Phase II clinical trial of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant ovarian or primary peritoneal cancer: a gynecologic oncology group study.
PURPOSE Ixabepilone (BMS-247550) is a microtubule-stabilizing epothilone B analog with activity in taxane-resistant metastatic breast cancer. The Gynecologic Oncology Group conducted a phase II evaluation of the efficacy and safety of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant primary ovarian or peritoneal carcinoma. PATIENTS AND METHODS Patients with measurable platinum- and taxane-resistant ovarian or peritoneal carcinoma, defined as progression during or within 6 months of one prior course of treatment with each agent, received intravenous ixabepilone 20 mg/m(2) administered over 1 hour on days 1, 8, and 15 of a 28-day cycle. Results Of 51 patients entered, 49 were eligible. The objective response rate was 14.3% (95% CI, 5.9% to 27.2%), with three complete and four partial responses. Twenty patients (40.8%) had stable disease, whereas sixteen (32.7%) had increasing disease. The median time to progression was 4.4 months (95% CI, 0.8 to 32.6+ months); median survival was 14.8 months (95% CI, 0.8 to 50.0) months. Patients received a median of two treatment cycles (range, 1 to 29 cycles), and 18.4% of patients received > or = six cycles. Adverse effects included peripheral grade 2 (28.5%) and grade 3 (6.1%) neuropathy, grades 3 to 4 neutropenia (20.4%), grade 3 fatigue (14.3%), grade 3 nausea/emesis (22%), grade 3 diarrhea (10%), and grade 3 mucositis (4%). CONCLUSION Ixabepilone 20 mg/m(2) over 1 hour on days 1, 8, and 15 of a 28-day cycle demonstrates antitumor activity and acceptable safety in patients with platinum- and taxane-resistant recurrent or persistent ovarian or primary peritoneal carcinoma.
De Geest
Koen
K
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Suite 4630 JCP, Iowa City, IA 52242, USA. koen-degeest@uiowa.edu
Blessing
John A
JA
Morris
Robert T
RT
Yamada
S Diane
SD
Monk
Bradley J
BJ
Zweizig
Susan L
SL
Matei
Daniela
D
Muller
Carolyn Y
CY
Richards
William E
WE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D043823:Taxoids / Q000627:therapeutic use; D050257:Tubulin Modulators / Q000627:therapeutic use*
D001952:Bridged-Ring Compounds; D034261:Epothilones; D009944:Organoplatinum Compounds; D043823:Taxoids; D050257:Tubulin Modulators; C080625:taxane; C430592:ixabepilone