Phase i and pharmacokinetic study of pegylated liposomal CKD-602 in patients with advanced malignancies

William C. Zamboni, Suresh Ramalingam, David M. Friedland, Robert P. Edwards, Ronald G. Stoller, Sandra Strychor, Lauren Maruca, Beth A. Zamboni, Chandra P. Belani, Ramesh K. Ramanathan

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61 Scopus citations


Purpose: S-CKD602 is a pegylated liposomal formulation of CKD602, a semisynthetic camptothecin analogue. Pegylated (STEALTH) liposomes can achieve extended drug exposure in plasma and tumor. Based on promising preclinical data, the first phase I study of S-CKD602 was done in patients with refractory solid tumors. Experimental Design: S-CKD602 was administered i.v. every 3 weeks. Modified Fibonacci escalation was used (three to six patients/cohort), and dose levels ranged from 0.1 to 2.5 mg/m 2. Serial plasma samples were obtained over 2 weeks and total (lactone + hydroxyl acid) concentrations of encapsulated, released, and sum total (encapsulated + released) CKD602 measured by liquid chromatography-tandem mass spectrometry. Results: Forty-five patients (21 males) were treated. Medianage, 62 years (range, 33-79 years) and Eastern Cooperative Oncology Group status, 0 to 1 (43 patients) and 2 (2 patients). Dose-limiting toxicities of grade 3 mucositis occurred in one of six patients at 0.3 mg/m 2, grade 3 and 4 bone marrow suppression in two of three patients at 2.5 mg/m 2, and grade 3 febrile neutropenia and anemia in one of six patients at 2.1 mg/m 2. The maximum tolerated dose was 2,1 mg/m 2. Partial responses occurred in two patients with refractory ovarian cancer (1.7 and 2.1 mg/m 2). High interpatient variability occurred in the pharmacokinetic disposition of encapsulated and released CKD602. Conclusions: S-CKD602 represents a promising new liposomal camptothecin analogue with manageable toxicity and promising antitumor activity. Phase II studies of S-CKD602 at 2.1 mg/m 2 i.v, once every 3 weeks are planned. Prolonged plasma exposure over 1 to 2 weeks is consistent with STEALTH liposomes and provides extended exposure compared with single doses of nonliposomal camptothecins.

Original languageEnglish (US)
Pages (from-to)1466-1472
Number of pages7
JournalClinical Cancer Research
Issue number4
StatePublished - Feb 15 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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