Preliminary Results Show Novel Combo Appears Safe in High-Risk Non-Muscle-Invasive Bladder Cancer


Preliminary study results recently presented at the 2021 European Association of Urology Congress demonstrate that the safety profile of the combination of Bacillus Calmette-Guérin (BCG) and mitomycin is comparable to BCG alone.

Preliminary results from the phase 4 MITO-BCG study (EUDRACT) showed that consecutive treatments with Bacillus Calmette-Guérin (BCG) and the chemotherapy mytomicin resulted in a safety profile comparable to BCG alone in patients with high-risk non-muscle-invasive bladder cancer (NMIBC).1

No significant differences in safety were reported between the 2 arms. Results showed that 6 patients experienced posttreatment adverse effects (AEs) overall, with 3 reported in the combination therapy–arm. Five of the 6 AEs, which were Common Terminology Criteria for Adverse Events grade 1, comprised urethral sub-stenosis, fever, asthenia, fainting, and cystitis and did not require further treatment.

One grade 3 AE, which was acute epididymo-orchitis with abscess, was reported in the BCG-monotherapy arm and required orchiectomy. No grade 3 or higher AEs occurred in the combination arm.

“Preliminary results of our experience [in the MTIO-BCG study] support that sequential combination therapy with mytomicin and BCG is a [safe] treatment in high-risk NMIBC,” said study author Antonio Nacchia, MD, medical director of urology, Sapienza University of Rome, in a virtual presentation of the data during the meeting.

In the ongoing, open-label, phase 4 MITO-BCG study (NCT03790384), investigators are evaluating the efficacy and safety of sequential treatment with mitomycin and BCG combination therapy versus BCG alone in patients with high-risk NMIBC. The protocol had been approved by the Italian Medicines Agency in August 2018 and then by the Ethical Committee in Italy in December 2018; the protocol started in March 2019.

To be eligible for enrollment, patients must have high-risk NMIBC that was either: T1, grade 3, carcinoma in situ, multiple and recurrent large Ta, G1G2, or were in the last EAU recurrence category of EAU/EORTC recurrence score ≥10. Patients need to be between 40 and 75 years of age.

Those with low-risk NMIBC, muscle-invasive bladder cancer, concomitant urothelial bladder cancer in the upper-urinary tract, had prior bladder or prostate surgery, prior prostate or bladder radiotherapy, urinary tract infection, chronic urinary retention or indwelling catheters, have neurologic issues, had prior BCG infections, prior or current chemotherapy for other malignancies, or residual tumor on re-transurethral resection of the bladder were excluded from enrollment.2 Additionally, patients could have a World Health Organization performance status between 3 and 4.

Thirty-six patients were randomized to receive standard BCG induction therapy as an instillation once weekly for 6 weeks with an 81-mg Connaught strain of BCG (n = 21) or the BCG protocol with 40 mg of mitomycin instillation given the day before BCG starts at once weekly for 6 weeks (n = 15). Cystoscopy and urine cytology were both conducted every 3 months along with annual CT scans. The median age of patients was 67 years.

The primary end point of the trial is recurrence rate, with overall toxicity being a secondary end point. Assessments of health-related quality of life serves as an exploratory end point.

Trial enrollment will continue until 200 patients are included on the study, Nacchia concluded.

In April 2020, the FDA approved mitomycin gel (UGN-101; Jelmyto) as the first therapy to treat patients with low-grade upper tract urothelial cancer. Mitomycin gel uses the RTGel™ technology platform and is designed to permit longer exposure of mitomycin to urinary tract tissue, which allows for the nonsurgical treatment of these tumors. The therapy is administered to patients using standard ureteral catheters.


  1. De Nunzio C, Nacchia A, Lombardo R, et al. Safety evaluation of sequential Mitomycin and Bacillus Calmette-Guérin treatment versus Bacillus Calmette-Guérin monotherapy in patients with high risk non-muscle invasive bladder cancer: MITOBCG study (EUDRACT Number 2017-004540-37) preliminary results.Presented at: 36th Annual European Association of Urology Congress; July 8-12, 2021; virtual. Abstract P0447.
  2. Sequential combination therapy in bladder cancer (MITOBCG). Updated December 31, 2018. Accessed July 10, 2020.

This article was originally published on OncLive as “Sequential Mitomycin/BCG Combo Shows Preliminary Safety in High-Risk NMIBC”

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