Some patients with RCC are unsuitable for nephrectomy. SIRT is used for unresectable liver cancers, and has properties that make it potentially useful for primary RCC. RESIRT is the first-in-human study to evaluate safety and feasibility of SIRT for primary RCC.
Pts not amenable for or who declined conventional therapy were eligible; metastases were permitted. A single transfemoral microcatheter administration of Y-90 resin microspheres (SIR-Spheres; Sirtex, Australia) was delivered superselectively via the renal artery to the tumour at intended radiation doses of 75, 100, 150, 200, 300 Gy and a final cohort with a procedural endpoint of imminent stasis, in a dose-escalation design. Post-SIRT follow-up was 12 months. The primary endpoint was safety and toxicity at 30 days post-SIRT. Secondary endpoints included tumour response (RECIST v1.1).
The study enrolled 21 pts with RCC, mean age 74.9 years and WHO performance status of 0 (81%) or 1 (19%). Six (29%) pts had metastatic RCC, 7 (33%) had previously undergone total nephrectomy of the contralateral kidney, 1 (5%) received prior chemotherapy, 1 (5%) progressed after cryotherapy to the target organ and 3 (14%) received other prior therapy. Median follow-up was 11.9 months (95% CI 11.8–12.0). The intended doses were delivered without any dose-limiting toxicity. 15/21 (71%) pts experienced 44 AEs within 30 days post-SIRT. Eight (38%) pts had AEs grade ≥3, all unrelated to SIRT; 8 pts (38%) had 12 AEs that were related to SIRT (all grade 1–2, no SAEs), of which 1 occurred pre SIRT. Treatment-related AEs were fatigue/tiredness, pain, hypertension, lack of appetite, ‘heaviness’, bruised groin and hypomagnesemia. 15 SAEs were reported in 8 (38%) pts; 2 within 30 days post-SIRT (shortness of breath, prolonged hospitalisation). Best overall tumour responses were partial response 1/19 (5.3%), stable disease 17/19 (89.5%) and progressive disease 1/19 (5.3%).
This pilot study demonstrates good tolerability of SIRT at all dose levels including imminent stasis in treating primary tumours in RCC pts otherwise unsuitable for conventional therapy.
Clinical trial identification
Australian New Zealand Trials Registry: Trial ID ACTRN12610000690055
Legal entity responsible for the study
Sirtex Technology Pty Ltd.
Sirtex Medical Limited
P. de Souza: Australian Advisory Boards until 2014, nil afterwards: GSK, Pfizer, Janssen, Astellas. D. Cade: Full time employee of Sirtex Medical Limited Receives salary from Sirtex Medical Limited S.J. de Silva: Proctor for Sirtex (unpaid). All other authors have declared no conflicts of interest.