Dataset Information

Comparing routes of delivery for nanoliposomal irinotecan shows superior anti-tumor activity of local administration in treating intracranial glioblastoma xenografts.

ABSTRACT:

Background

Liposomal drug packaging is well established as an effective means for increasing drug half-life, sustaining drug activity, and increasing drug efficacy, whether administered locally or distally to the site of disease. However, information regarding the relative effectiveness of peripheral (distal) versus local administration of liposomal therapeutics is limited. This issue is of importance with respect to the treatment of central nervous system cancer, for which the blood-brain barrier presents a significant challenge in achieving sufficient drug concentration in tumors to provide treatment benefit for patients.

Methods

We compared the anti-tumor activity and efficacy of a nanoliposomal formulation of irinotecan when delivered peripherally by vascular route with intratumoral administration by convection-enhanced delivery (CED) for treating intracranial glioblastoma xenografts in athymic mice.

Results

Our results show significantly greater anti-tumor activity and survival benefit from CED of nanoliposomal irinotecan. In 2 of 3 efficacy experiments, there were animal subjects that experienced apparent cure of tumor from local administration of therapy, as indicated by a lack of detectable intracranial tumor through bioluminescence imaging and histopathologic analysis. Results from investigating the effectiveness of combination therapy with nanoliposomal irinotecan plus radiation revealed that CED administration of irinotecan plus radiation conferred greater survival benefit than did irinotecan or radiation monotherapy and also when compared with radiation plus vascularly administered irinotecan.

Conclusions

Our results indicate that liposomal formulation plus direct intratumoral administration of therapeutic are important for maximizing the anti-tumor effects of irinotecan and support clinical trial evaluation of this therapeutic plus route of administration combination.

SUBMITTER: Chen PY

PROVIDER: S-EPMC3548589 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Publications

Comparing routes of delivery for nanoliposomal irinotecan shows superior anti-tumor activity of local administration in treating intracranial glioblastoma xenografts.

Chen Pin-Yuan PY Ozawa Tomoko T Drummond Daryl C DC Kalra Ashish A Fitzgerald Jonathan B JB Kirpotin Dmitri B DB Wei Kuo-Chen KC Butowski Nicholas N Prados Michael D MD Berger Mitchel S MS Forsayeth John R JR Bankiewicz Krystof K James C David CD

Neuro-oncology 20121221 2

<h4>Background</h4>Liposomal drug packaging is well established as an effective means for increasing drug half-life, sustaining drug activity, and increasing drug efficacy, whether administered locally or distally to the site of disease. However, information regarding the relative effectiveness of peripheral (distal) versus local administration of liposomal therapeutics is limited. This issue is of importance with respect to the treatment of central nervous system cancer, for which the blood-bra ...[more]

PMID: 23262509

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Project description:BACKGROUND:Effective treatment options for advanced pancreatic cancer are finite. NAPOLI-1, a phase III randomized trial, demonstrated the efficacy of nanoliposomal irinotecan with fluorouracil/leucovorin (nal-IRI?+?5-FU/LV) for the treatment of advanced pancreatic cancer following progression on gemcitabine-based chemotherapy. There are limited additional data on the safety and efficacy of nal-IRI?+?5-FU/LV following FDA approval in October 2015. We examined the post-approval safety and effectiveness of nal-IRI?+?5-FU/LV in advanced pancreatic cancer patients receiving treatment at Memorial Sloan Kettering Cancer Center. METHODS:A retrospective chart review was conducted of all patients beginning treatment with nal-IRI?+?5-FU/LV from October 2015 through June 2017. Using the electronic medical record and institutional database, information was extracted pertaining to demographics, performance status (ECOG), prior therapies, dose, duration of treatment, adverse events, progression free survival (PFS), overall survival (OS) and treatment response. RESULTS:Fifty six patients were identified. Median progression free survival (PFS) was 2.9 months and median overall survival (OS) was 5.3 months. Patients with prior disease progression on irinotecan experienced PFS and OS of 2.2 and 3.9 mo, respectively. Patients without prior irinotecan exposure experienced significantly longer PFS (4.8 mo, p?=?0.02) and OS (7.7 mo, p?=?0.002), as did patients who received prior irinotecan without disease progression (PFS, 5.7 mo, p?=?0.04; OS, 9.0 mo, p?=?.04). Progression on prior irinotecan was associated with greater lines of prior advanced disease chemotherapy (2 vs 1). Dose reductions (DR) were most frequently due to fatigue (42%) and diarrhea (37%), but were not associated with worse outcomes. In fact, patients with ?1 DR experienced longer PFS (5.4 v 2.6 mo, p?=?0.035). Sequential therapy with nab-paclitaxel + gemcitabine (nab-P?+?Gem) followed by nal-IRI?+?5-FU/LV (n?=?25) resulted in OS of 23.0 mo. Mutations in TP53 were associated with shorter PFS. CONCLUSIONS:These data support the safety and efficacy of nal-IRI?+?5-FU/LV, reinforcing results of NAPOLI-1. Patients without disease progression on prior irinotecan fared significantly better than patients with progression, when treated with nal-IRI?+?5-FU/LV. Sequential therapy with nab-P?+?Gem followed by nal-IRI?+?5-FU/LV demonstrates encouraging median OS. These findings provide guidance for patients most likely to benefit from nal-IRI?+?5-FU/LV.

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Dataset Information

Comparing routes of delivery for nanoliposomal irinotecan shows superior anti-tumor activity of local administration in treating intracranial glioblastoma xenografts.

Background

Methods

Results

Conclusions

Publications

Comparing routes of delivery for nanoliposomal irinotecan shows superior anti-tumor activity of local administration in treating intracranial glioblastoma xenografts.

Similar Datasets

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