Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program
, Rianne Brood 1, Diba Latifi 1, Astrid A. Oostvogels 2, Yarne Klaver 2, Miranda Moskie 1, Dana A. Mustafa 3, Reno Debets 2 and Casper H. J. van Eijck 1,*Round 1
Reviewer 1 Report
Haddaoui et al. describe that they conducted a single-center named patient program using TLR-3 agonist rintatolimod and it may improve life expectancies through immunomodulation in pancreatic cancer patients. The treatment has novelty and can be help pancreatic cancer patients to prolong their survival. However, there are several serious concerns.
Major revision:
- Is there the Phase I study in the drug apart from the study? Why can they perform the irregular trial using unapproved drug? Please describe the details.
- Please describe the process how to determine the dose of rintatolimod.
- The ethical approval in the study is unclear. Although they mention the study was a part of the Immune Monitoring in Pancreatic cancer study (MEC-2016-575), that is insufficient. Have they truly obtained the IRB approval? If so, how was the description? The study was not RCT or clinical trial, so it would be skeptical to do persuasive explanation to participants.
- There is no description about drug adverse effects. Please describe them and this is important.
- In Table 2, there is no description about the comparison. What comparisons brought the p values?
- Only the comparisons of immune inflammatory markers among patients administered rintatolimod do not justify the drug induces immunomodulation mechanism. I would suggest to compare immune responses between samples with and without rintatolimod using some controls.
Author Response
Please see the attachment.
Author Response File: 
Author Response.docx
Reviewer 2 Report
The manuscript provides interesting data on a potentially novel therapy of PDAC. I applaud the authors on an innovative treatment strategy leeading to interesting results. My main concern is, though, whether the historical control group was adequately selected. Have the patients also been matched for comorbidities? Could you compare the Charlson comorbidity index or ASA status?
Author Response
Please see attachment.
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
The maniscript has been revised amost appropriately. There is no ANOVA test in Table 2, which still needs to be fixed.
Author Response
Please see the attachment.
Author Response File: Author Response.docx
