Intravesical recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3; Instiladrin) as treatment for high-grade non-muscle-invasive bladder cancer (NMIBC) patients who are unresponsive to bacillus Calmette-Guerin (BCG) demonstrated acceptable toxicity and a clinically meaningful durable response that has been maintained beyond 36 months in some patients when investigated in a phase II study.
The abstract reporting on the results of the open-label, multicenter trial was published online in the Journal of Clinical Oncology (Aug. 23, 2017). The study randomized patients equally into two groups to receive intravesical rAd-IFNα/Syn3 1 × 1011 viral particles (vp)/mL or 3 × 1011 vp/mL. Patients judged to have been cancer free at follow-up visits conducted at months 3, 6, and 9 were retreated at months 4, 7, and 10.
Results of the primary endpoint analysis showed that at 12 months, 14 (35%) of 40 treated patients were high-grade recurrence-free. The response rate was comparable in the two dose groups. In comparison, valrubicin (Valstar), the only treatment approved by the FDA for BCG-refractory disease, has been associated with a 12-month complete response rate of only 8% to 10%.
No patients in the phase II study developed a Grade 4 or 5 adverse event or discontinued treatment because of a drug-related adverse event. There were 10 Grade 3 adverse events that were considered to be serious, but of these, only one episode of diarrhea and one episode of acute renal failure secondary to a urinary tract infection were judged related to the study drug, and both issues resolved with medical therapy.
Urgency and frequency of micturition were the most common adverse events (40%), but they were generally minor, transient, and could be minimized by pretreatment with anticholinergics.