TY - JOUR
T1 - A phase 2 trial of flavopiridol (Alvocidib) and cisplatin in platin-resistant ovarian and primary peritoneal carcinoma
T2 - MC0261
AU - Bible, Keith C.
AU - Peethambaram, Prema P.
AU - Oberg, Ann L.
AU - Maples, William
AU - Groteluschen, David L.
AU - Boente, Matthew
AU - Burton, Jill K.
AU - Gomez Dahl, Leigh C.
AU - Tibodeau, Jennifer D.
AU - Isham, Crescent R.
AU - Maguire, Jacie L.
AU - Shridhar, Viji
AU - Kukla, Andrea K.
AU - Voll, Kalli J.
AU - Mauer, Mathew J.
AU - Colevas, Alexander D.
AU - Wright, John
AU - Doyle, L. Austin
AU - Erlichman, Charles
N1 - Funding Information:
This work was supported by National Cancer Institute CM17104, CA097129, CA15083 and CM62205; Clinicaltrials.gov identifier: NCT00083122.
PY - 2012/10
Y1 - 2012/10
N2 - Purpose: Based upon promising preclinical and phase 1 trial results, combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers. Methods: A two cohort phase 2 trial of cisplatin (60 mg/m2 IV) immediately followed by flavopiridol (100 mg/m2 IV, 24 h infusion; 21 day cycles) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease (progression > vs. ≤ 6 months following prior platin-based therapy). Measurable disease (RECIST) - or evaluable disease plus CA125 > 2X post-treatment nadir - and ECOG performance ≤ 2 were required. Results: Forty-five patients were enrolled between December 23, 2004 and February 25, 2010: 40 platin-resistant (Group 1), and 5 platin-sensitive (Group 2). In Group 1, the median number of treatment cycles was 3 (range 2-12). Only 10% of patients incurred grade 4 toxicities, but grade 3 toxicities were common (65%): neutropenia (17.5%); nausea (12.5%); vomiting, fatigue, thrombosis, anemia (10% each). Seven patients (17.5%) achieved a confirmed response (1 CR, 6 PR; median duration 118 days); ten additional patients (25%) attained maintained stable disease. Median time to progression was 4.3 months; overall survival was 16.1 months. Pilot translational studies assessed ascites flavopiridol level; surrogate marker studies were uninformative. In Group 2, although 4 of 5 patients responded (2 confirmed PRs with median time to progression, 10.8 months and median overall survival 20.6 months) the cohort was closed due to poor accrual. Conclusions: The assessed flavopiridol and cisplatin regimen displayed clinical activity in platin resistant and sensitive ovarian/primary peritoneal cancers, meriting further study.
AB - Purpose: Based upon promising preclinical and phase 1 trial results, combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers. Methods: A two cohort phase 2 trial of cisplatin (60 mg/m2 IV) immediately followed by flavopiridol (100 mg/m2 IV, 24 h infusion; 21 day cycles) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease (progression > vs. ≤ 6 months following prior platin-based therapy). Measurable disease (RECIST) - or evaluable disease plus CA125 > 2X post-treatment nadir - and ECOG performance ≤ 2 were required. Results: Forty-five patients were enrolled between December 23, 2004 and February 25, 2010: 40 platin-resistant (Group 1), and 5 platin-sensitive (Group 2). In Group 1, the median number of treatment cycles was 3 (range 2-12). Only 10% of patients incurred grade 4 toxicities, but grade 3 toxicities were common (65%): neutropenia (17.5%); nausea (12.5%); vomiting, fatigue, thrombosis, anemia (10% each). Seven patients (17.5%) achieved a confirmed response (1 CR, 6 PR; median duration 118 days); ten additional patients (25%) attained maintained stable disease. Median time to progression was 4.3 months; overall survival was 16.1 months. Pilot translational studies assessed ascites flavopiridol level; surrogate marker studies were uninformative. In Group 2, although 4 of 5 patients responded (2 confirmed PRs with median time to progression, 10.8 months and median overall survival 20.6 months) the cohort was closed due to poor accrual. Conclusions: The assessed flavopiridol and cisplatin regimen displayed clinical activity in platin resistant and sensitive ovarian/primary peritoneal cancers, meriting further study.
KW - CDK
KW - Cyclin dependent kinase
KW - Stat-3
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U2 - 10.1016/j.ygyno.2012.05.030
DO - 10.1016/j.ygyno.2012.05.030
M3 - Article
C2 - 22664059
AN - SCOPUS:84865680221
SN - 0090-8258
VL - 127
SP - 55
EP - 62
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 1
ER -