Introduction Gemcitabine monotherapy remained the gold standard in the treatment of advanced pancreatic ductal adenocarcinoma, all this changed with the arrival of Nab-paclitaxel in combination with gemcitabine (NP / G) as a new treatment option for patients with cancer of the metastatic pancreas [1]. Thus, Abraxane or albumin-bound nanoparticles of paclitaxel (Nab-paclitaxel) was approved in 2013 for advanced-stage pancreatic cancer [2]. Thus, there are several studies with NP / G for the treatment of pancreatic cancer. In 2019 the regimen was targeted to elderly patients with metastatic pancreatic cancer, proving to be feasible and effective, as shown in [3]. On the other hand, an investigation compared gemcitabine monotherapy with PN / G in patients with metastatic or locally advanced pancreatic adenocarcinoma, where PN / G showed a higher response rate without toxicity or deterioration of quality of life, see [ 4]. Of course, in [5] there is another study with NP / G for locally advanced pancreatic cancer, finding that it is a good option for chemotherapy, as well as a main regimen in which new targeted agents could be added. Thus, among the most recent systematic reviews, there is one focused on comparing the effectiveness of NP / G and FOLFIRINOX in metastatic pancreatic cancer, where there was no significant benefit of one regimen over the other; while the other deals with the effectiveness of NP / G as a first-line treatment for advanced pancreatic cancer, showing mild side effects compared to FOLFIRINOX [6], [7]. Also, other drugs have been added to the NP / G regimen, including targeted therapy and chemotherapy to treat pancreatic cancer. Thus, these drug combinations are widely used because they affect multiple targets and cell subpopulations, aiming to kill cancer cells with high selectivity [8]. Research Question Which of the formulations of the nab-paclitaxel / gemcitabine regimen in combination with other drugs has been safest in patients with pancreatic cancer? Inclusion criteria (1) Studies involving patients with advanced or metastatic pancreatic cancer. (2) Studies with patients from 18 years of age. (3) Studies where the NP / G regimen is combined with other drugs for the treatment of pancreatic cancer. (5) Indication of the dose used, adverse events, overall survival and progression-free survival of the formulation. (6) Studies indicating any of the following clinical events: objective response rate, complete response, or partial response to treatment. Exclusion criteria (1) Non-clinical research such as reviews, meta-analyzes, and systematic reviews. (2) Articles not written in English. (3) Articles with a publication date less than 2015. (4) Articles where the formulation does not contain the main NP / G regimen. (5) Studies that address another type of cancer. (6) Phases of minor clinical trials by the same author or working group General objective • To compare the safety of the different formulations that include the Nab-paclitaxel / gemcitabine regimen in combination with other drugs for the treatment of pancreatic cancer. Specific objectives • To determine databases offered at the UACJ and CONRICyT that include scientific and clinical information regarding cancer. • To select the articles according to the inclusion and exclusion criteria. • To collect the necessary information in each article where the NP / G regimen is used in combination with other drugs for the treatment of pancreatic cancer. • To conclude on which formulation of NP / G in combination with other drugs is safer in patients with pancreatic cancer. Justification for the study Because pancreatic cancer does not present symptoms initially, it is usually detected in advanced stages (locally advanced and metastatic), which has caused a high mortality in patients with this disease. Therefore, the present systematic review aims to carry out an investigation about the efficacy of nab-paclitaxel / gemcitabine therapy in combination with other drugs for the treatment of said cancer, where it will be concluded which of these formulations it is safer. In this way, through the analysis of different clinical events, obtained from articles collected from databases with clinical research on cancer, it will be possible to determine the safety and efficacy offered by the nab-paclitaxel / gemcitabine regimen with monoclonal antibody drugs, chemotherapy, tyrosine kinase inhibitors, among others, to treat pancreatic cancer. Thus, the information obtained in this review will reveal a formulation that could be a safe treatment alternative for this currently challenging disease. Proposed methodology 1. Choice of databases: Science Direct, Web of Science, PubMed. 2. Selection of search terms with Booleans to find the bibliography regarding the topic: (Nab-paclitaxel OR “nanoparticle albumin-bound paclitaxel”) AND ("Pancreatic Cancer" OR "Metastatic Pancreatic Cancer" OR "Pancreatic adenocarcinoma") AND ( Gemcitabine) AND (Chemotherapy) AND ("Clinical trial"). 3. Preparation of a prism flow diagram for the selection of articles to include in the systematic review. 4. Extraction and synthesis of important data from each article: drug and dose used, adverse events, overall survival, partial response to treatment, etc. 5. Analysis and conclusion on the data collected regarding which is the safest formulation of NP / G in combination with other drugs in the treatment of pancreatic cancer. 6. Preparation of the systematic review document with the information summarized and ordered

{"references": ["[1] H. Blomstrand, U. Scheibling, C. Bratth\u00e4ll, H. Green, and N. O. Elander, \"Real world evidence on gemcitabine and nab-paclitaxel combination chemotherapy in advanced pancreatic cancer,\" BMC Cancer, vol. 19, no. 1, pp. 1\u20139, 2019, doi: 10.1186/s12885-018-5244-2", "[2] V. M. Khot, A. B. Salunkhe, S. Pricl, J. Bauer, N. D. Thorat, and H. Townley, \"Nanomedicine-driven molecular targeting, drug delivery, and therapeutic approaches to cancer chemoresistance,\" Drug Discov. Today, \"In Press\", doi: 10.1016/j.drudis.2020.12.016.", "[3] A. Petrillo et al., \"First line nab-paclitaxel plus gemcitabine in elderly metastatic pancreatic patients: A good choice beyond age,\" J. Gastrointest. Oncol., vol. 10, no. 5, pp. 910\u2013917, 2019, doi: 10.21037/jgo.2019.06.02.", "[4] S. Yalcin et al., \"Quality of life study of patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma treated with gemcitabine+nab-paclitaxel versus gemcitabine alone: AX-PANC-SY001, a randomized phase-2 study,\" BMC Cancer, vol. 20, no. 1, pp. 1\u20137, 2020, doi: 10.1186/s12885-020-06758-9", "[5] P. A. Philip et al., \"Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study,\" Lancet Gastroenterol. Hepatol., vol. 5, no. 3, pp. 285\u2013294, 2020, doi: 10.1016/S2468-1253(19)30327-9.", "[6] S. Pusceddu et al., \"Comparative effectiveness of gemcitabine plus nab-paclitaxel and folfirinox in the first-line setting of metastatic pancreatic cancer: A systematic review and meta-analysis,\" Cancers (Basel)., vol. 11, no. 4, 2019, doi: 10.3390/cancers11040484", "[7] Y. Zhang et al., \"Nab-paclitaxel plus gemcitabine as first-line treatment for advanced pancreatic cancer: A systematic review and meta-analysis,\" J. Cancer, vol. 10, no. 18, pp. 4420\u20134429, 2019, doi: 10.7150/jca.29898", "[8] Y. Qian et al., \"Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma,\" J. Hematol. Oncol., vol. 13, no. 1, pp. 1\u201320, 2020, doi: 10.1186/s13045-020-00958-3."]}

(EN) Presentation of the review research protocol by Karina López Juárez, student of the Biomedical Engineering program at the Autonomous University of Ciudad Juárez. Advisor: Dr. Christian Chapa. Correspondence: christian.chapa@uacj.mx | Presentación del protocolo de investigación de revisión por Karina López Juárez, estudiante del programa de Ingeniería Biomédica de la Universidad Autónoma de Ciudad Juárez. Asesor: Dr. Christian Chapa. Correspondencia: christian.chapa@uacj.mx