Local treatment with large surface area microparticle docetaxel (LSAM-DTX) may improve the health of patients with high-risk nonmuscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT), according to investigators.
After TURBT, 19 patients received direct injection LSAM-DTX into the resection site and intravesical LSAM-DTX, followed by 6-week induction and 3-week maintenance courses. Investigators administered LSAM-DTX using a 3+3 dose escalation strategy. Of the 19 patients, 14 had prior bacillus Calmette-Guérin (BCG) exposure and 16 had prior TURBT.
Median recurrence-free survival was 5.4 months in the 3 lowest dose escalation groups and 12.2 months in the high-dose and expansion groups, Gere S. diZerega, MD, president of US Biotest, Inc. in San Luis Obispo, California, and colleagues reported in The Journal of Urology. The risk for recurrence was a significant 71% lower for the high-dose and expansion groups vs low-dose groups.
“Preliminary efficacy data suggest post-TURBT direct injection and intravesical therapy of high dose LSAM-DTX may provide therapeutic benefits to patients with high-risk NMIBC,” the investigators concluded.
No serious adverse events occurred. Among 31 local treatment emergent adverse events, hematuria, dysuria, and urinary tract infections were the most common.
Bladder biopsies from 2 BCG-naive patients without prior TURBT showed local immune cell infiltration and increased expression of PD-1, PD-L1, and CTLA-4 — checkpoint inhibitor targets.
In an accompanying editorial, Johanna M. Schafer, PhD, and Debasish Sundi, MD, of The Ohio State University Wexner Medical Center in Columbus, Ohio, commented:
“LSAM-DTX does appear to have some efficacy as a high-dose monotherapy. These results provide an impetus for additional preclinical research to evaluate combining LSAM-DTX with immune checkpoint blockade. The authors should be commended for their efforts, which may help to expand treatment choices for patients with NMIBC.”
In a separate editorial comment, Alex Sankin, MD, of Montefiore Medical Center and Albert Einstein College of Medicine in Bronx, New York, called urothelial carcinoma “the uninvited garden weed of the bladder. It is a parasite that consumes the nutrients of its host and tends to recur when its roots are not eliminated during transurethral resection. Similar to applying garden herbicide, local injection of chemotherapy directly into the resection bed may destroy tumor remnants and has the advantages of reducing systemic toxicity (compared to intravenous administration), increasing exposure time to target tissue, and promoting infiltration of antitumor immune cells.”
Disclosure: This research was supported by NanOlogy, LLC. Please see the original reference for a full list of disclosures.
Kates M, Mansour AM, Lamm DL, et al. Phase 1/2 trial results of a large surface area microparticle docetaxel for the treatment of high-risk nonmuscle-invasive bladder cancer. J Urol. 2022 Oct;208(4):821-829. doi:10.1097/JU.0000000000002778