nab-Paclitaxel: Novel Clinical and Experimental Evidence in Pancreatic Cancer

A. Neesse; P. Michl; D. A. Tuveson; V. Ellenrieder

doi:10.1055/s-0034-1366002

Zeitschrift für Gastroenterologie, Table of Contents

Z Gastroenterol 2014; 52(4): 360-366
DOI: 10.1055/s-0034-1366002

Übersicht

nab-Paclitaxel: Novel Clinical and Experimental Evidence in Pancreatic Cancer

nab-Paclitaxel: Neue klinische und grundlagenwissenschaftliche Erkenntnisse im Pankreaskarzinom

A. Neesse

¹Department of Gastroenterology, Endocrinology, Infectiology and Metabolism, Philipps University Marburg, Marburg, Germany

,

P. Michl

¹Department of Gastroenterology, Endocrinology, Infectiology and Metabolism, Philipps University Marburg, Marburg, Germany

,

D. A. Tuveson

²Cold Spring Harbor, Laboratory Cold Spring Harbor, NY, USA

,

V. Ellenrieder

¹Department of Gastroenterology, Endocrinology, Infectiology and Metabolism, Philipps University Marburg, Marburg, Germany

› Author Affiliations

Abstract

The past few decades have seen virtually no treatment advances for patients with metastatic pancreatic cancer. Clinical hallmark features of pancreatic ductal adenocarcinoma (PDA) include late symptom onset, invasive growth, early liver and lymph node metastasis, and resistance to available chemotherapies. nab-Paclitaxel (Abraxane^®) is generated through high-pressure homogenization of human albumin and conventional paclitaxel resulting in non-covalently bound, water-soluble albumin-paclitaxel particles with an approximate diameter of 130 nm. Results from the recently completed Metastatic Pancreatic Adenocarcinoma Trial (MPACT) (phase III trial) showed a significant survival benefit for patients treated with nab-paclitaxel in combination with gemcitabine, and this treatment regimen is currently being implemented in national and international guidelines for PDA patients. Therefore, this regimen provides a much needed vantage point of attack for this recalcitrant tumor offering potential new hope for our patients. Mechanisms such as stromal depletion, selective intratumoral accumulation, synergism with gemcitabine metabolism and secreted protein acidic and rich in cysteine (SPARC) mediated anti-tumor activity have been suggested for nab-paclitaxel. This review discusses the clinical and experimental advances of nab-paclitaxel in pancreatic cancer.

Zusammenfassung

In der Behandlung des fortgeschrittenen Pankreaskarzinoms konnten in den letzten Jahrzehnten kaum Fortschritte erzielt werden. Die Erkrankung verursacht häufig erst im fortgeschrittenem Stadium klinische Symptome, die Tumoren wachsen invasiv in umgebende Strukturen und metastasieren frühzeitig in Leber und retroperitoneale Lymphknoten. Die verfügbaren Chemotherapien erzielen bisher nur sehr begrenzte Erfolge und wirken bei den meisten Patienten nicht ausreichend, um einen signifikanten Überlebensvorteil zu erzielen. nab-Paclitaxel (Abraxane^®) ist ein neues Chemotherapeutikum, welches durch Hochdruck-Homogenisierung von humanem Albumin und herkömmlichem Paclitaxel hergestellt wird und aus 130 nm kleinen, wasserlöslichen Albumin-Paclitaxel-Partikel besteht. Eine kürzlich publizierte große internationale Phase-III-Studie hat einen signifikanten Überlebensvorteil für die Kombinationschemotherapie von nab-Paclitaxel und Gemcitabin gegenüber Gemcitabin berichtet, sodass diese Behandlungsoption in nationale und internationale Leitlinien zur Behandlung des fortgeschrittenen Pankreaskarzinoms Eingang finden wird. Dieser Übersichtsartikel beschäftigt sich sowohl mit klinischen als auch experimentellen Erkenntnissen von nab-Paclitaxel im Pankreaskarzinom, insbesondere den potenziellen Wirkmechanismen wie stromale Depletion, secreted protein acidic and rich in cysteine (SPARC) vermittelter Therapieeffekte und selektiver intratumoraler Anreicherung von nab-Palclitaxel.

Schlüsselwörter

Pankreaskarzinom - Therapieresistenz - Medikamentenanflutung - nab-Paclitaxel

Key words

pancreatic cancer - chemoresistance - drug delivery - nab-paclitaxel

Full Text

References

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