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Gene therapy shows promise for bladder cancer subtype
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Recombinant adenovirus interferon alfa with Syn3 appeared well tolerated and showed promising efficacy among patients with high-grade nonmuscle-invasive bladder cancer, according to results of a phase 2 clinical trial.
Recombinant adenovirus interferon alfa with Syn3 (Instiladrin, FKD Finland) is a replication-deficient recombinant adenovirus gene transfer vector.
“The data, which are consistent with a previous phase 1 clinical trial, found threefold improvement in RFS with Instiladrin compared with valrubicin [Valstar, Endo Pharmaceuticals], the only agent currently approved for this indication,” Colin P.N. Dinney, MD, urologist at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “We are encouraged by these data and the promise it may bring to improving outcomes for this group of patients.”
Bacillus Calmette-Guerin (BCG) vaccine is the preferred treatment for these patients, but 30% will not respond to this therapy and more than 50% will experience recurrence and progression.
Effective therapies for BCG-unresponsive nonmuscle-invasive bladder cancer are needed to avoid bladder removal surgery and to improve disease-specific outcomes. However, recombinant adenovirus interferon alfa with Syn3 may present another option.
“Recombinant adenovirus interferon alfa gene therapy is a breakthrough opportunity ... because it is formulated to allow the adenovirus to penetrate the cells that line the bladder,” Dinney said. “Once in the cells, the gene it contains causes expression of the therapeutic interferon protein in both normal and cancerous urothelial cells of the patient for up to 3 weeks. So, when the cancerous cells are killed rapidly by the treatment, the healthy cells continue to produce the interferon, providing sustained treatment.”
Researchers randomly assigned 43 patients with high-grade BCG refractory or relapsed nonmuscle-invasive bladder cancer to 1 x 1011 viral particles/mL (n = 22) or 3 x 1011 viral particles/mL (n = 21) recombinant adenovirus interferon alfa with Syn3 between November 2012 and April 2015.
Patients who responded to treatment at 3, 6 and 9 months underwent retreatment at 4, 7 and 10 months.
One-year high-grade RFS served as the primary endpoint.
Forty patients received at least one dose.
Researchers reported rates of 1-year high-grade RFS of 33.3% (90% CI, 22.6-49.2) among patients in the low-dose group and 36.5% (90% CI, 18.8-58.2) in the high-dose group.
Fourteen patients (90% CI, 22.6-49.2) remained recurrence free 1 year after initial treatment. Of these, two experienced recurrence at 21 months and 28 months after the start of therapy, and one died of an upper tract tumor at 17 months without a recurrence.
The median time to recurrence or death was 6.5 months (90% CI, 3.52-12.78) — 3.52 months for the low-dose group and 11.73 months for the high-dose group.
The most common treatment-related adverse events included micturition urgency (n = 16), dysuria (n = 16), fatigue (n = 13), pollakiuria (n = 11), hematuria (n = 10) and nocturia (n = 10). Researchers observed no grade 4 or grade 5 adverse events. None of the patients discontinued treatment due to an adverse event.
A phase 3 clinical trial of high-dose recombinant adenovirus interferon alfa with Syn3 is ongoing.
“As we make inroads to treat bladder cancer, we appreciate the support of oncologists and urologists to enroll patients in clinical trials,” Dinney said. – by Melinda Stevens
For more information:
Colin P.N. Dinney, MD, can be reached at cdinney@mdanderson.org.
Disclosures: Dinney reports financial relationships with FKD Therapies Oy and University of Michigan Comprehensive Center. Please see the full study for a list of all other authors’ relevant financial disclosures.
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