A phase I dose-escalation study of PEP02 (irinotecan liposome injection) in combination with 5-fluorouracil and leucovorin in advanced solid tumors

BMC Cancer

Research Article

Ruey-Kuen Hsieh¹  Tsu-Yi Chao²  Cheng-Hsu Wang³  Nai-Jung Chiang⁴  Li-Tzong Chen⁵  Yi-Wen Wang⁶  C. Grace Yeh⁶ 

[1] Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan;Division of Hematology and Oncology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan;Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan;National Institute of Cancer Research, National Health Research Institutes, 2F, No. 367, Sheng-Li Road, 704, Tainan, Taiwan;Division of Hematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan;National Institute of Cancer Research, National Health Research Institutes, 2F, No. 367, Sheng-Li Road, 704, Tainan, Taiwan;Division of Hematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan;Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan;PharmaEngine, Inc, Taipei, Taiwan;

关键词: Liposomal irinotecan;    5-fluorouracil;    Dose-limiting toxicity;    Maximum tolerated dose;   

DOI  :  10.1186/s12885-016-2933-6

 received in 2016-03-02, accepted in 2016-10-28,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundPEP02 (also known as MM-398, nal-IRI) is a novel nanoparticle formulation of irinotecan encapsulated in liposomes. The aims of this study were to investigate the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of PEP02 in combination with 5-FU and LV, in patients with advanced refractory solid tumors.MethodsPatients were enrolled in cohorts to receive PEP02 from 60 to 120 mg/m2 (dose expressed as the irinotecan hydrochloride trihydrate salt) as a 90-min intravenous infusion on day 1, followed by 24 h infusion of 5-FU 2,000 mg/m2 and LV 200 mg/m2 on days 1 and 8, every 3 weeks.ResultsA total of 16 patients were assigned to four dose levels, 60 (three patients), 80 (six patients), 100 (five patients) and 120 mg/m2 (two patients). DLT was observed in four patients, two at the 100 mg/m2 dose level (one had grade III infection with hypotension and grade III hemorrhage; the other had grade III diarrhea and grade IV neutropenia), and two at the 120 mg/m2 dose level (one had grade III diarrhea and grade IV neutropenia; the other had grade III diarrhea). The MTD of PEP02 was determined as 80 mg/m2. The most common treatment-related adverse events were nausea (81%), diarrhea (75%) and vomiting (69%). Among the six patients who received the MTD, one patient exhibited partial response, four patients had stable disease and one showed progressive disease. Pharmacokinetic data showed that PEP02 had a lower peak plasma concentration, longer half-life, and increased area under the plasma concentration-time curve from zero to time t of SN-38 than irinotecan at similar dose level.ConclusionsThe MTD of PEP02 on day 1 in combination with 24-h infusion of 5-FU and LV on days 1 and 8, every 3 weeks was 80 mg/m2, which will be the recommended dose for future studies.Trial registrationThe trial was retrospectively registered (NCT02884128) with date of registration: August 12, 2016.

【 授权许可】

CC BY   
© The Author(s). 2016