Vascular-targeted photodynamic therapy (VTP) with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma (UTUC). This phase I trial (NCT03617003) evaluated the safety of VTP with WST-11 in UTUC.
Nineteen patients underwent up to 2 endoscopic VTP treatments, with follow-up for up to 6 months. Patients who had residual or recurrent UTUC (any grade/size) failing prior endoscopic treatment or were unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose (MTD) of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days post-treatment.
Fourteen (74%) patients received the MTD of 200mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up.
VTP with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for UTUC. The recently initiated multi-center phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.
The Journal of urology. 2023 Feb 01 [Epub ahead of print]
Wesley Yip, Daniel D Sjoberg, Lucas M Nogueira, Andrew T Tracey, Ricardo G Alvim, Peter A Reisz, Quinlan Demac, Nicole E Benfante, Rand W Vanden Berg, Kwanghee Kim, Hikmat Al-Ahmadie, Oscar Lin, Bernard H Bochner, Guido Dalbagni, S Machele Donat, Eugene J Pietzak, A Ari Hakimi, David B Solit, Avigdor Scherz, Dean F Bajorin, Jonathan A Coleman
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York., Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Weizmann Institute of Science, Rehovot, Israel.