Roy A.C.,The Royal Marsden Hospital |
Park S.R.,Research Institute and Hospital |
Cunningham D.,The Royal Marsden Hospital |
Kang Y.K.,University of Ulsan |
And 10 more authors.
Annals of Oncology | Year: 2013
Background: PEP02 is a novel highly stable liposomal nanocarrier formulation of irinotecan. This randomized phase II study evaluated the efficacy and safety of single agent PEP02 compared with irinotecan or docetaxel in the second-line treatment of advanced oesophago-gastric (OG) cancer. Patients and methods: Patients with locally advanced/metastatic disease who had failed one prior chemotherapy regimen were randomly assigned to PEP02 120 mg/m2, irinotecan 300 mg/m2 or docetaxel (Taxotere) 75 mg/m2 every 3 weeks. The primary end point was objective response rate (ORR). Simon's two-stage design was used and the ORR of interest was 20% (α = 0.05, type II error β = 0.10, null hypothesis of ORR was 5%). Results: Forty-four patients per arm received treatment, and 124 were assessable for response. The ORR statistical threshold for the first stage was reached in all arms. In the intent-to-treat (ITT) population, ORRs were 13.6% (6/44), 6.8% (3/44) and 15.9% (7/44) in the PEP02, irinotecan and docetaxel arms, respectively. The median progression-free survival (PFS) and overall survival were similar between the trial arms. Commonest grade 3-4 adverse event reported was diarrhoea in the PEP02 and irinotecan groups (27.3% versus 18.2%). Conclusion: The ORR associated with PEP02 was comparable with docetaxel and numerically greater than that of irinotecan. PEP02 warrants further evaluation in the advanced gastric cancer setting. © The Author 2013.Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source
PharmaEngine Inc. | Date: 2006-07-18
pharmaceuticals and pharmaceutical preparations, namely, pharmaceuticals and pharmaceutical preparations for the treatment of diseases in the field of oncology, for the treatment of infectious diseases, and for the treatment of respiratory diseases; nutritional supplements for medical use.
Ko A.H.,University of California at San Francisco |
Tempero M.A.,University of California at San Francisco |
Shan Y.-S.,National Cheng Kung University |
Su W.-C.,National Cheng Kung University |
And 8 more authors.
British Journal of Cancer | Year: 2013
Background: PEP02, also known as MM-398, is a novel nanoliposomal irinotecan that has improved pharmacokinetics and tumour bio-distribution of the free drug. This phase 2 study evaluated PEP02 monotherapy as second-line treatment for pancreatic cancer. Methods: Patients who had metastatic pancreatic adenocarcinoma, Karnofsky performance status ≥70, and had progressed following gemcitabine-based therapy were eligible. Intravenous injection of PEP02 120 mg m-2 was given every 3 weeks. Simon 2-stage design was used. The primary objective was 3-month survival rate (OS 3-month). Results: A total of 40 patients were enrolled. The most common severe adverse events included neutropenia, abdominal pain, asthenia, and diarrhoea. Three patients (7.5%) achieved an objective response, with an additional 17 (42.5%) demonstrating stable disease for a minimum of two cycles. Ten (31.3%) of 32 patients with an elevated baseline CA19-9 had a >50% biomarker decline. The study met its primary end point with an OS 3-month of 75%, with median progression-free survival and overall survival of 2.4 and 5.2 months, respectively. Conclusion: PEP02 demonstrates moderate antitumour activity with a manageable side effect profile for metastatic, gemcitabine-refractory pancreatic cancer patients. Given the limited treatment options available to this patient population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is currently underway. © 2013 Cancer Research UK. All rights reserved. Source
Chang T.C.,Linkuo Chang Gung Memorial Hospital |
Shiah H.S.,Taipei Medical University Hospital |
Yang C.H.,National Taiwan University Hospital |
Yeh K.H.,National Taiwan University Hospital |
And 12 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2015
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. © 2015 The Author(s). Source
PharmaEngine Inc | Date: 2007-07-24
Vitamin, mineral and dietary supplements; dietary supplements used to improve health and vitality; herbal supplements, Chinese herbal supplements.