Multi-pathway cholesterol depletion on top of FOLFIRINOX in newly-diagnosed metastatic pancreatic adenocarcinoma

2021 ◽  
Vol 15 (5) ◽  
pp. e18
Author(s):  
Anne Gangloff ◽  
Maxime Chénard-Poirier ◽  
Frédéric Calon ◽  
Félix Couture ◽  
Nabil Seidah
2015 ◽  
Vol 8 (1) ◽  
pp. 138-141 ◽  
Author(s):  
Manisha Chandar ◽  
Robert de Wilton Marsh

Background: Irinotecan is commonly used in combination with oxaliplatin as a component of FOLFIRINOX chemotherapy for several gastrointestinal malignancies. The purpose of this case report is to describe a patient who developed acute paralysis and aphasia while receiving her initial infusion of irinotecan. Case Report: A 67-year-old woman with newly diagnosed metastatic pancreatic adenocarcinoma presented for her first cycle of FOLFIRINOX chemotherapy. During her infusion of irinotecan, she developed acute onset of generalized weakness, paralysis of all extremities, and nonfluent aphasia with complete inability to communicate. This episode was self-limited and resolved within 2 h. Prior to subsequent infusions she received intravenous repletion of potassium and had no recurrence of symptoms. Discussion: In selected cases, coadministration of irinotecan and oxaliplatin may result in severe generalized weakness and aphasia, which may be triggered by underlying electrolyte disturbances. Careful monitoring and correction of potassium may help prevent this reaction.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244487
Author(s):  
Chia-Yu Chen ◽  
Shih-Hsin Liang ◽  
Yung-Yeh Su ◽  
Nai-Jung Chiang ◽  
Hui-Ching Wang ◽  
...  

Background In pancreatic cancer, toxicities associated with current chemotherapeutic regimens remain concerning. A modified combination of gemcitabine, S-1, and leucovorin (GSL) was used as the first-line treatment for newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma patients. Methods GSL was administered every 2 weeks—intravenous gemcitabine 800 mg/m2 at a fixed-dose rate of 10 mg/m2/min on day 1 and oral S-1 (80–120 mg/day) plus leucovorin 30 mg twice daily on days 1–7. We retrospectively analyzed the feasibility of GSL and patient outcomes in three medical centers in Taiwan. Results Overall, 49 patients received GSL with a median follow-up of 24.9 months from May 2015 to March 2019. The median patient age was 68 years (range, 47–83 years), with a marginally higher number of females (57.1%). Among the 44 patients who underwent image evaluation, 13 demonstrated a partial response (29.5%) and 17 presented with stable disease (38.6%). The partial response rate and stable disease rate was 26.5% and 34.7%, respectively, in the intent-to-treat analysis. The median time-to-treatment failure was 5.79 months (95% C.I., 2.63–8.94), progression-free survival was 6.94 months (95% C.I., 5.55–8.33), and overall survival time was 11.53 months (95% C.I., 9.94–13.13). For GSL treatment, the most common grade 3 or worse toxicities were anemia (18.3%), neutropenia (6.1%), nausea (4.1%), and mucositis (4.1%). Treatment discontinuation was mostly due to disease progression (65.3%). Conclusions The modified GSL therapy can be a promising and affordable treatment for patients with advanced and metastatic pancreatic cancer in Taiwan. A prospective trial of modified GSL for elderly patients is currently ongoing in Taiwan.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4168-TPS4168
Author(s):  
Laith I. Abushahin ◽  
Anne M. Noonan ◽  
John L. Hays ◽  
Pannaga G. Malalur ◽  
Ashish Manne ◽  
...  

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.


Cureus ◽  
2021 ◽  
Author(s):  
Nedal Bukhari ◽  
Khalda Abdalla ◽  
Fahad Ibnshamsa ◽  
Waleed Alselwi ◽  
Shakir Al-Shakir ◽  
...  

Oncology ◽  
2011 ◽  
Vol 80 (5-6) ◽  
pp. 301-306 ◽  
Author(s):  
Elias Assaf ◽  
Muriel Verlinde-Carvalho ◽  
Catherine Delbaldo ◽  
Julien Grenier ◽  
Zineb Sellam ◽  
...  

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