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

Hee Seung Kim, Sok Bom Kang, Sang Soo Seo, Seung Su Han, Jae Weon Kim, Noh Hyun Park, Soon Beom Kang, Hyo Pyo Lee, Yong Sang Song

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

11 Scopus citations

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/m2 daily for 5 days) and cisplatin (60 mg/m2 on day 5) were administered to patients every 3 weeks with dose adjustment of CKD-602 by 0.05 mg/m2 daily until the MTD was reached. Dose-limiting toxicity was defined as grade ≥ 3 neutropenia or thrombocytopenia for more than 4 days or accompanied by fever ≥ 38.5°C, infection, hemorrhage, or transfusion; grade ≥ 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 ≥ 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/m2 daily for 5 days and cisplatin at 60 mg/m2 on day 5 every 3 weeks showed high efficacy, with acceptable toxicity, against platinum-sensitive/resistant recurrent epithelial ovarian cancer.

Original languageEnglish
Title of host publicationNatural Compounds and Their Role in Apoptotic Cell Signaling Pathways
PublisherBlackwell Publishing Inc.
Pages627-634
Number of pages8
ISBN (Print)9781573317375
DOIs
StatePublished - Aug 2009

Publication series

NameAnnals of the New York Academy of Sciences
Volume1171
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • CKD-602
  • Cisplatin
  • Ovarian cancer
  • Recurrent

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