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Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience

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 g...

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Autores principales: Glassman, Danielle C., Palmaira, Randze L., Covington, Christina M., Desai, Avni M., Ku, Geoffrey Y., Li, Jia, Harding, James J., Varghese, Anna M., O’Reilly, Eileen M., Yu, Kenneth H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020418/
https://www.ncbi.nlm.nih.gov/pubmed/29945562
http://dx.doi.org/10.1186/s12885-018-4605-1
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author Glassman, Danielle C.
Palmaira, Randze L.
Covington, Christina M.
Desai, Avni M.
Ku, Geoffrey Y.
Li, Jia
Harding, James J.
Varghese, Anna M.
O’Reilly, Eileen M.
Yu, Kenneth H.
author_facet Glassman, Danielle C.
Palmaira, Randze L.
Covington, Christina M.
Desai, Avni M.
Ku, Geoffrey Y.
Li, Jia
Harding, James J.
Varghese, Anna M.
O’Reilly, Eileen M.
Yu, Kenneth H.
author_sort Glassman, Danielle C.
collection PubMed
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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4605-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-60204182018-07-06 Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience Glassman, Danielle C. Palmaira, Randze L. Covington, Christina M. Desai, Avni M. Ku, Geoffrey Y. Li, Jia Harding, James J. Varghese, Anna M. O’Reilly, Eileen M. Yu, Kenneth H. BMC Cancer Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4605-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-27 /pmc/articles/PMC6020418/ /pubmed/29945562 http://dx.doi.org/10.1186/s12885-018-4605-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Glassman, Danielle C.
Palmaira, Randze L.
Covington, Christina M.
Desai, Avni M.
Ku, Geoffrey Y.
Li, Jia
Harding, James J.
Varghese, Anna M.
O’Reilly, Eileen M.
Yu, Kenneth H.
Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience
title Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience
title_full Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience
title_fullStr Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience
title_full_unstemmed Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience
title_short Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience
title_sort nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020418/
https://www.ncbi.nlm.nih.gov/pubmed/29945562
http://dx.doi.org/10.1186/s12885-018-4605-1
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