Two-year follow-up of the phase II marker lesion study of intravesical apaziquone for patients with non-muscle invasive bladder cancer

Department of Urology, Radboud University Nijmegen Medical Centre, Inter Mail 659, PO Box 9101, Nijmegen 6500 HB, The Netherlands.
World Journal of Urology (Impact Factor: 2.67). 03/2009; 27(3):337-42. DOI: 10.1007/s00345-009-0382-4
Source: PubMed


To study the time-to-recurrence and duration of response in non-muscle invasive bladder cancer (NMIBC) patients, with a complete ablative response after intravesical apaziquone instillations.
Transurethral resection of bladder tumour(s) (TURBT) was performed in patients with multiple pTa-T1 G1-2 urothelial cell carcinoma (UCC) of the bladder, with the exception of one marker lesion of 0.5-1.0 cm. Intravesical apaziquone was administered at weekly intervals for six consecutive weeks, without maintenance instillations. A histological confirmed response was obtained 2-4 weeks after the last instillation. Routine follow-up (FU) was carried out at 6, 9, 12, 18 and 24 months from the first apaziquone instillation.
At 3 months FU 31 of 46 patients (67.4%) had a complete response (CR) to ablative treatment. Side-effects on the long-term were only mild. Two CR patients dropped out during FU. On intention-to-treat (ITT) analysis 49.5% of the CR patients were recurrence-free at 24 months FU, with a median duration of response of 18 months. Of 15 no response (NR) patients, only two received additional prophylactic instillations after TURBT. On ITT-analysis 26.7% of the NR patients were recurrence-free (log rank test, P = 0.155). The overall recurrence-free survival was 39% (18 of 46 patients) at 24 months FU.
The CR of the marker lesion in 67% of patients was followed by a recurrence-free rate of 56.5% at 1-year FU, and 49.5% at 2-year FU. These long-term results are good in comparison with the results of other ablative studies.

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    • "Bioreductive prodrugs, which are activated in hypoxic environments, have been evaluated as potential anti-cancer agents to selectively kill hypoxic tumor cells. For instance, apaziquone (EO9), a bioreductive prodrug, was used through instillation to treat bladder cancer and significantly reduced the rate of tumor recurrence in the clinical trials (Hendricksen et al., 2009; Jain et al., 2009). "

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