Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions.

Abstract

Pancreatic cancer (PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor. Recently PDAC stroma has been addressed as a potential therapeutic target. Nano albumin bound (Nab)-paclitaxel is an innovative molecule depleting tumor stroma, through interaction between albumin and secreted protein acidic and rich in cysteine. Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phase III study. This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules. Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC. In this article, we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research. Furthermore, we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials.

• Authors: Guido Giordano, Massimo Pancione, Nunzio Olivieri, Pietro Parcesepe, Marianna Velocci, Tania Di Raimo, Luigi Coppola, Giuseppe Toffoli, Mario Rosario D'Andrea
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 23 Issue 32 Pg. 5875-5886 (Aug 28 2017) ISSN: 2219-2840 [Electronic] United States
• PMID: 28932079 (Publication Type: Journal Article, Review)

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Antineoplastic Agents, Phytogenic
• Osteonectin
• Deoxycytidine
• Paclitaxel
• Gemcitabine

Topics

• Albumins (metabolism, pharmacokinetics, therapeutic use)
• Antineoplastic Agents, Phytogenic (pharmacokinetics, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (pharmacokinetics, therapeutic use)
• Carcinoma, Pancreatic Ductal (drug therapy, mortality, pathology)
• Clinical Trials as Topic
• Deoxycytidine (analogs & derivatives, pharmacokinetics, therapeutic use)
• Disease-Free Survival
• Humans
• Neoplasm Staging
• Osteonectin (metabolism)
• Paclitaxel (pharmacokinetics, therapeutic use)
• Pancreas (metabolism, pathology)
• Pancreatic Neoplasms (drug therapy, mortality, pathology)
• Permeability
• Treatment Outcome
• Gemcitabine