Phase i study of nanoliposomal irinotecan (PEP02) in advanced solid tumor patients

T. C. Chang, H. S. Shiah, C. H. Yang, K. H. Yeh, A. L. Cheng, B. N. Shen, Y. W. Wang, C. G. Yeh, N. J. Chiang, J. Y. Chang, L. T. Chen

Research output: Contribution to journalArticlepeer-review

87 Citations (Scopus)


Purpose: To define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of PEP02, a novel liposome-encapsulated irinotecan, in patients with advanced refractory solid tumors. Methods: Patients were enrolled in cohorts of one to three to receive escalating dose of PEP02 in a phase I trial. PEP02, from 60 to 180 mg/m2, was given as a 90-min intravenous infusion, every 3 weeks. Results: A total of 11 patients were enrolled into three dose levels: 60 (one patient), 120 (six patients) and 180 mg/m2 (four patients). DLT was observed in three patients, one at 120 mg/m2 (grade 3 catheter-related infection) and two at 180 mg/m2 (grade 4 neutropenia lasting for >3 days in one, grade 4 hematological toxicities and grade 4 diarrhea in the other). MTD was determined as 120 mg/m2. Comparing with those after free-form irinotecan in the literature, the dose-normalized PK of SN-38 (the active metabolite) after PEP02 was characterized by lower C max, prolonged terminal half-life and higher AUC but with significant inter-individual variation. One patient who died of treatment-related toxicity had significantly higher C max and AUC levels of SN-38 than those of the other three patients at 180 mg/m2. Post hoc pharmacogenetic study showed that the patient had a combined heterozygosity genotype of UGT1A1∗6/∗28. Two patients had objective tumor response. Conclusions: PEP02 apparently modified the PK parameters of irinotecan and SN-38 by liposome encapsulation. The MTD of PEP02 monotherapy at 3-week interval is 120 mg/m2, which will be the recommended dose for future studies.

Original languageEnglish
Pages (from-to)579-586
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Issue number3
Publication statusPublished - Jan 1 2015


  • Irinotecan sucrosofate
  • Liposome
  • MM-398
  • PEP02
  • Pharmacokinetics
  • UGT1A1 gene

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)


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