Here's the abstract:
C185 Phase I clinical evaluation of intravesical eoquin (EO9) against superficial bladder cancer: Preliminary results.
Rajiv Puri, Saurajyoti Basu, Paul Loadman, Sandra W. Martin, Victor Palit, Gino Lenaz, Coen Van Kalken, Brian Naylor, and Roger M. Phillips. Department of Urology, St Lukes Hospital, Bradford, United Kingdom, Tom Connors Cancer Research Centre, Bradford, United Kingdom, Spectrum Pharmaceuticals Inc, Irvine, CA, NDDO Oncology BV, Amsterdam, Netherlands, and Department of Pathology, Bradford Royal Infirmary, Bradford, United Kingdom.
eoquin (formally known as EO9) is a indolequinone bioreductive drug which despite promising preclinical activity, failed to show efficacy in phase II clinical trials against NSCLC, breast, colorectal, pancreatic and gastric cancers. Poor drug delivery to tumours as a result of a combination of rapid pharmacokinetic elimination and relatively poor penetration through avascular tissue has been suggested as the principle reason for eoquin?s lack of clinical efficacy to date (Phillips et al, Br J Cancer 77; 2112-2119, 1998). The rational for this study is that intravesical administration of eoquin would circumvent the drug delivery problem and any drug reaching the blood stream would be rapidly cleared thereby reducing the risk of systemic toxicity. The primary objective of this study was to determine the safe dose of eoquin for phase II clinical trials. Six patients have entered the study, all of which had received prior chemotherapy and had recurrent low grade (G1/G2) multiple superficial (Ta/T1) bladder tumours. All but one lesion was surgically removed (TUR) with the remaining tumour serving as a marker lesion to assess eoquin efficacy. Two weeks after TUR, patients received escalating doses of eoquin administered intravesically on a weekly schedule for 6 weeks (starting at 0.5 mg/40ml and doubled until toxicity or the maximum dose of 16 mg/40ml was achieved). All patients tolerated up to 4 mg/40ml without adverse events. Two patients experienced local toxicity at 8 mg/40ml (dysuria and haematouria grades 2 and 3, both events were reversible), for which the subsequent dose was reduced to 4 mg/40ml. Both patients tolerated the reduced dose. Four patients received the maximun dose of 16 mg/40ml, 2 of which experienced mild dysuria and haematouria whereas the remaining 2 patients tolerated eoquin at 16 mg/40ml without any toxicity. No systemic side effects were observed and eoquin could not be detected in the plasma (< 20 ng/ml) during and at the end of the instillation. In the urine collected at the end of the one hour instillation, the concentrations of eoquin detected were linear and dose dependent. Two weeks after the last instillation, the effect of eoquin against the marker lesion was determined by cytoscopy. Four out of the 6 patients studied responded to treatment (RR = 66%), which was determined by complete disappearance of the marker lesion assessed by visual inspection and microscopic examination of biopsies taken from the marker lesion site. For the first patient treated, no recurrences have occurred one year after treatment. For the remaining patients who responded to eoquin, no recurrences have occurred up to 6 months after treatment. These preliminary results suggest that intravesical eoquin has activity against superficial bladder cancer and a phase II study (at 4 mg/40ml given weekly for 6 weeks) of intravesical eoquin against superficial bladder cancer is planned.
Wonder if you could try a similar approach to early-stage NSCLC via inhalation? (NSCLC tumors apparently have the same DT-diaphorase activity that is claimed to be the basis for eoquin's efficacy).
Peter |
