Metastatic pancreatic adenocarcinoma associated with chronic calcific pancreatitis and a heterozygous SPINK1 N34S mutation

Pancreatology ◽  
2016 ◽  
Vol 16 (5) ◽  
pp. 869-872 ◽  
Author(s):  
Robert A. Moran ◽  
Robert Klapheke ◽  
Niloofar Y. Jalaly ◽  
Martin A. Makary ◽  
Kenzo Hirose ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Chronic Calcific Pancreatitis ◽  
N34s Mutation ◽  
Calcific Pancreatitis

Metastatic Pancreatic Adenocarcinoma in a Patient With Chronic Calcific Pancreatitis and a Heterozygous SPINK1 c.194+2T>C Mutation

Pancreas ◽  
2018 ◽  
Vol 47 (4) ◽  
pp. e24-e25 ◽  
Author(s):  
Tina Boortalary ◽  
Niloofar Y. Jalaly ◽  
Robert A. Moran ◽  
Martin A. Makary ◽  
Christi Walsh ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Chronic Calcific Pancreatitis ◽  
Calcific Pancreatitis

Biologically optimized schedule of gemcitabine and nab-paclitaxel regimen in metastatic pancreatic adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4168-TPS4168
Author(s):  
Laith I. Abushahin ◽  
Anne M. Noonan ◽  
John L. Hays ◽  
Pannaga G. Malalur ◽  
Ashish Manne ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Dose Intensity ◽  
Standard Of Care ◽  
Significance Level ◽  
Pancreatic Cancer Cells ◽  
Metastatic Pancreatic Adenocarcinoma

TPS4168 Background: Metastatic pancreatic adenocarcinoma has a poor prognosis, and improvements in therapy have been challenging. Alongside efforts in developing novel agents, there is a need to optimize and maximize the benefit of currently approved drugs. Gemcitabine + nab-paclitaxel is a frequently used regimen for pancreatic adenocarcinoma. Nab-paclitaxel is albumin–bound chemotherapy; hence the role of albumin uptake is critical for its effect. Caveolae are small membrane invaginations essential for transendothelial albumin uptake. Cav-1 is the principal structural component of caveolae. Williams and colleagues have published a series of preclinical studies demonstrating that tumor cell-specific Cav-1 expression directly correlates with albumin and albumin-bound chemotherapy uptake and subsequent apoptotic response in tumor cells. In vitro studies showed that exposure of pancreatic cancer cells to Gemcitabine resulted in up-regulation of Cav-1 peaking 48 hours after gemcitabine exposure. This Cav-1 up-regulation correlated with increased temporal albumin cellular uptake. In addition, Williams and colleagues noted that exposure of pancreatic cancer cell lines to Gemcitabine resulted in a time–specific re-entry of cells into the G2/M phase (nab-paclitaxel cytotoxicity phase) between 48-60 hours after gemcitabine treatment. Collectively this data suggest that infusing nab-paclitaxel after 48 hours of gemcitabine infusion would be optimal for both increased uptake as well as increased susceptible tumor cells. We had previously shown this effect on multiple cell lines as well as mouse models. Methods: This is a phase II trial; patients will receive a standard of care chemotherapy regimen consisting of FDA-approved Gemcitabine + nab-paclitaxel with modification of the schedule to deliver nab-paclitaxel 48 hours (2 days) after gemcitabine infusions. The primary endpoint is ORR, with a null hypothesis of 20% vs. a target of 35%. Employing a 2-stage design (minimax) and assuming 80% power and a 0.05 significance level, a total of 53 patients will be required. In the first stage, if at least 7/31 patients respond to therapy, an additional 22 patients will be added for a total of 53 patients. The study will be terminated early if ≤ six patients respond in the first stage. Observation of response in at least 16/53 patients would be required to warrant further investigation of this infusion schedule of combination therapy. The secondary endpoints include the safety of the regimen schedule, Relative dose intensity, disease control rate, PFS, and OS. The trial opened to enrollment in June 2020 and is accepting patients. Clinical trial information: NCT04115163.

scholarly journals Exceptional Response to Second-Line Gemcitabine/Nab-Paclitaxel Chemotherapy in Patients With Metastatic Pancreatic Adenocarcinoma

Cureus ◽  
2021 ◽  
Author(s):  
Nedal Bukhari ◽  
Khalda Abdalla ◽  
Fahad Ibnshamsa ◽  
Waleed Alselwi ◽  
Shakir Al-Shakir ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Second Line ◽  
Metastatic Pancreatic Adenocarcinoma
Sign in / Sign up

Export Citation Format

Share Document