Phase I/IIa study of combination chemotherapy with CKD-602 and cisplatin in patients with recurrent epithelial ovarian cancer

Ann N Y Acad Sci. 2009 Aug:1171:627-34. doi: 10.1111/j.1749-6632.2009.04885.x.

Abstract

The aim of this study was to determine the maximum tolerated dose (MTD) and therapeutic efficacy of a newly developed CKD-602 topoisomerase I inhibitor and cisplatin in patients with recurrent epithelial ovarian cancer. CKD-602 (0.30 mg/m(2) daily for 5 days) and cisplatin (60 mg/m(2) on day 5) were administered to patients every 3 weeks with dose adjustment of CKD-602 by 0.05 mg/m(2) daily until the MTD was reached. Dose-limiting toxicity was defined as grade >or= 3 neutropenia or thrombocytopenia for more than 4 days or accompanied by fever >or= 38.5 degrees C, infection, hemorrhage, or transfusion; grade >or= 3 nonhematological toxicity except for alopecia, nausea, and vomiting. We enrolled 26 patients with recurrent epithelial ovarian cancer who had measurable disease (MD) estimated by computed tomography scan (n= 12) and nonmeasurable disease (NMD) evaluated by serum CA-125 levels (n= 14). All patients received 188 cycles of CKD-602 and cisplatin with a median number of six cycles per patient (range, 2 to 12). MTD of CKD-602 was 0.30 mg/m(2) daily. The overall response rate was 69.2% (18/26) with 58.3% (7/12) and 78.6% (11/14) in MD and NMD, respectively. Among the responsive patients, 14 were platinum sensitive (14/18, 77.7%) and four were platinum resistant (4/8, 50.0%). The most common toxicity was grade >or= 3 neutropenia developing in 17 patients (65.4%) and 72 cycles (38.3%). Grade 3 nausea and anorexia were the most common gastrointestinal toxicities, developing in 15 cycles (8.0%) of four patients (15.4%) and 10 cycles (5.3%) of five patients (19.3%), respectively. The median disease-free interval was 6 months (range 0-26 months). CKD-602 at a concentration of 0.3 mg/m(2) daily for 5 days and cisplatin at 60 mg/m(2) on day 5 every 3 weeks showed high efficacy, with acceptable toxicity, against platinum-sensitive/resistant recurrent epithelial ovarian cancer.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anemia / chemically induced
  • Anorexia / chemically induced
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Leukopenia / chemically induced
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Neutropenia / chemically induced
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Treatment Outcome

Substances

  • belotecan
  • Cisplatin
  • Camptothecin