Abstract
Purpose: The quinone based bioreductive drug apaziquone (EO9) failed to demonstrate efficacy in previous phase II studies following intravenous administration. We determined the dose of apaziquone that can be safely administered intravesically and explored its activity for superficial bladder transitional cell carcinoma.
Materials and Methods: Six patients with multifocal, Ta/T1 and G1/G2 transitional cell carcinoma of the bladder received escalating doses of apaziquone formulated as EOquin™ (0.5 mg/40 ml up to 16 mg/40 ml) weekly for 6 weeks. A further 6 patients received weekly apaziquone at the highest nontoxic dose established. Pharmacokinetic parameters were determined in urine and blood, and the pharmacodynamic markers NQO1 (reduced nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase-1) and glucose transporter 1 were also characterized. Efficacy was determined against a marker lesion.
Results: Local toxicity (grades 2 and 3 dysuria, and hematuria) was observed at doses of 8 mg/40 ml and above but 4 mg/40 ml was well tolerated with no systemic or local side effects. Apaziquone in urine increased linearly with the dose but no apaziquone was detected in plasma. In 8 of 12 patients complete macroscopic and histological disappearance of the marker lesion occurred. A correlation between response and NQO1 and/or glucose transporter 1 expression could not be established.
Conclusions: Intravesical administration of 4 mg/40 ml apaziquone was well tolerated and had ablative activity against superficial bladder cancer marker lesions.
| Language | English |
|---|---|
| Pages | 1344-1348 |
| Number of pages | 5 |
| Journal | Journal of Urology |
| Volume | 176 |
| Issue number | 4 |
| Early online date | 3 Sep 2006 |
| DOIs | |
| Publication status | Published - Oct 2006 |
| Externally published | Yes |
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Phase I/II Pilot Study of Intravesical Apaziquone (EO9) for Superficial Bladder Cancer. / Puri, Rajiv; Palit, Victor; Loadman, Paul M.; Flannigan, Michael; Shah, Tariq; Choudry, Guzanfar A.; Basu, Saurajyoti; Double, John A.; Lenaz, Gino; Chawla, Shanta; Beer, Mario; Van Kalken, Coen; de Boer, Richard; Beijnen, Jos H.; Twelves, Christopher J.; Phillips, Roger M.
In: Journal of Urology, Vol. 176, No. 4, 10.2006, p. 1344-1348.Research output: Contribution to journal › Article
TY - JOUR
T1 - Phase I/II Pilot Study of Intravesical Apaziquone (EO9) for Superficial Bladder Cancer
AU - Puri, Rajiv
AU - Palit, Victor
AU - Loadman, Paul M.
AU - Flannigan, Michael
AU - Shah, Tariq
AU - Choudry, Guzanfar A.
AU - Basu, Saurajyoti
AU - Double, John A.
AU - Lenaz, Gino
AU - Chawla, Shanta
AU - Beer, Mario
AU - Van Kalken, Coen
AU - de Boer, Richard
AU - Beijnen, Jos H.
AU - Twelves, Christopher J.
AU - Phillips, Roger M.
PY - 2006/10
Y1 - 2006/10
N2 - Purpose: The quinone based bioreductive drug apaziquone (EO9) failed to demonstrate efficacy in previous phase II studies following intravenous administration. We determined the dose of apaziquone that can be safely administered intravesically and explored its activity for superficial bladder transitional cell carcinoma. Materials and Methods: Six patients with multifocal, Ta/T1 and G1/G2 transitional cell carcinoma of the bladder received escalating doses of apaziquone formulated as EOquin™ (0.5 mg/40 ml up to 16 mg/40 ml) weekly for 6 weeks. A further 6 patients received weekly apaziquone at the highest nontoxic dose established. Pharmacokinetic parameters were determined in urine and blood, and the pharmacodynamic markers NQO1 (reduced nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase-1) and glucose transporter 1 were also characterized. Efficacy was determined against a marker lesion. Results: Local toxicity (grades 2 and 3 dysuria, and hematuria) was observed at doses of 8 mg/40 ml and above but 4 mg/40 ml was well tolerated with no systemic or local side effects. Apaziquone in urine increased linearly with the dose but no apaziquone was detected in plasma. In 8 of 12 patients complete macroscopic and histological disappearance of the marker lesion occurred. A correlation between response and NQO1 and/or glucose transporter 1 expression could not be established. Conclusions: Intravesical administration of 4 mg/40 ml apaziquone was well tolerated and had ablative activity against superficial bladder cancer marker lesions.
AB - Purpose: The quinone based bioreductive drug apaziquone (EO9) failed to demonstrate efficacy in previous phase II studies following intravenous administration. We determined the dose of apaziquone that can be safely administered intravesically and explored its activity for superficial bladder transitional cell carcinoma. Materials and Methods: Six patients with multifocal, Ta/T1 and G1/G2 transitional cell carcinoma of the bladder received escalating doses of apaziquone formulated as EOquin™ (0.5 mg/40 ml up to 16 mg/40 ml) weekly for 6 weeks. A further 6 patients received weekly apaziquone at the highest nontoxic dose established. Pharmacokinetic parameters were determined in urine and blood, and the pharmacodynamic markers NQO1 (reduced nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase-1) and glucose transporter 1 were also characterized. Efficacy was determined against a marker lesion. Results: Local toxicity (grades 2 and 3 dysuria, and hematuria) was observed at doses of 8 mg/40 ml and above but 4 mg/40 ml was well tolerated with no systemic or local side effects. Apaziquone in urine increased linearly with the dose but no apaziquone was detected in plasma. In 8 of 12 patients complete macroscopic and histological disappearance of the marker lesion occurred. A correlation between response and NQO1 and/or glucose transporter 1 expression could not be established. Conclusions: Intravesical administration of 4 mg/40 ml apaziquone was well tolerated and had ablative activity against superficial bladder cancer marker lesions.
KW - bladder
KW - bladder neoplasms
KW - carcinoma
KW - EO9
KW - transitional cell
UR - http://www.scopus.com/inward/record.url?scp=33748094636&partnerID=8YFLogxK
UR - http://www.sciencedirect.com/journal/the-journal-of-urology
U2 - 10.1016/j.juro.2006.06.047
DO - 10.1016/j.juro.2006.06.047
M3 - Article
VL - 176
SP - 1344
EP - 1348
JO - Journal of Urology
T2 - Journal of Urology
JF - Journal of Urology
SN - 0022-5347
IS - 4
ER -