intensive care admission. [11][12][13][14] The optimal IMMC schedule, such as instillation intervals and numbers in neoadjuvant regimens for reducing the recurrence of NMIBC, have yet to be defined. A single immediate IMMC before TURBT may be suboptimal in inhibiting tumor cell replication and blocking tumor regrowth.…”

Thermal Intravesical Chemotherapy Reduce Recurrence Rate for Non-muscle Invasive Bladder Cancer Patients: A Meta-Analysis

“…MMC and THP are the main drugs applied in studies. MMC is an anti-metabolite drug identified from the products of a species of Streptomyces caespitosus (32). It destroys the structure and function of DNA, inhibits the replication of DNA, and kills tumor cells both in the proliferating and resting phase.…”

Advances in Diagnosis and Therapy for Bladder Cancer

“…Mitomycin C (MMC) and bacillus calmette-guérin (BCG) are common agents for NMIBC perioperative treatment. However, the clinical application of MMC is limited by toxicity and cumulative myelosuppression after systematic administration [2,85]. The response rate of BCG induction was 50% for patients with CIS, resulting in most patients receiving additional maintenance therapy [86].…”