BACKGROUND: It has been postulated that protein kinase C alpha (PKC-alpha) plays a pivotal role in signal transduction in tumor cancer cells. Aprinocarsen, a 20-base antisense oligonucleotide, has shown ability to inhibit PKC-alpha protein expression and inhibit tumor growth in human xenograft models. In a previous Phase I trial, the authors demonstrated the safety and some evidence of activity in ovarian carcinoma of aprinocarsen administered as a 21-day, continuous, intravenous infusion. METHODS: In this Phase II trial, 36 patients with advanced ovarian carcinoma were treated with aprinocarsen at a dose of 2 mg/kg per day delivered as a 21-day, continuous, intravenous infusion. The primary objective was to determine the antitumor response, and the secondary objectives were to evaluate toxicity and to evaluate effects on quality of life (QOL). RESULTS: Between September 1997 and December 1999, 36 patients (median age, 58 years) were enrolled in this trial. Patients were stratified into 2 groups: a platinum-sensitive group (n = 12 patients) and a platinum-resistant group (n = 24 patients). All 36 patients were evaluable for toxicity, and 27 patients were fully assessable for antitumor response after 2 cycles of therapy. All patients had received prior treatments. No objective responses were noted in the platinum-sensitive group. In the platinum-resistant group, 1 patient had some evidence of antitumor activity indicated by a decrease in serum CA 125 and stable disease on imaging studies for 8 months. No changes were noted in overall patient ratings for any of the five QOL domains. CONCLUSIONS: When it was administered as a single agent, aprinocarsen did not have significant clinical activity in patients with advanced ovarian carcinoma. Further study may be warranted in combination with platinum-based regimens. Copyright 2003 American Cancer Society.
BACKGROUND: It has been postulated that protein kinase C alpha (PKC-alpha) plays a pivotal role in signal transduction in tumor cancer cells. Aprinocarsen, a 20-base antisense oligonucleotide, has shown ability to inhibit PKC-alpha protein expression and inhibit tumor growth in human xenograft models. In a previous Phase I trial, the authors demonstrated the safety and some evidence of activity in ovarian carcinoma of aprinocarsen administered as a 21-day, continuous, intravenous infusion. METHODS: In this Phase II trial, 36 patients with advanced ovarian carcinoma were treated with aprinocarsen at a dose of 2 mg/kg per day delivered as a 21-day, continuous, intravenous infusion. The primary objective was to determine the antitumor response, and the secondary objectives were to evaluate toxicity and to evaluate effects on quality of life (QOL). RESULTS: Between September 1997 and December 1999, 36 patients (median age, 58 years) were enrolled in this trial. Patients were stratified into 2 groups: a platinum-sensitive group (n = 12 patients) and a platinum-resistant group (n = 24 patients). All 36 patients were evaluable for toxicity, and 27 patients were fully assessable for antitumor response after 2 cycles of therapy. All patients had received prior treatments. No objective responses were noted in the platinum-sensitive group. In the platinum-resistant group, 1 patient had some evidence of antitumor activity indicated by a decrease in serum CA 125 and stable disease on imaging studies for 8 months. No changes were noted in overall patient ratings for any of the five QOL domains. CONCLUSIONS: When it was administered as a single agent, aprinocarsen did not have significant clinical activity in patients with advanced ovarian carcinoma. Further study may be warranted in combination with platinum-based regimens. Copyright 2003 American Cancer Society.
Authors: Ted S Gross; Katy A King; Natalia A Rabaia; Pranali Pathare; Sundar Srinivasan Journal: J Bone Miner Res Date: 2004-10-11 Impact factor: 6.741
Authors: Lydia Usha; Michael W Sill; Kathleen M Darcy; Doris M Benbrook; Jean A Hurteau; David P Michelin; Robert S Mannel; Parviz Hanjani; Koen De Geest; Andrew K Godwin Journal: Gynecol Oncol Date: 2011-03-17 Impact factor: 5.482
Authors: Stephen I Shibata; James H Doroshow; Paul Frankel; Timothy W Synold; Yun Yen; David R Gandara; Heinz-Josef Lenz; Warren A Chow; Lucille A Leong; Dean Lim; Kim A Margolin; Robert J Morgan; George Somlo; Edward M Newman Journal: Cancer Chemother Pharmacol Date: 2009-03-26 Impact factor: 3.333