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Lung Cancer

Oncotarget | Effects of Metformin and Rapamycin in Pancreatic Cancer [Video]

Oncotarget published this trending research paper on May 26, 2020, entitled, “An exploratory study of metformin with or without rapamycin as maintenance therapy after induction chemotherapy in patients with metastatic pancreatic adenocarcinoma” by researchers from the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD; The Skip Viragh Center for Pancreas Cancer at Johns Hopkins, Baltimore, MD; Virginia Piper Cancer Center at HonorHealth, Scottsdale, AZ; Molecular Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ; Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai City, China; The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD.Abstract:Purpose: Metformin combined with the mTOR inhibitor rapamycin showed potential synergistic anti-tumor activity in preclinical studies in pancreatic ductal adenocarcinoma (PDA). This phase 1b study (NCT02048384) was conducted to evaluate the feasibility and activity of metformin +/– rapamycin in the maintenance setting for unselected patients with metastatic PDA (mPDA) treated with chemotherapy.Materials and Methods: Eligible patients with stable or responding mPDA after ≥ 6 months on chemotherapy were randomized 1:1 to metformin alone (Arm A) or with rapamycin (Arm B), stratified by prior treatment with FOLFIRINOX. Fluorodeoxyglucose (FDG) PET scans and peripheral blood mononuclear cells were obtained for exploratory analyses.Results: 22 subjects (11 per arm) received treatment per protocol. Median PFS/OS were 3.5 and 13.2 months respectively, with 2 year OS rate of 37%; there were no differences between arms. No responses were observed by RECIST; however, decreases in FDG avidity and/or CA19-9 were observed in several long-term survivors. Treatment related adverse events of Grade ≥ 3 occurred in 0% vs 27% of patients in Arm A vs B and were asymptomatic hematologic or electrolyte abnormalities that were not clinically significant. Improved survival was associated with low baseline neutrophil: lymphocyte ratio, baseline lack of assessable disease by PET, and greater expansion of dendritic cells following treatment.Conclusions: Metformin +/– rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival. Further prospective studies are needed to clarify the role of these agents in the maintenance setting and to enhance patient selection for such approaches.Press release – https://www.oncotarget.com/news/pr/an-exploratory-study-of-metformin-and-rapamycin-as-maintenance-therapy/Sign up for free Altmetric alerts about this article – https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27586DOI – https://doi.org/10.18632/oncotarget.27586Full text – https://www.oncotarget.com/article/27586/text/Correspondence to – Dung T. Le – dle@jhmi.edu Keywords – pancreatic cancer, mTOR inhibition, maintenance therapy, metformin, rapamycinAbout OncotargetOncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:SoundCloud – https://soundcloud.com/oncotargetFacebook – https://www.facebook.com/Oncotarget/Twitter – https://twitter.com/oncotargetInstagram – https://www.instagram.com/oncotargetjrnl/YouTube – https://www.youtube.com/c/OncotargetYouTube/LinkedIn – https://www.linkedin.com/company/oncotargetPinterest – https://www.pinterest.com/oncotarget/Reddit – https://www.reddit.com/user/Oncotarget/Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnlsMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957

Categories
Lung Cancer

Oncotarget: An exploratory study of metformin and rapamycin as maintenance therapy [Video]

Volume 11, Number 21 of @Oncotarget reported that eligible patients with stable or responding mPDA after 6 months on chemotherapy were randomized 1:1 to metformin alone or with rapamycin, stratified by prior treatment with FOLFIRINOX. Metformin +/ rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival.Dr. Dung T. Le from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287 said, “Pancreatic ductal adenocarcinoma (PDA) is aggressive cancer with high mortality at all stages and limited treatment options in the advanced setting.”Metformin is an antidiabetic drug in the biguanide class of agents which inhibits mTOR complex 1 primarily through AMP-kinase activation.A synergistic effect of the combination of metformin with rapamycin was suggested by preclinical studies demonstrating enhanced inhibition of mTOR in a pancreatic cancer cell line and better growth inhibition of pancreatic cancer cells in a xenograft tumor model with the combination than either agent alone.Based on this, they conducted an exploratory study of metformin with or without rapamycin in patients with mPDA in the maintenance setting.The Le Research Team concluded in their Oncotarget Research Article, “the administration of metformin with or without rapamycin in patients with mPDA who achieve a response to chemotherapy is well-tolerated and was associated with better than expected overall survival in this study. Additional studies are needed to prospectively evaluate the role of these agents compared to a maintenance chemotherapy or observation only approach.”Sign up for free Altmetric alerts about this articleDOI – https://doi.org/10.18632/oncotarget.27586Full text – https://www.oncotarget.com/article/27586/text/Correspondence to – Dung T. Le – dle@jhmi.eduKeywords – pancreatic cancer, mTOR inhibition, maintenance therapy, metforminAbout OncotargetOncotarget is a biweekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:SoundCloud – https://soundcloud.com/oncotargetFacebook – https://www.facebook.com/Oncotarget/Twitter – https://twitter.com/oncotargetLinkedIn – https://www.linkedin.com/company/oncotargetPinterest – https://www.pinterest.com/oncotarget/Reddit – https://www.reddit.com/user/Oncotarget/Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnlsMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957x105Copyright © 2021 Impact Journals, LLCImpact Journals is a registered trademark of Impact Journals, LLC